The Best Vitamins and Supplements to Fight Fatigue Naturally

Author : Ari Whitten
Medical Reviewer: Evan Hirsch, M.D.

Vitamins for Fatigue


Though eating a healthy, phytonutrient-rich diet, exercising regularly and getting good quality sleep are vitally important for improving energy levels, it is often difficult to do while balancing the demands of life. This is where supplements can play an important role. We don’t believe you should rely on supplements to increase energy or fix health issues but do believe they can play a role in complementing a healthy lifestyle.

A study published in the Journal of the International Society of Sports Nutrition showed that it’s really hard to get all the essential vitamins and minerals you need from food alone. This study analyzed the diets of 70 athletes and every single one was deficient in at least three nutrients. Some diets were missing up to fifteen nutrients! 1 The most common vitamins and minerals lacking in the modern diet are the B vitamins, calcium, potassium, iron, zinc, magnesium, and selenium.

Before supplementing, it is important to find out the cause of your fatigue. Blood tests can help you determine if you have any vitamin or mineral deficiencies. Work with your health care provider to assess your results, decide on a treatment plan for your fatigue and determine the safety and efficacy of supplements you use.

There are many supplements out there that have a lot of hype and anecdotal feedback  but lack scientific evidence, so beware! We will only be focusing here on compounds that have genuine, solid, science-backed studies for supporting energy levels.

Vitamins and Supplements that Fight Fatigue Naturally:


Mitochondrial Membrane Support:


NT-Factor Phospholipid Complex

One of the most powerful compounds for mitochondrial regeneration. NT-Factors is a compound used in lipid replacement therapy, a method of replacing damaged membrane glycerophospholipids that accumulate during aging and in various clinical conditions in order to restore cellular and mitochondrial function. It has been shown to reduce fatigue by a whopping 24–43% in people with chronic fatigue syndrome  2 3 4 5, as well as reduce cancer-associated fatigue and the fatigue effects of cancer therapy by similar amounts, in just a few weeks of use  6 7


A red pigment found in krill and other seafood. Due to its special ability to penetrate inside of cells and incorporate itself inside its mitochondrial membranes, Astaxanthin is known to protect the mitochondria against oxygen radicals, conserve their antioxidant capacity and enhance their energy production efficiency. It is thought to be one of the most effective antioxidants known to man, can increase blood flow  8, reduce the oxidation of LDL 9 and improve cognitive function  10. Astaxanthin also modulates blood glucose 11 and so increases levels of Orexin and hence energy levels. One study showed that Astaxanthin may even have anti-aging properties 12. As astaxanthin is fat soluble it is best taken with a meal containing fats and should be taken either a few hours before or few hours after exercise.

Cofactors in Mitochondrial Energy Production:

Cofactors are compounds that assist with biological chemical reactions in the body. These can be vitamins, minerals or coenzymes that work synergistically with enzymes in the production of ATP (our energy currency) by the mitochondria.


An essential mineral and is considered the second most common deficiency affecting about 70% of the American population. A deficiency of Magnesium increases blood pressure, reduces glucose tolerance, and causes abnormal neural excitations that impair sleep  13. The best food sources of Magnesium are leafy greens, nuts, seeds and cacao. Supplementing with Magnesium can have a calming effect on the body  14 and may improve sleep quality – and better sleep means more energy throughout the day. Magnesium can be taken in pill form (as citrate, gluconate or diglycinate) or rubbed on the body in the form of an oil. Alternatively,  you can relax at the end of the day by soaking in a magnesium-rich Epsom salts bath. Magnesium L-threonate is considered a cognitive enhancer. 15

Coenzyme Q10

Naturally occurring in all cells of the body, although the heart, kidneys and liver have the highest levels. CoQ10 plays a critical role in energy production and in protecting cells from oxidative damage 16. As people with some diseases have reduced levels of this substance, including people who have fibromyalgia 17 18 19,have survived heart attacks or heart failure 20 21, have multiple sclerosis 22 23, are infertile  24 25 26, or suffer migraines 27 28, researchers have been interested in finding out whether CoQ10 supplements might have health benefits. CoQ10 enhances blood flow (through nitric oxide preservation), protects blood vessels, lowers oxidative stress, and boosts vitality in anyone who suffers from fatigue, but especially those people with the aforementioned conditions. Additionally, statin drugs are known to deplete CoQ10 levels  29, so supplementation is mandatory in people taking a statin 30.

Acetyl L-Carnitine (ALCAR)

Acetyl L-Carnitine (ALCAR) is a unique form of the amino acid L-Carnitine that is involved in energy production and mitochondrial biogenesis (the growth and creation of new mitochondria). It is known for boosting energy  31 32 33, alertness and cognitive function  34 35 36 and also improves insulin sensitivity 37, thus indirectly increasing levels of Orexin. L-Carnitine has also be shown to effectively reduce depression 38, prevent neurological decline and chronic fatigue during ageing 39 40 41 42 43 and improve cardiovascular health  44. Incidentally, supplementing with ALCAR often results in fat loss because those taking it tend to become more physically active due to the increased energy and vitality it yields.


A type of simple, five carbon sugar, that our bodies make. It is an essential component of adenosine triphosphate (ATP), which supplies energy to our cells. Normal, healthy tissue can make all the ribose it needs but ATP production is hindered by inadequate Ribose when we are stressed by overexertion. ATP production can drop by as much as 20% after a strenuous workout and may take up to 72 hours to fully recover  45 46. Ribose supplementation may also help people who have suffered from heart disease or stroke  47 48 49. Studies have also shown that D-ribose significantly reduced clinical symptoms in patients suffering from fibromyalgia and chronic fatigue syndrome 50. Ribose cannot be found in food, so supplementing with it can have dramatic results, under the right conditions.


Creatine is among the most well-researched and effective supplements. Athletes, body builders, and military personnel use dietary creatine as an ergogenic aid to boost physical performance in sports involving short bursts of high-intensity muscle activity. Creatine is thought to improve strength, increase lean muscle mass  51 52 53, and help the muscles recover more quickly during exercise. It has also been shown to have neuroprotective and cardioprotective benefits  54 55 and increase cognitive function 56 57. Creatine is most effective when taken immediately after exercise with a meal containing carbohydrates.

Activators of Mitochondrial Biogenesis and Defense:

Vitamins for Fatigue


(Phyllanthus emblica) is also known as the Indian Gooseberry and is used in Ayurvedic medicine to treat many ailments. The health benefits of Amla berry can mostly be attributed to its high whole food vitamin C content, and its impressive antioxidant abilities. Alma has been shown to have antiatherogenic, adaptogenic, cardioprotective, gastroprotective, antianemia, anti hypercholesterolemia, antidiarrheal and neuroprotective properties 58. It may also be useful in the prevention and treatment of cancer 59.


A sulfur-containing amino acid naturally found in animal proteins, including meat, seafood, dairy and eggs. It is essential for cardiovascular function  60 and the development and function of skeletal muscle, the retina, and the brain 61. Through signalling neurotransmitters in the brain, such as GABA and BDNF, it has anti-anxiety and antidepressant effects. It also affects Orexin by modulating and improving glucose sensitivity and glucose control. Eye, skin, endothelial and kidney health can be improved by supplementing with taurine, especially in diabetics. Taurine is also essential for the proper function of mitochondria  62 63.

Alpha Lipoic Acid (ideally R-ALA)

A mitochondrial compound involved in energy metabolism. It is one of the most potent anti-oxidants produced naturally by the body, but also found in a variety of foods and in supplement form. It reduces inflammation  64 65 and thereby directly improves energy levels. ALA can also reduce blood glucose levels when taken with a meal and thus maintain levels of the hormone Orexin, which promotes wakefulness.


Curcumin, a yellow, bio-active compound, known to possess powerful anti-oxidant and anti-inflammatory properties. It can help reduce depression and anxiety, slow cognitive decline with ageing, promote cardiovascular health, reduce the risk of diabetes and alleviate other inflammatory conditions, such as arthritis. Curcumin protects and stabilises mitochondrial membranes and plays a role in mitochondrial biogenesis, thus improving energy levels. It also To improve its bioavailability Curcumin can be taken with piperine (found in high concentrations in black pepper), or as NovaSol®, CurcuWin® (136-fold), or LongVida®. These are the most recommended forms.

Green Tea

Containing ECGC (epigallocatechin-3-gallate), a potent phytochemical with a host of health benefits ranging from cardioprotective  66 67, neuroprotective  68 69 and liver protective to anti-diabetic  70, anti-obesogenic, anti-fatigue and even anti-carcinogenic effects! 71 72 ECGC works synergistically with L-Theanine to reduce anxiety and stress and is overall a very powerful protector of Mitochondria. In a 12-week double-blind trial published in the American Journal of Clinical Nutrition, researchers gave 38 overweight adults, a daily polyphenol supplement, containing 282 milligrams of ECGC and 80 milligrams of Resveratrol (found in grape skins), or a placebo pill. People taking the polyphenol supplement had a highly significant increase in the function of mitochondria in their muscles compared to people given a placebo.

PQQ – Pyrroloquinoline quinone

A redox agent (it reduces and oxidizes), which is  capable of reducing oxidation by working synergistically with Glutathione. It is found naturally in soil and foods such as kiwifruit, as well as in human breast milk. PQQ is known for preventing the development of damaging proteins associated with Parkinson’s disease and can stimulate the release of nerve growth factor cells in the brain 73. It also supports mitochondrial function  74 and mitochondrial biogenesis 75 76.

NAD + regenerators:

NAD + stands for nicotinamide adenine dinucleotide. It is a coenzyme found in all living cells. NAD is used to power metabolism by enabling the mitochondria to convert the food we eat into the energy our body needs to sustain all its functions. It also repairs damaged DNA, fortifies the cells’ defense systems and sets the circadian rhythm. However, the amount of NAD+ in your body naturally falls with age. Lower levels of NAD+ are thought to impair biological functions important to health, which might contribute to age-related diseases. It’s believed that increasing NAD+ through supplementation may improve symptoms and/or delay these conditions.The following supplements help maintain/boost levels of NAD.

Citrus Bioflavonoids

Phytonutrients found in citrus fruit. Hesperidin is the primary bioactive compound in orange peels, alongside naringenin. They are powerful antioxidant and anti-inflammatory molecules 77 78 capable of protecting against several degenerative diseases and particularly brain diseases  79.These effects are mediated, in part, by their ability to prevent mitochondrial dysfunction and oxidative stress 80. Flavonoids are also able to protect endothelial cells against a high glucose induced decrease in NAD+ 81.


A polyphenol found in red wine that is associated with life extension and some of the health benefits of wine consumption  82. It is produced in grape skins, peanuts and some berries, as a defense against toxins. It is a potent antioxidant that can protect against heart disease and insulin resistance  83, while also increasing blood flow (and oxygen and nutrient delivery) to the brain 84. Moreover, unlike other antioxidants that interfere with exercise-induced adaptations  85, resveratrol appears to enhance the physiological benefits of exercise 86 87.


A well known bioflavonoid found in fruits and vegetables, particularly onions and apples. It is a potent antioxidant and anti-inflammatory molecule that is involved in mitochondrial energy production, the protection of mitochondria from oxidative stress and mitochondrial biogenesis.  It is also involved in helping the mitochondria regenerate NAD+, which is vital for energy production.

N-acetyl-Cysteine (NAC)

An immediate precursor to the most potent antioxidant that our body makes, glutathione. NAC also promotes detoxification, and acts directly as a scavenger of free radicals  88. Studies have shown that it can increase muscle performance and minimize muscle fatigue during exercise  89, as well as prevent the appearance of DNA damage, the decrease in mitochondrial respiration, and the loss of cellular levels of NAD+ 90.

Niacin and Nicotinamide

The two major forms of Vitamin B3 that are precursors of NAD+. They are known to boost NAD+ metabolism and stimulate the activity of certain enzymes that have been linked to numerous health benefits, including resistance to weight gain, improved control of blood sugar and cholesterol, reduced nerve damage, and longer lifespan. NAD+ is not bioavailable, meaning it can’t be taken orally and still survive the digestion process, therefore supplementing with its precursors, which do survive digestion, is necessary  91. Of the various precursors of NAD+, nicotinamide is one of the most efficient 92.

Reduce Stress with Adaptogens and Medicinal Mushrooms:

Adaptogens are herbs that support the body’s ability to accommodate varying physical and emotional stresses. As stress can cause very real physical changes in the body, including harming the neurological, endocrine, and immune systems, supplementing with adaptogens can significantly improve mood and energy levels. Research shows adaptogens can combat fatigue, enhance mental performance and ease depression and anxiety  93.

Rhodiola Rosea

An adaptogen used in traditional Chinese medicine. Studies have shown that it very reliably reduces symptoms of fatigue and helps with depression, which is also commonly linked to fatigue  94 95. By increasing dopamine signalling and thereby activating Orexin it increases energy and wakefulness. In addition, studies have shown that it improves cognitive and physical performance and promotes longevity.


One of the most important adaptogenic herbs used in traditional Indian Ayurvedic medicine. It has been found to increase energy by increasing the body’s resilience to physical and mental stress  96. It has also been shown to improve thyroid function  97 and improve physical performance in both sedentary people and athletes. Ashwagandha root extract is the preferred form of supplementation.

Panax Ginseng

A well-known Chinese traditional medicine that has gained recognition in the West during the last decade. It is popularly known to increase libido and appears to be effective for mood, immunity and cognition. In addition, Panax Ginseng modulates and reduces blood glucose, which helps maintain levels of Orexin and thus promotes wakefulness 98. Panax Ginseng has been shown to work synergistically with Gingko Biloba (another Chinese, antioxidant-rich herb used to enhance brain health and treat a variety of conditions).

Reishi Mushrooms

A rare mushroom that grows at the base of deciduous trees. It is known to have numerous health benefits, including boosting the immune system, relieving symptoms of chronic fatigue and even treating cancer 99. It is no surprise then that Reishi is known as the ancient “Mushroom of Immortality”. Regular, small-doses calms the body and may help regulate the body’s natural circadian rhythm. Reishi is also used in herbal medicine as an adaptogen, helping your body adapt to stress and improve energy levels.


A fungus that lives on certain caterpillars in the high mountain regions of China. Known as Himalayan Gold because it is often farmed in the Himalayan plateaus, Cordyceps has long been used in ancient Chinese and Tibetan medicine for curing diarrhea, headache, cough, rheumatism, liver disease, kidney disease, and much more. Clinical studies have shown improvements in the level of fatigue experienced by older adults supplementing with Cordyceps  100. Cordyceps is thought to increase the body’s production of Adenosine Triphosphate (ATP), which is the primary energy carrier of the body. In another study healthy elderly volunteers that were administered with Cordyceps while exercising on stationary bicycles showed significant increases in energy and oxygen carrying capacity (VO2 max)  101. If you are looking to feel less tired or have more energy, adding dried and powdered Cordyceps to your coffee will probably help. Being rich in amino acids, and vitamins like B1, B2, B12, and K, Cordyceps is full of energy-boosting nutrients 102. Again, please be cautious if you take anti-hypertensive or anti-coagulant medication and speak with your health care provider before supplementation.


This is by no means an exhaustive list of supplements that enhance energy. For more information read the article titled “The Top Science-Backed Supplements For Energy Enhancement.”

Supplements can definitely help you stay alert and energized throughout the day but they are no substitute to a solid foundation of regular exercise, adequate, quality sleep and a phytonutrient-rich diet. Supplements are after all supplements, meaning they are supplementary to optimal nutrition and lifestyle habits. There really is no way to supplant a nutritious diet, as foods often contain an array of vitamins, minerals and phytonutrients that work synergistically with one another. This is much more powerful than any single isolated nutrient given in supplement form.

Having said that, you can see that many of the vitamins and supplements listed above have myriad unique benefits, beyond increasing energy, and are worthy compliments to a healthy lifestyle. Talk to your healthcare provider to assess your unique situation before starting any supplement regime.


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Medically Reviewed By Evan Hirsch, M.D.

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