Fight Fatigue with Vitamin D

Up to a third of all patients visiting their primary care doctors report feeling fatigue.^1,2

Yet physicians rarely come up with an explanation for it, because there are so many possible causes.^1,2

But there is a common link in many cases: Fatigue is often associated with low vitamin D levels.^3-9

Vitamin D is instrumental in regulating biological processes that have been tied to fatigue, including neurotransmitter balance in the brain, inflammation, and more.⁴

Studies have found that increasing vitamin D intake can help reduce symptoms of fatigue, whether tied to a medical condition or not.^2,10-14

Causes of Fatigue

Fatigue is one of the most common complaints doctors hear in their clinics.^1,2 Its prevalence rises with age.¹

It can refer to mental or emotional lethargy and to physical exhaustion and muscle weakness.

Some medical conditions associated with fatigue include autoimmune conditions, infections, cancer, mental illness, and endocrine disorders.^1,4

Cases may also be associated with sleep disturbances, stress, diet, and environmental factors.

Yet for the large majority of people complaining of fatigue, there is no obvious cause.²

However, although many factors may contribute to fatigue, research has revealed that one vitamin may be a critical factor that ties together many cases: vitamin D.

The Vitamin D Link

Many cases of fatigue, including those without an obvious cause and those tied to a medical condition, are associated with low vitamin D levels.^4,5

For example, fatigue is common in older individuals,^1,3,4,9 as are low vitamin D levels.¹⁵

In this group, studies have found a strong association between both mental and physical fatigue and low levels of vitamin D.^3,4,9 In fact, one study found that the lower the vitamin D levels, the more severe the fatigue.⁹

Low vitamin D is also often found in many medical conditions associated with fatigue. Patients with fibromyalgia, multiple sclerosis, rheumatological diseases, cancer, and neurodegenerative disorders often have low levels or a deficiency of vitamin D.^4,6,7

Even work-related fatigue may correlate with lower vitamin D levels. In one study of 200 female nurses with a high prevalence of fatigue, 89% suffered from vitamin D deficiency.⁸ The researchers concluded that their high rate of fatigue could be attributed to low vitamin D levels.

Low Vitamin D Drives Fatigue

Whether a cause can be identified or not, fatigue is driven by several biological factors.⁴

Many of these can be linked to suboptimal vitamin D levels, including:

• Neurotransmitter imbalances. Mental and emotional fatigue can be related to alterations in the activity of several neurotransmitters in the brain, particularly dopamine and serotonin.⁴ Vitamin D is involved in the synthesis and activity of these and other neurotransmitters.⁴ Deficiency of vitamin D can contribute to imbalances that may lead to fatigue.
• Cellular stress. Vitamin D plays an important role in the body's defenses against oxidative stress. Without sufficient vitamin D, stress and cellular damage worsen, which contributes to chronic fatigue.⁴
• Low klotho. Klotho is an anti-aging protein with various functions.¹⁶ In animal models, blocking klotho significantly shortens lifespan, while increasing its activity extends it. Vitamin D activity helps increase levels of this protein, boosting resistance to cellular stress and associated fatigue.⁴
• Immunity. Fatigue has been tied to aspects of suboptimal immune balance, including increased production of pro-inflammatory compounds.⁴ Vitamin D helps counter these alterations, reducing production of inflammatory compounds and supporting healthy immune balance.^4,5
• Gene expression changes. When adequate levels of vitamin D are available, genes tied to cellular protection, antioxidant defenses, immune function, growth factors, and more are all favorably expressed. This means they are appropriately "turned on or off" in response to the body's needs. This helps minimize contributions to fatigue and maximize cellular health and defense.⁴

Reducing Fatigue

Many adults suffer from inadequate levels of vitamin D. These lower levels have been tied to different forms of age-related chronic disease.¹⁷

As a result, taking oral vitamin D to maintain optimal levels is widely encouraged by physicians.

Boosting vitamin D levels also can result in improvements in fatigue.

In one study, more than 77% of adult patients complaining of fatigue had low vitamin D.² After taking oral vitamin D to normalize levels, fatigue scores improved in all categories, including physical, emotional, and mental fatigue.

Average fatigue scores (the higher the number, the more severe the fatigue) dropped from 31.5 points when the study began to 11 points after vitamin D levels were increased, an improvement of more than 20 points, or 65%. A change of just 4 to 11 points is considered clinically important.¹⁸

In another study, healthy adults with low vitamin D and feelings of fatigue received either a single, large dose of vitamin D or a placebo. In those receiving vitamin D, fatigue scores decreased and 72% reported improvement in their fatigue. The more vitamin D levels rose, the greater the reduction in fatigue.¹³

Several studies have shown that vitamin D intake can also reduce fatigue related to disease. For example, taking vitamin D improved symptoms of fatigue in studies of patients with multiple sclerosis, kidney transplants, and lupus.^10-12,14

Daily oral doses of 5,000-8,000 IU of vitamin D3 can help maintain optimal blood levels to fight fatigue. The 25-hydroxy vitamin D blood test is used to assess and adjust dose. Life Extension considers 50-80 ng/mL of 25-hydroxy vitamin D to be an optimal level.

Summary

Most cases of fatigue have no obvious cause, making them difficult to treat. But they are often associated with low vitamin D levels.

Studies have shown that taking oral vitamin D to increase low vitamin D levels can reduce fatigue in healthy adults and in those with medical conditions associated with fatigue.

If you have any questions on the scientific content of this article, please call a Life Extension Wellness Specialist at 1-866-864-3027.

  

References

1. Maisel P, Baum E, Donner-Banzhoff N. Fatigue as the Chief Complaint-Epidemiology, Causes, Diagnosis, and Treatment. Dtsch Arztebl Int. 2021;118(33-34):566-76.
2. Roy S, Sherman A, Monari-Sparks MJ, et al. Correction of Low Vitamin D Improves Fatigue: Effect of Correction of Low Vitamin D in Fatigue Study (EViDiF Study). N Am J Med Sci. 2014;6(8):396-402.
3. Al-Eisa ES, Alghadir AH, Gabr SA. Correlation between vitamin D levels and muscle fatigue risk factors based on physical activity in healthy older adults. Clin Interv Aging. 2016;11:513-22.
4. Di Molfetta IV, Bordoni L, Gabbianelli R, et al. Vitamin D and Its Role on the Fatigue Mitigation: A Narrative Review. Nutrients. 2024;16(2):221.
5. Hock AD. Review: Vitamin D3 deficiency results in dysfunctions of immunity with severe fatigue and depression in a variety of diseases. In Vivo. 2014;28(1):133-45.
6. Koole JL, Bours MJL, van Roekel EH, et al. Higher Serum Vitamin D Concentrations Are Longitudinally Associated with Better Global Quality of Life and Less Fatigue in Colorectal Cancer Survivors up to 2 Years after Treatment. Cancer Epidemiol Biomarkers Prev. 2020;29(6):1135-44.
7. Martinez-Alonso M, Dusso A, Ariza G, Nabal M. Vitamin D deficiency and its association with fatigue and quality of life in advanced cancer patients under palliative care: A cross-sectional study. Palliat Med. 2016;30(1):89-96.
8. Masoudi Alavi N, Madani M, Sadat Z, et al. Fatigue and Vitamin D Status in Iranian Female Nurses. Glob J Health Sci. 2015;8(6):196-202.
9. Pennisi M, Malaguarnera G, Di Bartolo G, et al. Decrease in Serum Vitamin D Level of Older Patients with Fatigue. Nutrients. 2019;11(10).
10. Beckmann Y, Ture S, Duman SU. Vitamin D deficiency and its association with fatigue and quality of life in multiple sclerosis patients. EPMA J. 2020;11(1):65-72.
11. Han B, Wu X, Guo Y. Improvement of fatigue after vitamin D supplementation in kidney transplant recipients. Medicine (Baltimore). 2017;96(21):e6918.
12. Lima GL, Paupitz J, Aikawa NE, et al. Vitamin D Supplementation in Adolescents and Young Adults With Juvenile Systemic Lupus Erythematosus for Improvement in Disease Activity and Fatigue Scores: A Randomized, Double-Blind, Placebo-Controlled Trial. Arthritis Care Res (Hoboken). 2016;68(1):91-8.
13. Nowak A, Boesch L, Andres E, et al. Effect of vitamin D3 on self-perceived fatigue: A double-blind randomized placebo-controlled trial. Medicine (Baltimore). 2016;95(52):e5353.
14. Ruiz-Irastorza G, Gordo S, Olivares N, et al. Changes in vitamin D levels in patients with systemic lupus erythematosus: Effects on fatigue, disease activity, and damage. Arthritis Care Res (Hoboken). 2010;62(8):1160-5.
15. Wang TY, Wang HW, Jiang MY. Prevalence of vitamin D deficiency and associated risk of all-cause and cause-specific mortality among middle-aged and older adults in the United States. Front Nutr. 2023;10:1163737.
16. Zhou H, Pu S, Zhou H, Guo Y. Klotho as Potential Autophagy Regulator and Therapeutic Target. Front Pharmacol. 2021;12:755366.
17. Zmijewski MA. Vitamin D and Human Health. Int J Mol Sci. 2019;20(1).
18. Chan A, Yo TE, Wang XJ, et al. Minimal Clinically Important Difference of the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) for Fatigue Worsening in Asian Breast Cancer Patients. J Pain Symptom Manage. 2018;55(3):992-7 e2.