Vitamin D also called the sunshine vitamin actually doesn’t work like a vitamin rather it works like a hormone. Vitamin D involves not only bone formation it exerts a wide range of biological effects inside the human body. Directly or indirectly Vitamin D regulates about 200 gene expressions that involve cellular death, reproduction, and differentiation. Details of which yet to be understood. Vitamin D also has inverse relations with markers of inflammation. Common factors like chronic fatigue, body pains, sleep disturbance have a negative impact on the quality of life in modern days. Less exposure to sunlight, most of the time living in shade are also some common factors in today’s life. Can low vitamin D levels be a cause behind them? Is vitamin D deficiency linked with chronic fatigue and body aches?
The perspective on how vitamin D influences human health has changed dramatically based on the finding that the vitamin D receptor (VDR) and the vitamin D activating enzyme 1-α-hydroxylase are expressed in many cell types. VDR a member of the nuclear receptor family binds with the calcitriol or most active form of vitamin D and encodes the nuclear hormone receptor. And thus it involves the mediation of the active form of vitamin D hormone.
Vitamin D pathway
You can find vitamin D in two forms vitamin D3 or cholecalciferol and vitamin D2 or ergocalciferol. Our body can synthesize vitamin D3 in the skin upon exposure to Sunlight with the help of cholesterol. Dietary source of vitamin D3 mainly includes few fatty fish, an animal source like egg yolk, butter, etc. While vitamin D2 comes from plant food like mushroom grown in UV light, fortified foods. You can find vitamin D2 in most fortified food since it is the cheaper form.
Vitamin D binds with a specialized protein called vitamin D binding protein (VDBP) and travels through the blood. Both forms of vitamin D are transported to the liver where they are converted to 25-hydroxy vitamin D or 25(OH)D or calcidiol.
25(OH)D or calcidiol is the major circulating and stored form of vitamin D but biologically inactive and must be converted to the biologically active form 1,25-di-hydroxy-vitamin D or 1,25(OH)2D or calcitriol. In the kidney, an enzyme called 1-α-hydroxylase converts 25(OH)D or calcidiol to the most active form 1,25(OH)2D or calcitriol. And this active form of vitamin D moves through the circulation to various parts of the body and exerts its action. However as mentioned the perception of effects of vitamin D on the human body has changed after finding vitamin D receptor (VDR) and the vitamin D activating enzyme 1-α-hydroxylase are expressed in many cell types such as intestine, pancreas, prostate, and cells of the immune system. (1)
Is vitamin D deficiency linked with chronic fatigue and body aches?
Role of vitamin D in osteoporosis and bone formation
Like every other living tissues, organs of our body, bones also have living cells. So they die and new bone cells form and this death and birth circle go continuous. Through which our body removes old bones through a process called osteoclasts or bone resorption. And on the other hand, new bones are formed through a process called osteoblasts or bone formation. Bone resorption is followed by bone formation and one can’t happen without the other.
In some way, anti-resorptive drugs or medicine prevent the resorption process and show good bone mineral density. But actually, you are preserving the old bones and that can make your bone brittle.
Vitamin D and Bone formation
Calcium and phosphorus are two essential nutrients required for bone formation. Most of us know that vitamin D helps in the absorption of calcium and phosphorus from our intestine and release to the circulation. And actually, 1,25-dihydroxy vitamin D(3) or1,25(OH)(2)D(3), or the active form of vitamin D regulates calcium and phosphorus metabolism, thus become a key-player in bone-formation. (2) That’s why if you have low vitamin D level and you are likely to absorb a lesser amount of calcium and phosphorus. And so that further impair the bone formation process. In other words, vitamin D has a direct co-relation with bone mineral density and people having osteoporosis also have low vitamin D levels. (3,4)
One thing I wish to mention vitamin D helps in the absorption of calcium from your intestine and releases it into circulation. And vitamin K2 places calcium from circulation in right place i.e. in bones and teeth. If you have low vitamin K2 the calcium of your circulation more likely to deposits in your blood vessels rather than bones and teeth.
Read more about with this article Vitamin K2-A crucial vitamin for benefits of heart and bone health
Vitamin D has an inverse relationship with Parathyroid Hormone (PTH)
Vitamin D has a close relationship with Parathyroid Hormone (PTH) that is produced by the parathyroid gland. PTH or Parathyroid Hormone maintain normal calcium levels by acting on the intestine, kidneys, and bones. That means when your blood calcium level becomes low PTH brings it back to the normal. In bones, PTH dissolves calcium and bring calcium into the blood.
Vitamin D has an inverse relationship with PTH. That means when you have a low vitamin D level your PTH level becomes high. (5) Therefore people having vitamin D deficiency produces excess PTH which results in excessive dissolving of calcium from bones. Also if you have low vitamin D level your absorption of calcium from food and release to blood circulation impairs. And thus these processes make bones weak and such individual begins to feel pain. In such a case if you are not testing your PTH and vitamin D level and taking painkiller regularly then you are killing your own health. You need to identify the cause, the root cause.
Investigation of vitamin D level in patients of chronic pain and muscle aches at the university-affiliated clinic in Minneapolis, researchers found nearly all the patients had low D level and many had severe deficiency. (6)
What are the studies
Numbers of large observational studies have found people having vitamin D deficiency also had chronic lower back pain. (7,8)
A study on more than 9000 older women found an association of low vitamin D with back pain. In severity, they had difficulty in perform daily activities. (9) Another controlled study people having lower vitamin D levels had experienced nearly twice bone pain in their legs, ribs or joints compared to those with the normal blood level range. (10)
Vitamin D deficiency and body aches, muscle weakness
In addition, bone formation, vitamin D exerts extra‐skeletal actions while reducing inflammation. Vitamin D and its associated minerals calcium, phosphorus has also roles in muscle function. Through its nuclear receptor (VDR) located throughout the body, including skeletal muscle, vitamin D initiates genomic and nongenomic pathways in regulating multiple actions as well as muscle function. Vitamin D also plays a role in muscle development and deficiency can lead to muscle weakness, falls and sarcopenia. Vitamin D deficiency is also associated with insulin resistance, but this is confounded by obesity or overweight and sedentary lifestyle, indoor living. (16, 11)
The vitamin D receptor of VDR is also present in nerve cells called nociceptors, which sense pain. And deficiency of vitamin D can contribute stimulation of nociceptors and muscular hypersensitivity as well as pain. (12)Several studies had also shown supplementation of vitamin D on deficient can reduce various types of pain including musculoskeletal pain.(13,14,15) In 2018 published study vitamin D appears to play a role in muscle strength, injury prevention, and sports performance. (16)
Vitamin D deficiency and Chronic Fatigue and tiredness
Chronic pain can also lead to fatigue and tiredness. Vitamin D deficiency may contribute to symptoms of sleepiness via inflammatory components, including known sleep-regulating substances. Vitamin D functions as a physiologic regulator of sleep and affects the central nervous system homeostatic sleep pressure. (17, 18) Although exact mechanism yet to be ascertained several studies had found an association of low blood vitamin D level with fatigue as well as low quality of life with daytime sleepiness. Studies suggest that clinicians should consider obtaining vitamin D levels in patients with daytime sleepiness/fatigue, nonspecific musculoskeletal (bones, joints, muscles, tendons, ligaments, or nerves) pain.(18,19)
A double-blind placebo-controlled study on 120 men and women age around 30 years had found D treatment significantly improved fatigue symptoms. (20)
Fibromyalgia is a chronic disorder that causes widespread pain often accompanied by fatigue, depression, sleep disturbance, muscle stiffness, cognitive impairment, digestive problem, etc. A meta-analysis revealed credible evidence that vitamin D can also be a determinant factor for fibromyalgia. (21)
Which Form of Vitamin D
In usual vitamin D comes in two forms vitamin D3(cholecalciferol) and D2(ergocalciferol). Vitamin D from the sun and fatty fish contain vitamin D3 and on the other hand, D2 comes from vegetable sources. As the human body can synthesize vitamin D3, not D2, so D3 can be considered as a more preferred source of vitamin D than vitamin D2. A study also showed vitamin D2 has less than one-third potency of that vitamin D3 has. (22)
Due to the fat-soluble properties of vitamin D, adding a small amount of fat with vitamin D will help you to absorb and process better.
The safe upper limit of vitamin D daily intake is as below: (23)
Vitamin D food sources(23)
Vitamin D and calcium supplements might interfere with calcium channel blocker drug. Calcium channel blocker disrupts the movement of calcium through calcium channels. A high dose of vitamin D can be toxic to health. While symptoms of toxicity are unlikely at daily intakes below 10,000 IU/day depending upon the physical condition of the individual. (23)
Which Testing method?
Usually, two types of vitamin D tests are done through a blood sample, determination 25(OH)D or calcidiol and 1,25-di-hydroxy-vitamin D or1,25(OH)2 D or calcitriol. While both tests can give different results. Testing of 25(OH)D can be taken as a better test over 1,25-dihydroxy-vitamin D or 1,25(OH)2 D test due to the following reasons:
- 25(OH)D form stays in the blood for a much longer period gives better stability.
- PTH stimulates the conversion of 25(OH) D vitamin D to 1,25(OH)2 D. So high PTH level may show false results.
Vitamin D deficiency is incredibly a common deficiency but most are not aware of it. Vitamin D deficiency can severely impact the quality of life as well as make people diseases prone. Fortunately, you can fix it easily. If you consider supplementing with vitamin D3, also consider vitamin K2 as must-have. Other minerals go well with include calcium, magnesium. Also read about why do you need magnesium for relaxing muscle as well as blood vessel and food sources, RDA,
Disclaimer: Information provided here are generalized information for
educational purpose only, not intended to provide one to one health
consultation or replace practice of a qualified practitioner. Different
people may have different health condition and may have different reaction
to the same food. Hence it has been advised to consult with health care
provider before application of any of above guidelines.
Source and References:
1. Barbara Prietl, Gerlies Treiber, Thomas R. Pieber, and Karin Amrein,
Vitamin D and Immune Function, Nutrients. 2013 Jul; 5(7): 2502–2521
2.Baeke F, Takiishi T, Korf H, Gysemans C, Mathieu C.,Vitamin D: modulator
of the immune system, Curr Opin Pharmacol. 2010 Aug;10(4):482-96
3.Heike A. Bischoff-Ferrari, Douglas P. Kiel,et. al.,Dietary Calcium and
Serum 25-Hydroxyvitamin D Status in Relation to BMD Among U.S. Adults,
J Bone Miner Res. 2009 May; 24(5): 935–942
4.Caroline De Cock, Olivier Bruyere, Julien Collette, Jean-YvesReginster,
Vitamin D inadequacy in French osteoporotic and osteopenic women,
Joint Bone Spine,Volume 75, Issue 5, October 2008, Pages 567-572
5.Björkman M, Sorva A, Tilvis R.,Responses of parathyroid hormone to
vitamin D supplementation: a systematic review of clinical trials,
Arch Gerontol Geriatr. 2009 Mar-Apr;48(2):160-6
6.Plotnikoff GA, Quigley JM.,Prevalence of severe hypovitaminosis D in
patients with persistent, nonspecific musculoskeletal pain,
Mayo Clin Proc. 2003 Dec;78(12):1463-70
7.Panwar A, Valupadas C, Veeramalla M, Vishwas HN.,Prevalence of vitamin D
deficiency in chronic and subacute low back pain patients in India: a
triple-arm controlled study,Clin Rheumatol. 2018 May;37(5):1367-1374
8.Ghai B, Bansal D, Kapil G, Kanukula R, Lavudiya S, Sachdeva N.,
High Prevalence of Hypovitaminosis D in Indian Chronic Low Back Patients,
Ghai B, Bansal D, Kapil G, Kanukula R, Lavudiya S, Sachdeva N.,Pain
Physician. 2015 Sep-Oct;18(5):E853-62
9. Ariane Viana de Souza e Silva, Paulo Gustavo Sampaio Lacativa et. al.,
Association of back pain with hypovitaminosis D in postmenopausal women
with low bone mass,BMC Musculoskelet Disord. 2013; 14: 184
10.Heidari B, Shirvani JS, Firouzjahi A, Heidari P, Hajian-Tilaki KO.,
Association between nonspecific skeletal pain and vitamin D deficiency,
Int J Rheum Dis. 2010 Oct;13(4):340-6
11.Christian M. Girgis, Roderick J. Clifton‐Bligh, Nigel Turner, Sue Lynn
Lau, Jenny E. Gunton,Effects of vitamin D in skeletal muscle: falls,
strength, athletic performance and insulin sensitivity,Clinical
Endocrinology (2014), 80, 169–181
12.Sarah E. Tague, Gwenaëlle L. Clarke et. al.,Vitamin D Deficiency
Promotes Skeletal Muscle Hypersensitivity and Sensory Hyperinnervation,
J Neurosci. 2011 Sep 28; 31(39): 13728–13738.
13.Schreuder F, Bernsen RM, van der Wouden JC.,Vitamin D supplementation
for nonspecific musculoskeletal pain in non-Western immigrants: a
randomized controlled trial, Ann Fam Med. 2012 Nov-Dec;10(6):547-55
14.Vehapoglu A, Turel O, Turkmen S, Inal BB, Aksoy T, Ozgurhan G, Ersoy M.,
Are Growing Pains Related to Vitamin D Deficiency? Efficacy of Vitamin D
Therapy for Resolution of Symptoms,Med Princ Pract. 2015;24(4):332-8
15.Le Goaziou MF, Kellou N, Flori M, Perdrix C, Dupraz C, Bodier E,
Souweine G.,Vitamin D supplementation for diffuse musculoskeletal pain:
results of a before-and-after study, Eur J Gen Pract. 2014 Mar;20(1):3-9.
16.Geoffrey Abrams;David Feldman;Marc Safran,Effects of Vitamin D on
keletal Muscle and Athletic Performance, Journal of the American Academy of
Orthopaedic Surgeons, 26(8):278–285, APR 2018
17.McCarty DE, Reddy A, Keigley Q, Kim PY, Marino AA., Vitamin D, race, and
excessive daytime sleepiness,J Clin Sleep Med. 2012 Dec 15;8(6):693-7
18.Kevin Johnson and Maryam Sattar,Vitamin D deficiency and fatigue: an
unusual presentation, Springerplus. 2015; 4: 584
19.David E. McCarty,Resolution of Hypersomnia Following Identification and
Treatment of Vitamin D Deficiency,J Clin Sleep Med. 2010 Dec 15; 6(6): 605–
20.Fornaro., MicheleNowak, Albina; Boesch, Lukas; Andres, Erik; Battegay,
Edouard; Hornemann, Thorsten; Schmid, Christoph; Bischoff-Ferrari, Heike A.
; Suter, Paolo M.; Krayenbuehl, Pierre-Alexandre,Effect of vitamin D3 on
self-perceived fatigue: A double-blind randomized placebo-controlled trial,
Medicine:December 2016 - Volume 95 - Issue 52 -p e5353
21.Atekeh Hadinezhad Makrani, Mahdi Afshari, Marayam Ghajar, Zahra
Forooghi, and Mahmood Moosazadeh,Vitamin D and fibromyalgia: a meta-
analysis,Korean J Pain. 2017 Oct; 30(4): 250–257
22.Armas LA, Hollis BW, Heaney RP.,Vitamin D2 is much less effective than
vitamin D3 in humans, J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91
23. National Institute of Health