Vitamin D3 (colecalciferol) supplements are quite commonly used medications for vitamin D deficiency by all age groups especially in elderly women and young children. It also used to treat and prevent bone disorders like rickets, osteomalacia. Colecalciferol is the natural precursor of the calcium-regulating hormone calcitriol, which plays an important role in regulating calcium and phosphate levels of body in the bone formation and bone resorption. It is produced in the skin under the influence of UV radiation, promotes calcium uptake in the small intestine and stimulates phosphate transport. It promotes the tubular resorption calcium and phosphate which in turn decreases their elimination from body. It also inhibits the production of parathyroid hormone (PTH) in the parathyroids.

Insomnia is a health issue which involves disruption in sleep both qualitatively (Inability to initiate sleep) and quantitatively (Inability to maintain good sleep time). Chronic insomnia can affect the ability to undertake tasks such as going to work or school.

A potential causal link:

There are some patient forums and blogs where the causal relationship between vitamin D intake and insomnia has been proposed and discussed. As per the WHO newsletter, there were 52 reports [Europe (37 reports), the Americas (12), Asia (2), and Africa (1)] with the combination of adverse drug reaction (Insomnia) and Vitamin D3 in their global safety database, VigiBase. Colecalciferol was the only reported drug in 24 cases and it was the only suspected drug in 34 cases. The most common co-suspect drugs were levothyroxine (5 cases), which may also cause insomnia, hydrocodone/paracetamol (4), and lisinopril (4). In some cases, drug interactions are contributory factors for insomnia. The other adverse reactions reported in these cases were anxiety (10 cases), irritability (9), abdominal pain (8), dizziness (8) and nausea (7), and there were quite a few cases where various skin reactions, gastrointestinal reactions and restlessness were co-reported which might have contributed to Insomnia.

In 21 cases the insomnia resolved when the colecalciferol was withdrawn, and in seven cases the insomnia reappeared when the drug was restarted. There are five well documented cases suggesting a causal link between colecalciferol and insomnia with reasonable temporal relationship (time to onset of reaction) and with no relevant medical history, concomitant medications and other concurrent conditions as contributory factors. In four cases, insomnia got abated when the drug was withdrawn. In one case, insomnia reduced after drug withdrawal. In 3 cases, insomnia appeared again after re-administration of colecalciferol. However, there were no published case reports suggesting this causal link in the literature.

The mechanism of action of vitamin D role in sleep regulation is not well studied. As per recent review article, vitamin D binds to receptors in the brainstem areas involved in regulation of sleep. The cells in this area play an important role in the first stages of sleep and in sleep maintenance.

Further evidence from other studies is required to determine the exact mechanism of action and for establishing the causal relationship of Vitamin D with Insomnia.

References:

WHO Pharmaceuticals Newsletter No.1, 2020. Geneva: World Health Organization; 2020. Licence: CC BY-NC-SA 3.0 IGO

Muscogiuri G, Barrea L, Scannapieco M, Di Somma C, Scacchi M, Aimaretti G, et al. The lullaby of the sun: the role of vitamin D in sleep disturbance. Sleep Med. 2019 Feb 1;54:262-5.

Jiang P, Zhang LH, Cai HL, Li HD, Liu YP, Tang MM, et al. Neurochemical Effects of Chronic Administration of Calcitriol in Rats. Nutrients. 2014; 6(12):6048-59.

Monti JM, Jantos H. The Roles of Dopamine and Serotonin, and of Their Receptors, in Regulating Sleep and Waking. Prog Brain Res. 2008; 172:625-46.

González S, Moreno-Delgado D, Moreno E, Pérez-Capote K, Franco R, Mallol J, et al. (2012) Circadian-Related Heteromerization of Adrenergic and Dopamine D4 Receptors Modulates Melatonin Synthesis and Release in the Pineal Gland. PLoS Biol. 2012;10(6).