Vitamin D3

Supplement 1: Vitamin D3

What is it?

Vitamin D is a fat-soluble vitamin that is naturally present in a few foods and also available as a dietary supplement. Vitamin D3 (cholecalciferol) is used as a dietary supplement when the amount of vitamin D in the diet is not sufficient.

Good sources of Vitamin D

• Cod liver oil

• Trout

• Salmon

• Mushrooms

• Milk

• Sardines

• Egg

• Cheese

• Brocolli

• Carrots

• Almonds

• Banana

• Sunflower seeds

Regimen:

• What: Oral capsule/tablet/sachet

• How much / Dosage: 60,000 IU (RDA = 600 IU; tolerable upper limit = 4,000 IU)

• How to use: Take one capsule/tablet/sachet every week for 8 weeks

Recommended Dietary Allowance (RDA): Average daily level of intake sufficient to meet the nutrient requirements of nearly all (97–98%) healthy individuals; often used to plan nutritionally adequate diets for individuals.¹

How does it work?

A suggested mechanism causing primary dysmenorrhea is the increasing production of prostaglandins in the endometrium. Vitamin D metabolites reduce the production of prostaglandin in the uterine endometrium and restrict its biological activity by affecting prostaglandin receptors in the endometrium.²

Vitamin D also helps control inflammation by blocking a key pathway (NF-κB) that triggers the release of inflammatory substances like IL-1beta, IL-6, TNF-α, and others. These substances normally increase pain and inflammation in the body.

In menstrual cramps, strong uterine contractions are caused by calcium entering muscle cells, which activates a protein (myosin light-chain kinase). Vitamin D helps relax these muscles by reducing calcium-related contractions through its effect on certain calcium channels.³

What is the efficacy?

Methods: A double-blind, randomized, placebo-controlled trial was conducted on female students aged 18 to 32 years with primary dysmenorrhea and vitamin D deficiency (25 [OH]D <30 ng/mL). The participants (n=116) received either 50,000 IU of vitamin D3 (cholecalciferol) or placebo capsules on a weekly basis for eight consecutive weeks. The outcomes were pain intensity (scored 0 to 10), number of days with pain, number of consumed pain-relief medications (per day), and severity of systemic symptoms (fatigue, headache, nausea/vomiting, and diarrhea; total score of 0 to 12).

Results: Compared with baseline, the participants who received vitamin D experienced significant reductions in pain intensity (−1.0 and −1.5 score at weeks 4 and 8, P<0.001), the number of days with pain (−1.0 day at weeks 4 and 8, P<0.001), the number of consumed pain-relief medications (−1.0 at weeks 4 and 8, P<0.001), and systemic symptoms severity (−1.0 score at weeks 4 and 8, P<0.001). No significant improvements were observed in the placebo group in terms of these outcomes.

Conclusion: Vitamin D supplementation in women with primary dysmenorrhea and vitamin D deficiency could improve systemic symptoms and reduce pain intensity, the number of days with pain, and the need for consuming pain-relief medications.⁴

Side-effects:

Short-term effects: Nausea, vomiting, constipation

Long-term effects: Fatigue, weakness, unintentional weight loss, bone pain, Neurological symptoms - confusion, apathy, agitation, irritability, kidney damage.

Toxicity is often linked to serum 25(OH)D levels exceeding 250 nmol/L, with levels above 750 nmol/L considered highly dangerous. The condition can lead to severe outcomes such as tissue calcification and heart issues if not managed promptly.

In conclusion, while vitamin D is vital for maintaining bone health and immune function, care must be taken to avoid excessive intake, especially through supplements. Regular monitoring of serum levels is recommended when using high-dose vitamin D for extended periods.

References

1. Office of Dietary Supplements, National Institutes of Health. Nutrient Recommendations and Databases. [Internet]. Bethesda (MD): National Institutes of Health; [cited 2025 May 20]. Available from: https://ods.od.nih.gov/HealthInformation/nutrientrecommendations.aspx

2. Thota C, Laknaur A, Farmer T, Ladson G, Al-Hendy A, Ismail N. Vitamin D regulates contractile profile in human uterine myometrial cells via NF-κB pathway. Am J Obstet Gynecol. 2014 Apr;210(4):347.e1–10. doi:10.1016/j.ajog.2013.12.020.

3. Chen YC, Chiang YF, Lin YJ, Huang KC, Chen HY, Hamdy NM, Huang TC, Chang HY, Shieh TM, Huang YJ, Hsia SM. Effect of vitamin D supplementation on primary dysmenorrhea: A systematic review and meta-analysis of randomized clinical trials. Nutrients. 2023 Jun 21;15(13):2830.

1. Rahnemaei FA, Gholamrezaei A, Afrakhteh M, Zayeri F, Vafa MR, Rashidi A, Ozgoli G. Vitamin D supplementation for primary dysmenorrhea: a double-blind, randomized, placebo-controlled trial. Obstet Gynecol Sci. 2021;64(4):353–63. doi:10.5468/ogs.20316.