‘Vitamin D’: One vitamin, many claims!

Vinoth Rajendran*

Clinical Pharmacist-CST, Kauvery Hospitals, India

*Correspondence: Tel.: +91 94873 87680; email: clinical.cst@kauveryhospital.com

Abstract

The relationship between vitamin D and chronic disease-related clinical outcomes is controversial. In recent times, many benefits from the administration of vitamin D in various clinical settings have been claimed, starting with claims of miraculous recovery from severe and critical COVID-19 in early 2020. The recent reports of such claims were compiled and examined. Vitamin D deficiency is widespread and linked to a variety of disorders. Several studies have looked into the significance of vitamin D supplementation in many of these contexts. However, not all of them found it to be beneficial.

Keywords: Vitamin D; Covid 19; Cancer; Depression; Heart disease.

Background

“Sunshine in a bottle”, there have been long-standing claims that vitamin D brings a wide range of benefits. Vitamin D is a fat-soluble vitamin that belongs to the vitamin D family, which includes (vitamin D1), Ergocalciferol (vitamin D2), and Cholecalciferol (vitamin D3). Vitamin D plays a major role in our body – it promotes calcium absorption and phosphorus, and its deficiency leads to rickets in children and osteomalacia in adults.

In the United States, Vitamin D deficiency is defined as blood calcidiol (25 OH) levels less than 50 nmol/L. Low serum calcidiol levels have been associated with a greater risk for a number of disorders including renal, dermatological, cardiovascular, autoimmune disease, infections, and cancer.

Recently, emphasis has shifted to non-traditional effects of vitamin D reduction in the risk of autoimmune illnesses (including type 1 diabetes), multiple sclerosis (MS), and systemic lupus erythematosus) and immune-mediated diseases such as inflammatory bowel disease (IBD), autoimmune encephalomyelitis (EAM).

Does vitamin D have the potential to combat illness?

Evidence from clinical trials shows that vitamin D may potentially play a role in the following:

Reducing the risk of heart disease

A randomised controlled study revealed that taking 400 IU of vitamin D and calcium for 8 weeks dramatically decreased systolic blood pressure by 9%. The study revealed CVD risk declined significantly with rising doses until levelling out at roughly 50 nmol/L and also similar for blood pressure (BP). In contrast, many smaller trials done found no impact of vitamin D supplementation on blood pressure. In a European trial, people receiving 800 IU of vitamin D had no better cardiovascular survival than controls [1]. Vitamin D deficiency has been connected to cardiovascular disease. However, it is questionable whether vitamin D deficiency leads to cardiovascular disease.

Vitamin D deficiency linked to fatty liver

The researchers assessed 25(OH)D they found severe vitamin D deficiency is positively associated with non-alcoholic fatty liver disease (NAFLD). When compared to men, women are at more risk.

Vitamin D in cirrhosis patients with spontaneous bacterial peritonitis

In one study, patients received a loading dose 300000 IU of Vitamin D3, followed by a maintenance 800 IU/d orally, with 1000 mg oral calcium; supplementation increased survival rate [2].

Vitamin D and type 2 diabetes

A meta-analysis observed that people with greater 25(OH)D levels had a 38% lower chance of having T2D. A trial evaluated the efficacy of ergocalciferol 50.000 IU/week and placebo: there were no changes in insulin secretion or insulin sensitivity [3].

Magnesium intake might affect serum vitamin D and T2DM risk

The researchers analysed data from the National Health and Nutrition Examination Survey (NHANES) 2007 to 2014; they found evidence of interaction between vitamin D levels and magnesium intake on decreasing the incidence of T2DM.

Vitamin D in COVID-19

Although studies are mixed, low vitamin D levels contribute to acute respiratory distress syndrome, with the substantial increase in the risk of death.

Vitamin D could potentially benefit migraine

A meta-analysis suggested benefits in treating migraine. The study indicated that vitamin D supplementation might reduce headache episodes per month, headache days per month.

Vitamin D fails to improve mental health in early psychosis: DFEND trial

One randomised controlled trial looked at vitamin D supplementation in adults with psychosis, and 14 000 IU weekly for 8 weeks showed no advantage in resistant schizophrenia. According to the findings of a new study, there was no correlation between vitamin D supplementation and mental health or metabolic outcomes [4].

Cancer and vitamin D supplementation studies

A meta-analysis indicated that vitamin D supplementation is linked with a considerably decreased risk of cancer death. The study shows that, weekly high-dose calcitriol and docetaxel (Rocaltrol (0.5 mcg/kg) on day 1 + docetaxel (36 mg/m2 ) on day 2, repeated weekly for 6 weeks was effective in 37 prostate cancer patients. Analogues like Seocalcitol, Inecalcit, Calcipotriol, and Paricalcitol were reported effective in managing different types of cancers [5].

General dosing and indications for vitamin D

Cholecalciferol

  1. 50,000 IU orally once weekly for 8 weeks or 6000 IU once daily for 8 weeks to achieve a 25-hydroxyvitamin D level greater than 30 nm/mL; follow with a maintenance dose of 1500 to 2000 IU/day.
  2. Obesity, malabsorption syndromes, or concomitant use of medications affecting vitamin D metabolism: 6000 to 10,000 IU orally once daily for 8 weeks, maintenance dose of 3000 to 6000 IU/day.

Prophylaxis

  1. Oral solution, 1000 IU /drop; 1 drop orally daily.
  2. Older than 50 years: 800 to 1000 IU orally every day; up to 10,000 IU orally every day is safe for 5 months (off-label dosage).
  3. Inadequate sun exposure: 800 to 1000 IU orally every day; up to 10,000 IU orally every day is safe for 5 months (off-label dosage)
  4. Chronic kidney disease, stages 2 to 5: 1000 IU orally every day; serum phosphate should be controlled (off-label dosage).
  5. Granulomatous disorders and some lymphomas: 400 IU orally every day.
  6. Primary or tertiary hyperparathyroidism: 800 to 1000 IU orally every day (off-label dosage).
  7. Malabsorption syndromes: Up to 10,000 IU orally every day is safe for 5 months (off-label dosage).
  8. Nephrotic syndrome: 1000 to 2000 IU orally every day (off-label dosage).
  9. Obesity: 1000 to 2000 IU orally every day (off-label dosage).
  10. Pregnant or lactating: 1000 to 2000 IU orally every day; up to 4000 IU orally every day is safe for 5 months (off-label dosage).

Ergocalciferol

  1. Familial x-linked hypophosphatemic vitamin D refractory rickets: 12,000 to 500,000 IU orally daily.
  2. Hypoparathyroidism: 50,000 to 200,000 IU orally once daily (plus calcium lactate 4 g, 6 times daily)

Vitamin D deficiency

  1. Older than 50 years, Primary or tertiary hyperparathyroidism, Chronic kidney disease, stages 2 and 3, Pregnant or lactating; 50,000 IU orally once weekly for 8 weeks; maintenance dose of 50,000 IU once every 2 or 4 weeks. May repeat the 8-week course if 25-hydroxyvitamin D is less than 30 ng/ml.

Nephrotic syndrome

  1. Obesity:50,000 IU orally twice weekly for 8 to 12 weeks; 50,000 IU once every 2 or 4 weeks [6,7].

Conclusion

Vitamin D deficiency is widespread and linked to a variety of disorders. Several research studies have looked into the significance of vitamin D supplementation; however, not all of them found it to be beneficial. The treatment of vitamin D insufficiency in healthy people must be tailored, and dosages should be appropriate to maintain blood 25(OH)D levels between 40-70 ng/mL. We may soon have a better knowledge of their function in a variety of chronic diseases and many more claims are on the way.

References

  1. Trivedi DP, Doll R, Khaw KT. Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. BMJ. 2003;326:469.
  2. Mohamed AA, Al-Karmalawy AA, El-Kholy AA, et al. Effect of vitamin D supplementation in patients with liver cirrhosis having spontaneous bacterial peritonitis: a randomized controlled study. Eur Rev Med Pharmacol Sci. 2021;(22):6908-19.
  3. Mitchell DM, Leder BZ, Cagliero E, et al. Insulin secretion and sensitivity in healthy adults with low vitamin D are not affected by high-dose ergocalciferol administration: a randomized controlled trial. Am J Clin Nutr. 2015;102: 385-92.
  4. Krivoy A, Onn R, Vilner Y, et al. Vitamin D supplementation in chronic schizophrenia patients treated with clozapine: a randomized, double-blind, placebocontrolled clinical trial. EbioMedicine. 2017;26:138-45.
  5. Easty DJ, Farr CJ, Hennessy BT. New roles for vitamin d superagonists: From COVID to cancer. Front Endocrinol. 2021;12:644298.
  6. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266-81.
  7. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Endocrine Society. Evaluation, treatment, and prevention of vitamin D deficiency: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911-30.

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Vinoth-Rajendran

Vinoth Rajendran

Clinical Pharmacist-CST

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