Vitamin D

Vitamin D

by David Archibald

5 February 2023


Plants, animals and funghi all have a form of vitamin D. All produce it by exposure to ultraviolet radiation from the Sun, specifically UVB.

The amount of Vitamin D a human will produce per day under optimum conditions is about 0.25 milligrams in about half an hour of sun exposure. Staying out in the sun longer doesn’t produce any more. The units people are familiar with in vitamin D are International Units (IU). There are 40,000 IU in a milligram so average daily production under ideal conditions is about 10,000 IU.

In humans, vitamin D is produced in the skin by UVB acting on 7-dehydrocholesterol. The production of vitamin D in the skin is not time constrained; a patch of skin will produce vitamin D until all its 7-dehydrocholesterol is consumed in conversion.

Vitamin D acts through vitamin D receptors on the cell surface and also on the nucleus. The main function of vitamin D is the maintenance and regulation of calcium levels in the body. It is necessary for the development of a healthy skeleton. Vitamin D deficiency results in higher rates of hypertension, autoimmune diseases, diabetes, cancer, and viral infections. In fact, some viruses have evolved to suppress the vitamin D receptor. In turn, vitamin D receptors can be activated by some plant molecules, including quercetin and resveratrol.

Vitamin D can be far more efficient than higher level treatments. For example, in a 2014 study of flu vaccinations1, it was found that 71 people would need to be vaccinated to prevent one case of influenza which translates to a 1.4% response rate. In contrast, a 2010 study of 334 school-aged children found that, compared to a placebo, 1,200 IU a day of vitamin D over four months achieved a risk reduction of 7.8% against the flu virus.

Vitamin D has a wholesale price of US$21/kg, now equating to A$30/kg. A daily dose of 10,000 IU is 0.25 of a milligram. So a gram of vitamin D would provide 4,000 doses at that rate at a cost of A$0.0075 per dose.


Figure 1: UV levels in summer and winter of Melbourne in 2022


Optimum Level

People living in the tropics normally have a vitamin D blood level in the range of 40 to 80 ng/ml. A nanogram is one billionth of a gram. The highest recorded individual blood level obtained from sunshine was from a farmer in Puerto Rico with a level of 86 ng/ml1.  The highest recorded individual vitamin D level achieved from artificial ultraviolet light treatment sessions was 105 ng/ml2.

There is another sign that a vitamin D level below 40 ng/ml is suboptimal. This is the parathyroid hormone level in the blood, which begins to rise steadily once the vitamin D level falls below 25 ng/ml. Parathyroid hormone’s role is solely in the regulation of the blood calcium level. It seems that the body makes more of this hormone, that it can make itself, to ensure that some vitamin D is available for other roles in the body when the vitamin D level is suboptimal.


Figure 2: Vitamin D blood levels and sufficiency


Vitamin D has a half life in the bloodstream of 15 days3. Vitamin D is lipophilic and some is stored in fat. In a study4 of Romanian nursing home inmates given 125 µg (5,000 IU) of vitamin D daily in bread, their normal average vitamin D level prior to the experiment was 11 ng/ml. After one year of supplementation their average vitamin D level had risen to 48 ng/ml. A year after supplementation finished, their vitamin D level had fallen to 25 ng/ml. After two years and their average vitamin D level had fallen to its baseline level.


Figure 3: Romanian nursing home study


The body’s uptake of vitamin D from supplementation is non-linear, and is affected by body weight. Uptake drops off as 70 ng/ml is approached, as shown in the following graphic:


Figure 4: Vitamin D dosing and blood level response


Vitamin D and Cancer

Vitamin D’s other roles include suppressing cancer. Because vitamin D is known to participate in cell cycle regulation, cellular proliferation and apoptosis, angiogenesis, and molecular cell signaling, it follows that this metabolite is involved in the development and progression of numerous cancers.

In a study of women in Taiwan, it was found that those with a dietary intake of vitamin D of more than 5 µg (200 IU) had a 48% lower incidence of breast cancer than those with an intake of less than 2 µg (80 IU) per day1.

In prostate cancer, a meta-analysis found that every eight ng/ml increase in circulating vitamin D level decreased all-cause mortality by 9% in a nonlinear relationship2. The effect is most pronounced below a vitamin D blood concentration of 40 ng/ml. All-cause mortality is the red line in the following graph:


Figure 5: Vitamin D level and prostate cancer mortality


Most Australians have a blood vitamin D concentration of about 25 ng/ml. If the blood concentration was doubled to 50 ng/ml, the prostate cancer rate would fall 45% from the rate at 25 ng/ml.

In some pancreatic cancer cell lines, the vitamin D receptor is present at up to three times the level of that of normal pancreatic cells3. The implication of this is that the evolutionary response to cancer in some organs is to aid a cancer cell’s uptake of vitamin D, which in turn will restore the apoptotic process to some extent. This is similar to the fact that some cancer cell lines over-express β-glucuronidase relative to normal tissue. β-glucuronidase cleaves the sugar molecule from plant molecules that have been processed in the liver for excretion by the kidneys. This allows the plant molecule to regain its binding activity to receptors in the apoptotic cascade of the caspases.

In a study of the vitamin D’s effect on melanoma, a melanoma cell line was compared to a cervical and a breast cancer cell line with the following results4:


Cancer Type Cell Line IC50
Melanoma B16-F-10 101.7 ng/ml (24 hours)
Cervical HeLa 79.2 ng/ml (24 hours)
Breast MCF-7 79.2 ng/ml (24 hours)


The significance of these results is that they are achievable with a high rate of vitamin D supplementation. An in vitro result doesn’t necessarily mean that the same result (half the cancer cells dead in 24 hours) will be achieved in humans, but at least it indicates that vitamin D’s effect is significant and worth pursuing. These levels corroborate the result found in the prostate cancer meta-analyis quoted earlier.

In the field of breast cancer, a British case-control study5 found that women with vitamin D serum concentrations of greater than 52 ng/ml had a significant 50% lower risk of breast cancer than those with levels of less than 13 ng/ml. This result was corroborated by a pooled analysis that found that a level of vitamin D above 60 ng/ml resulted in an 80% lower incidence of breast cancer over four years5.


Figure 6: Vitamin D blood level and breast cancer incidence


In colon cancer, a big study6 following up 25,620 volunteers between 1975 and 1983 found that the risk of colon cancer was reduced by 75% in the third quintile (27-32 ng/ml) and by 80% in the fourth quintile (33-41 ng/ml) of serum vitamin D. The risk of getting colon cancer decreased three-fold in people with a serum vitamin D concentration of 20 ng/ml or more.

In an Italian study7 of squamous cell carcinoma of the esophagus, those in the highest third of vitamin D intake, corresponding to an intake of more than 3.5 μg (140 IU) /day, had risk reductions of ∼40% for esophageal cancer and 25% for oral and pharyngeal cancers. The inverse association of both cancers with vitamin D intake was most pronounced among those who were heavy current smokers (≥20 cigarettes/day) and heavy consumers of alcohol (≥7 drinks/day).

A case report in pancretic cancer described a female PC patient who errantly took a high doses of vitamin D at 50,000 U daily for a 10-month period, achieving a serum 25(OH)D level of >150 ng/mL, with no appreciable side effects. Although it is uncertain whether it was related to vitamin D supplementation, her disease was stable for the 8 months she was off conventional treatment8.

Supplementation Rate

In people with a normal ability to absorb vitamin D, each 1 µg per day (40 IU per day) will raise the blood concentration of vitamin D approximately 0.3 to 0.4 ng/ml1. The largest rate of increase is seen in those starting with low levels with the rate of increase declining as the blood concentration reaches 40 ng/ml. This effect is illustrated by an online anecdote:

My vitamin D level on initial testing was very deficient at 25.5 ng/ml. With total daily intake of 9,600 IU, it still took a year before I finally arrived in the 60 to 75 ng/ml range. With a daily total intake of 6,600 IU I have been able to remain within that range.

A physiological, safe dose of vitamin D is about 10,000 IU/day. This is the amount our own body produces when exposed to 20-30 minutes to the mid-day sun. With this daily dose, no precautions or medical supervision is necessary. It is worth noting that the IOM (Institute of Medicine) indicates that 10,000 IU/day is considered the “NOAEL”- No Observed Adverse Effect Level.

A protocol developed in Brazil, the Coimbra Protocol, uses high doses of vitamin D to treat autoimmune diseases2. A 2013 analysis3 of 319 patients treated under that protocol found that the average daily dose of vitamin D used was 35,291 IU for up to 3.5 years. All these patients remained in the normal range for total serum calcium (2.4 ± 0.1 mmol/L), serum creatinine (0.8 ± 0.2 mg/dL), serum cystatin C (0.88 ± 0.19 mg/L), serum TSH (1.8 ± 1 mIU/L), and for 24 h urinary calcium secretion (6.9 ± 3.3 mmol/24 h). A very weak relationship between the dosage of oral vitamin D3 and the subsequent calcium levels was found.

Vitamin D regulates its synthesis by a robust negative feedback mechanism.

Two cases of overdosing vitamin D due to formulating errors illustrate the inherent safety of vitamin D. A four year old girl with cystic fibrosis was prescribed a daily dose that included 800 IU of vitamin D4. Two and a half months later she presented at hospital with weight loss and other problems. It was found that her daily dose of vitamin D was 8,000,000 IU which is ten thousand times higher than her prescribed dose. Her starting level of serum vitamin D was measured at 30 ng/ml and in hospital at 1,675 ng/ml. In another formulating error5, a patient prescribed 2,000 IU per day was instead given capsules containing 4,000,000 IU per day, two thousand times the prescribed dose. After he presented with worsening of renal function and hypercalcemia and was found to have a serum vitamin D level of 226 ng/ml. The fact that people can survive vitamin D dosing at 2,000 and 10,000 times the prescribed dose speaks volumes to the inherent safety of vitamin D.

Vitamin D and Covid

Vitamin D is the largest regulator of activity in the immune system. When there is a deficiency of vitamin D, the patient can’t regulate, which means stimulate or reduce, the activity of thousands of biological functions inside the cells of the immune system.

Vitamin D is strongly antiviral and a number of viruses have evolved to suppress the vitamin D receptors on cells. This includes the Epstein-Barr virus1. Covid also responds to vitamin D. Early in the pandemic it was noted that covid incidence correlated with the serum vitamin D level2:


Level of Vitamin D Covid Incidence
<20 ng/mL 12.5%
30-34 ng/ml 8.1%
 ≥ 55 ng/mL 5.9%


There are plant molecules that are vitamin D receptor activitators, including resveratrol and quercetin. It may be that after a bout of covid, the vitamin D receptors will need to be reactivated using one of these molecules.


It is accepted that children have stronger immune systems than adults. This could be due to children spending more time outside playing and thus generating vitamin D. It is known that dog owners are healthier than those who don’t own dogs. Apart from a companion animal effect, this is likely to due to dogs knowing that they need to go for a walk for 20 minutes or so each day. Cats don’t provide a similar health benefit to their owners. Vitamin D supplementation at at least 10,000 IU per day has the potential to halve the disease burden in Australia.


David Archibald is the author of The Anticancer Garden in Australia




  1. Demicheli V, Jefferson T, Al-Ansary LA, et al. Vaccines to prevent influenza in healthy adults (review). Cochrane Database of Systematic Reviews 2014;Issue 3.
  2. Urashima M, Segawa T, Okazaki M, et al. Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren. Am J Clin Nutr 2010;91(5):1255-1260.

Optimum Level

  1. Haddock, L.; Corcino, J.; Vazquez, M.D. 25 OHD serum level in the normal Puerto Rican population and in subject with tropical sprue and parathyroid disease. Puerto Rico Health Sci. J. 1982, 1, 85–91.
  2. Krause, R.; Buhring, M.; Hopfenmuller, W.; Holick, M.F.; Sharma, A.M. Ultraviolet B and blood pressure. Lancet 1998, 352, 709–710.
  3. Jones, Glenville, 2008, “Pharmacokinetics of vitamin D toxicity” American Journal of Clinical Nutrition, Aug;88(2):582S-586S.
  4. Costan, A.R., C. Vulpoi, V. Mocanu, 2014, “Vitamin D fortified bread improves pain and physical function domains of quality of life in nursing home residents” Journal of Medicinal Food, May;17(5):625-31.

Vitamin D and Cancer

  1. Meei-Shyuan Lee, Yi-Chen Huang, Mark L Wahlqvist, Tsai-Yi Wu, Yu-Ching Chou, Mei-Hsuan Wu, Jyh-Cherng Yu, Chien-An Sun, 2010, “Vitamin D decreases risk of breast cancer in premenopausal women of normal weight in subtropical Taiwan” Journal of Epidemiology, 21(2):87-94.
  2. Zhen-yu Song1, Qiuming Yao2, Zhiyuan Zhuo1, Zhe Ma1, and Gang Chen. 2018, “Circulating vitamin D level and mortality in prostate cancer patients: a dose–response meta-analysis” Endocrine Connections, Volume 7: Issue 12.
  3. Elin Albrechtsson, Tord Jonsson, Sebastian Möller, Mattias Höglund, Bodil Ohlsson, Jan Axelson, 2003, “Vitamin D receptor is expressed in pancreatic cancer cells and a vitamin D3 analogue decreases cell number” Pancreatology, 3(1):41-6.
  4. Sutedja, E.K. et al, 2021, “Calcitriol Inhibits Proliferation and Potentially Induces Apoptosis in B16-F10 Cells” Medical Science Monitor Basic Research, 28: e935139.
  5. Lowe C., M. Guy, J.L. Mansi, et al, 2005, “Plasma 25-hydroxy vitamin D concentrations, vitamin D receptor genotype and breast cancer risk in a UK Caucasian population” Eur J Cancer, 41:1164–9.
  6. 5A McDonnell SL, Baggerly CA, French CB, Baggerly LL, Garland CF, et al, 2018 “ Breast cancer risk markedly lower with serum 25-hydroxyvitamin D concentrations ≥60 vs &lt;20 ng/ml (150 vs 50 nmol/L): Pooled analysis of two randomized trials and a prospective cohort.” PLOS ONE 13(6): e0199265.
  7. Garland, C.F., G.W. Comstock, F.C. Garland et al, 1989, “Serum 25-hydroxyvitamin D and colon cancer: eight-year prospective study” Lancet; 2:1176-8.
  8. Lipworth, L., M. Rossi, J.K. McLaughlin, et al, 2009, “Dietary vitamin D and cancers of the oral cavity and esophagus” Annals of Oncology, 20:1576-81.
  9. Cannon, T.L., J. Ford, D. Hester, D.L. Trump, 2016, “The Incidental Use of High-Dose Vitamin D3 in Pancreatic Cancer” Case Reports in Pancreatic Cancer, Volume 2.1.

Supplementation Rate

  1. Dawson-Hughes, B., 2010, “Treatment of Vitamin D Deficient States” Wolters Kluwer Health Website.
  2. Coimbra Protocol website
  3. Amon, U., R. Yaguboglu, M. Ennis, M. Holick and J.Amon, 2022, “Safety Data in Patients with Autoimmune Diseases during Treatment with High Doses of Vitamin D3 According to the Coimbra Protocol” Nutrients, 14(8), 1575.
  4. Nauwynck, E. et al, 2022, “Everything in excess is opposed to nature, even vitamin D: a case report” Endocrinology, Diabetes and Metabolism Case Reports, volume 2022, Issue 1.
  5. Marins, T.A. et al, 2014, “Vitamin D intoxication: case report” Einstein, 12(2): 242–244.

Vitamin D and Covid

  1. Yenamandra, S. P., 2010, “Epstein-Barr virus encoded EBNA-3 binds to vitamin D receptor and blocks activation of its target genes” Cellular and Molecular Life Sciences, DOI: 10.1007/s00018-010-0441-4.
  2. Uliveiri, F.B. et al, 2021, “Vitamin D in the Covid-19 era: a review with recommendations from a G.I.O.S.E.G. expert panel” Endocrine, 72:597–603.
  3. Bilezekian, J.P. et al, 2020, “Vitamin D and Covid-19” Mechanisms in Endocrinology, 183.5, R133-R147.
  4. Borsche, L., B. Glauner, J. von Mendel, 2021, “COVID-19 Mortality Risk Correlates Inversely with Vitamin D3 Status, and a Mortality Rate Close to Zero Could Theoretically Be Achieved at 50 ng/mL 25(OH)D3: Results of a Systematic Review and Meta-Analysis” Nutrients, 13, 3596.
  5. Barrea, L. et al, 2022, “Vitamin D: A Role Also in Long COVID-19?” Nutrients, 14, 1625.
  6. Seal, K.H., D. Bertenthal, E. Carey, C. Grunfeld, D.D. Bikle, C.M. Lu, 2022, “Association of Vitamin D Status and COVID-19-Related Hospitalization and Mortality” J. Gen. Intern. Med., 37, 853–861.