Vitamin D – functions, forms and latest research

There is a lot of information in the media currently about the benefits of vitamin D and the government now recommends that everyone should ensure a minimum intake of 10mcg per day through the year. Vitamin D is considered both a vitamin and a hormone and, in conditions where we have adequate exposure to sunlight, it can be manufactured in the skin.

Unfortunately, due to the use of sun creams, people spending more time indoors and a reduced intake of vitamin D rich foods, the prevalence of vitamin D deficiency is increasing. So, when and how should we supplement vitamin D and can we obtain it from the diet? This blog outlines the synthesis, functions and importance of vitamin D.

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Vitamin D production

When the skin is exposed to UVB radiation (from sunlight) a molecule known as 7-dehydrocholesterol (derived from cholesterol) is converted to cholecalciferol, also known as D3. Cholecalciferol travels to the liver where it is converted to 25-hydroxyvitamin D (25OHD). The kidney then converts 25OHD to 1,25-hydroxyvitamin D (1,25OHD), also known as calcitriol, which possesses hormonal properties and regulates calcium and phosphate balance.

Cholecalciferol or D3 can be obtained directly without the need for UVB radiation either from the diet (sources oily fish, eggs and butter) or via supplementation. D3 supplements are generally from animal sources although vegan sources of D3 can be obtained from lichen.

Another plant based form of vitamin D, known as ergocalciferol or D2, can also be obtained from the diet (rich food sources are mushrooms, fortified soya milk and almond milk) or via supplementation. D2 can also be converted by the liver to 25-hydroxyvitamin D and then to 1, 25-hydroxyvitamin D by the kidneys. The differences between D2 and D3 are discussed later.

Functions

Although the most recognised function of vitamin D is in calcium and phosphate metabolism and therefore in maintaining and supporting bone density, vitamin D is also used therapeutically for many other conditions including diabetes, autoimmune disease, dementia and cardiovascular disease. Some of the links between vitamin D and selected health conditions are discussed below.

Bone

Calcitriol (the active form of vitamin D) plays an essential role in maintaining and supporting adequate bone density and it has been shown that vitamin D deficiency is related to an increased risk of osteoporosis and osteomalacia as well as specifically leading to rickets, particularly in children. This is because the primary effect of vitamin D is enhanced calcium absorption in the small intestine.

When there are low levels of blood calcium, PTH (parathyroid hormone) secretion is increased which stimulates production of 1,25OH2D (calcitriol) in the kidney. Calcitriol interacts with the vitamin D receptor (VDR) in intestinal cells and signals to increase the expression of calcium transporters and calcibindin D and increase ATP dependent Ca2+ pumps, all of which increases calcium absorption. Vitamin D also stimulates the reuptake of calcium from the kidneys, therefore reducing the excretion of calcium.

So vitamin D is responsible for maintaining adequate serum levels of calcium and in doing so it helps to maintain bone density. Serum calcium needs to be regulated within a tight physiological range and if levels fall, then the other action of PTH is to cause the release of calcium and phosphate from bone (i.e. in order to maintain adequate serum calcium and phosphate levels). Thus, vitamin D protects bone from calcium and phosphate loss.

Cardiovascular

Low serum vitamin D levels have been associated with an increased risk of hypertension, atherosclerosis, dyslipidaemia, metabolic syndrome and cardiovascular disease. The precise mechanisms for how vitamin D protects the cardiovascular system remain unclear, however potential hypotheses include:

  • Downregulation of the renin-angiotensin-aldosterone system – this system is involved in increasing blood volume and therefore blood pressure. Therefore, it is suggested that vitamin D reduces hypertension via this downregulation
  • Direct effects on the heart and vasculature
  • Improvement of glycaemic control
  • Downregulation of inflammatory pathways

Dementia

Again, as with many other conditions, the role of vitamin D in cognitive health is not yet completely understood.  A large 2014 study published in Neurology showed people with extremely low blood levels of vitamin D were more than twice as likely to develop Alzheimer’s disease or other types of dementia as those with normal vitamin D levels.

Studies have found that vitamin D has pro-cognitive and neuroprotective functions, including the reduction of hallmarks of Alzheimer’s disease such as amyloid beta and phosphorylated tau. In rats, decline in learning and memory was ameliorated by vitamin D3 supplementation, whereas no improvement was observed in controls.

Mechanisms of action by which vitamin D may be supportive of cognitive health include:

  • Inducing nerve growth factors and neurite outgrowth (observed in embryonic rat hippocampal neurons), i.e. supporting nerve growth
  • Increasing activity of choline acetyltransferase, an enzyme involved in the synthesis of the acetylcholine neurotransmitter (a brain chemical important for in memory)
  • Increasing the clearance of amyloid plaques (this has been observed in vitro)
  • Reducing pro-inflammatory cytokine IL-1β, and increasing the anti-inflammatory cytokine, IL-10

Autoimmune

Epidemiological evidence has shown increased prevalence of several autoimmune diseases, including inflammatory bowel disease, MS, type I diabetes and rheumatoid arthritis at Northern latitudes where sun exposure is reduced; therefore, it has been suggested that vitamin D is protective against autoimmune conditions.

This is likely to be due to anti-inflammatory and immune modulating effects that vitamin D has demonstrated, such as regulating the production of inflammatory cytokines and inhibiting the proliferation of pro-inflammatory cells, both of which are crucial for the development of inflammatory and autoimmune diseases.

  • In a recent study, both forms of vitamin D – 1,25(OH)2D3 and 25(OH)D3 exhibited anti-inflammatory actions by dose-dependently inhibiting lipopolysaccharide induced production of IL-6, and TNFα (pro-inflammatory cytokines) by human monocytes (immune cells).
  • T helper 1 (Th1) is essential for part of the innate immune system, particularly in response to infection. However, the balance of T Helper 1 cells with T Helper 2 cells needs to be tightly regulated. Excess Th1 compared with Th2 for prolonged periods of time, in the absence of acute infection, is known as Th1 dominance and is associated with tissue specific autoimmune disease such as multiple sclerosis or rheumatoid arthritis. Research has shown that D3 can reduce Th1 (T helper 1) dominance.

Diabetes

Additional evidence has strongly suggested that vitamin D plays an important role in modifying the risk of type 2 diabetes, an effect which is likely mediated by an effect of vitamin D on beta cell function, insulin sensitivity and systemic inflammation. Vitamin D has both direct and indirect effects, the latter via regulation of calcium effects on various mechanisms related to the pathophysiology of type 2 diabetes, including pancreatic beta cell dysfunction, impaired insulin action and systemic inflammation.

D3 v D2

There has been some debate as to whether there is a difference between supplementing vitamin D3 (cholecalciferol) or vitamin D2 (ergocalciferol). It appears that vitamin D3 is more effective at increasing levels of 25OHD and therefore calcitriol. Research has also shown that higher serum levels of D2 are associated with lower levels of D3 and therefore a high intake of D2 may reduce availability of D3 and potentially calcitriol. Further studies conclude that D3 is more appropriate to sustain adequate 25OHD levels than D2, therefore it is recommended to obtain vitamin D in the form of D3.

Research comparing D3 to D2

  • A study looking at improvement in myelination and recovery from nerve injury concluded that cholecalciferol (D3) is more efficient than ergocalciferol (D2). When delivered at a high dose (500 IU/kg/day), cholecalciferol induced a significant locomotor and electrophysiological recovery. The study also demonstrated that cholecalciferol increases i) the number of preserved or newly formed axons in the proximal end, ii) the mean axon diameter in the distal end, and iii) neurite myelination in both distal and proximal ends.
  • Overall, D3 is slightly, but significantly, more effective than D2 at increasing serum 25(OH)D.
  • One year of D2 or D3 dosing (1,600 IU daily or 50,000 IU monthly) does not produce toxicity, and 25(OH)D levels of less than 30 ng/ml persist in approximately 20% of individuals.
  • Both D2 and D3 relative to placebo have a beneficial effect on arterial stiffness.
  • A study demonstrated that cystic fibrosis subjects are able to achieve or maintain optimal vitamin D status (>30 ng/ml) with two oral regimens of either D3 or D2 treatment, the former being more efficacious.
  • One report suggests that vitamin D2 should no longer be considered equivalent to vitamin D3 based on differences in their efficacy at raising serum 25-hydroxyvitamin D, diminished binding of vitamin D2 metabolites to vitamin D binding protein in plasma, and a non-physiologic metabolism and shorter shelf life of vitamin D2. Vitamin D2, or ergocalciferol, should not be regarded as a nutrient suitable for supplementation or fortification.


Toxicity

The majority of the population are not obtaining adequate levels of vitamin D, however it is possible to have excessive and therefore toxic levels of vitamin D. The main consequence of this is too high a level of calcium within the blood (hypercalcaemia). However, we would suggest that if taking more than 5000 IU per day for more than 3 months, then vitamin D levels should be checked regularly, especially during the summer months.

An adequate blood level is considered to be above 50 nmol/litre; the scientific literature suggests that a higher level of between 100 to 150 nmol/litre is optimal; levels above 250 nmol/litre are not advised and in this case measures should be taken to lower levels. Please note some laboratories use different units i.e ng/ml rather than nmol/litre quoted here. In this case the optimal range is 40 to 60 ng/ml.

Key Takeaways

  • Vitamin D3 is considered superior, as it is more bio-effective, compared to vitamin D2.
  • Food sources of vitamin D3 include oily fish, eggs and butter. Food sources of vitamin D2 include mushrooms, soya and almond milk. However, it is not possible to obtain adequate vitamin D from diet alone.
  • Vitamin D can be manufactured by the skin when exposed to adequate levels of UV light. Ensuring your forearms are exposed to sunlight for 15 minutes per day during summer months (May-October) between 10am and 2pm can help to build vitamin D levels. Do not allow yourself to redden.
  • Vitamin D deficiency is associated with numerous chronic diseases including auto-immune conditions, cardiovascular disease and dementia.
  • Vitamin D3 is essential for supporting calcium homeostasis and therefore maintaining adequate bone density.
  • The UK government recommends a minimum intake of vitamin D3 10mcg per day (400IU) for the whole population. This means taking a daily supplement that includes vitamin D.

If you have any questions regarding the topics that have been raised, or any other health matters, please do contact me (Helen) by email at any time (helen@cytoplan.co.uk)

Helen Drake and the Cytoplan Editorial Team


Relevant Cytoplan Products

High Potency D3 (Vegan) – 62.5mcg (2500IU) of D3 can be used daily to help improve Vitamin D levels

Kids Vitamin D3 (Vegan) – 15mcg (600IU) per tablet

Vitamin D3 Drops (Vegan) – (2 drops = 5mcg), useful for children or those who struggle to take capsules

Vitamin D3 & K2 (Vegan) – A combination of D3 and K2 (100mcg of each) used to increase levels as required

All Vitamin D in our multivitamin and mineral complexes is in the form of vegan D3


References

Chabas J-F, Stephan D, Marqueste T, et al. Cholecalciferol (Vitamin D3) Improves Myelination and Recovery after Nerve Injury. Scemes E, ed. PLoS ONE. 2013;8(5)

Binkley N, Gemar D, Engelke J, et al. Evaluation of Ergocalciferol or Cholecalciferol Dosing, 1,600 IU Daily or 50,000 IU Monthly in Older Adults. The Journal of Clinical Endocrinology and Metabolism. 2011;96(4):981-988.

Forouhi NG, Menon RK, Sharp SJ, et al. Effects of vitamin D2 or D3 supplementation on glycaemic control and cardiometabolic risk among people at risk of type 2 diabetes: results of a randomized double‐blind placebo‐controlled trial. Diabetes, Obesity & Metabolism. 2016;18(4):392-400.

Khazai NB, Judd SE, Jeng L, et al. Treatment and Prevention of Vitamin D Insufficiency in Cystic Fibrosis Patients: Comparative Efficacy of Ergocalciferol, Cholecalciferol, and UV Light. The Journal of Clinical Endocrinology and Metabolism. 2009;94(6):2037-2043.

Lisa A Houghton and Reinhold Vieth. The case against ergocalciferol (vitamin D2) as a vitamin supplement1,2. Am Jour. Cin. Nut.

Swanson CM, Nielson CM, Shrestha S, et al. Higher 25(OH)D2 Is Associated With Lower 25(OH)D3 and 1,25(OH)2D3. The Journal of Clinical Endocrinology and Metabolism. 2014;99(8):2736-2744. doi:10.1210/jc.2014-1069.

Oliveri B, Mastaglia SR, Brito GM, Seijo M, Keller GA, Somoza J1, Diez RA, Di Girolamo G. Vitamin D3 seems more appropriate than D2 to sustain adequate levels of 25OHD: a pharmacokinetic approach. Eur J Clin Nutr. 2015 Jun;69(6):697-702. doi: 10.1038/ejcn.2015.16.

Garland CF, Garland FC, Gorham ED, et al. The Role of Vitamin D in Cancer Prevention. American Journal of Public Health. 2006;96(2):252-261

www.jpreventionalzheimer.com/1232-vitamin-d-and-dementia.htm

Yin K, Agrawal DK. Vitamin D and inflammatory diseases. Journal of Inflammation Research. 2014;7:69-87.

MITRI J, PITTAS AG. Vitamin D and diabetes. Endocrinology and metabolism clinics of North America. 2014;43(1):205-232.


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