Why is it worthwhile to determine vitamin D level?

Dr Renāte Helda, endocrinologist

Determination of vitamin 25(OH)D in the clinical laboratory continues to be the fastest growing laboratory analysis in recent years in terms of frequency in both the US and other developed countries around the world. The basis for this is information on the results of many new studies, some of which will be mentioned later in this article. This can be checked by anyone, imposing this topic at the Google search box, and being momentarily buried in the mountains of information available. Much of this information is devoted to the topical subject.

Vitamin D deficiency in the population.

Today it is no longer a special novelty that more than 50% of the world’s population suffers from D deficiency. This is reinforced by misconception that vitamin D deficiency is predominantly observed in young children, while adult nutrition and lifestyle provides body with sufficient amount of vitamin D. However, several epidemiological studies in Europe, in Northern Europe, similarly in Asian and African countries show vitamin D deficiency, especially in the elderly age. Unfortunately, in Latvia this problem is more focused on only recently, although it is possible to determine the level of vitamin D in the blood (this analysis is not reimbursed by the state, but it is not too expensive, especially if you take into account the later costs and health problems caused by long-term vitamin D deficiency to a human body).

Vitamin D sources.

In nature vitamin D as provitamin exists in two forms: 1) the plants originate ergocalciferol (vitamin D2) which due to ultraviolet (UV) light synthesizes from ergo sterol and 2) the origin of animal cholecalciferol which is formed in the skin (including in human skin) from 7-dehydrocholesterol. So, because of sunlight, plants, mammals and fish are able to synthesize vitamin D, with the exception of cats whose skin does not contain 7-dehydrocholesterol2. However, for animals and humans to activate vitamin D, two metabolic changes, first of all in the liver, of hydrolysis in position 25 (25(OH)D), and then in the kidneys – 1-a-hydrolysies (1.25 di-hidroxy vitamin D), are required in the kidneys, after which active vitamin D can bind to the vitamin D receptors to participate in gene transcription and regulate ion (Ca/P) homeostasis. 88% of vitamin 25(OH)D circulates with vitamin D binding protein and only 0.03% circulates freely, the rest 25(OH)D binds albumins. Elimination half-life is 2 – 3 weeks1, however, it is dramatically shortened if vitamin D binding proteins are reduced in size3.  The ability to get vitamin D in food is relatively small compared to endogenous synthesis – only 10%, while endogenous – 90%. It also explains the possible deficiency of vitamin D for people who suffer from liver or kidney diseases.

Why is vitamin D deficiency dangerous?

For a long time it was believed that rachitis caused by vitamin D deficiency in children and osteomalacia due to calcium malabsorption in adults are virtually the only manifestation of vitamin D deficiency. However nowadays it has been discovered that vitamin D deficiency can also lead to chronic diseases such as osteoporosis and cancer. It turned out that many tissues have vitamin D receptors and the ability to synthesize a-hydroxylase and can themselves produce vitamin D. In many of these tissues, vitamin D induces “cell differentiation” and monitors cell proliferation. Thus, vitamin D has 2 functional groups4:


The key role of 1.25(OH)2D The decisive role for25(OH) and vitamin D receptors (VDR)
Vitamin D synthesis in response to parathyroid hormone (PTH) level Prevention of many chronic diseases. Protective role for the development of certain malignant diseases (cancer)
Vitamin D reaches the target tissues (bones, small intestine) where their activity occurs The non-endocrine function is possibly dependent on 25(OH)D. Subjects with a low level of 25(OH)D (limited exposure to the sun) are less able to produce sufficient levels of 1.25(OH)D in the tissues to effectively regulate cell proliferation. It is possible that in some pathological conditions (autoimmune disease) a low level of 25(OH)D is associated with VDR dysfunction. Under these conditions, the level of 25(OH)D is high.
Vitamin D monitors PTH secretion with negative feedback (increases Ca outside the cell space)  
Since the endocrine function is controlled by the PTH hormone, it is relatively independent of serum 25(OH)D  



Environment: geographic latitudes (farther from the equator), season (winter) Reduced vitamin D synthesis in the skin
Individual (black race, aging, clothing, protection against sun) Reduced vitamin D synthesis in the skin
Malabsorption/Obesity Reduced bioavailability
Hepatic damage Reduced synthesis of 25(OH)D
Kidney damage Reduced synthesis of 1.25(OH)2D
Drugs: glucocorticoids, anticonvulsants, barbiturates, rifampicin Elevated degradation

Chronic diseases associated with low levels of vitamin D

  1. Bone/muscle system: osteoporosis, prone to falls and fractures, proximal myopathy (muscle/bone pain);
  2. Chronic liver disease: cirrhosis of the liver, primary liver cirrhosis of the liver;
  3. Chronic kidney disease;
  4. Cardiovascular disease: ischemic heart disease, arterial hypertension, peripheral arterial disease;
  5. Breathing system: chronic obstructive pulmonary disease, asthma;
  6. Autoimmune and chronic inflammatory diseases: diabetes mellitus (type 1 and 2), multiple sclerosis, psoriasis, Crohn’s disease, rheumatoid arthritis;
  7. Cancer: colorectal, prostate, breast;
  8. Cognitive functions (difficulties in performing cognitive tests);
  9. Peridontose (periodontitis, teeth loss).

Vitamin D determination markers.

Vitamin D 25(OH)D is a safe indicator for vitamin D which reflects both dietary intake of vitamin D and endogenous synthesis while the 1.25(OH)2D vitamin serum concentration is tightly regulated and usually not dependent on staying in the sun or from the food. Vitamin 1.25(OH)2D has a short elimination half-life (4 ‒ 6 hours) and its circulating amount is approximately 1/1000 of the 25(OH)D (wish half-live of about 5 weeks) circulating amount. The 25(OH)D receptor affinity is about 100 times less than 1.25(OH)2D. It was considered previously that in order to evaluate the amount of circulating 25(OH)D, the PTH level, calcium absorption, bone mineral exchange bone and bone mineral density should be taken into account. However, 25(OH)D winter/summer seasonal variations should be taken into account. Regarding the correlation of PTH level with vitamin D, the PTH level remains stable while the concentration of vitamin D is higher than 30 ng/ml. However, it begins to increase with lower vitamin D concentration (secondary hyperparathyroidism). This process in the body is also affected by age and mobility. For example, in older patients, reduced renal function requires more vitamin D to achieve a higher concentration of 25(OH)D for the prevention of hyperparathyroidism.

The maximum absorption of Ca in the small intestine also occurs when the concentration of vitamin D is 30 ng/ml, while the clinical goals are achievable if the vitamin D level is greater than 40 ng/ml.

Impact of vitamin D deficiency:

  1. Vitamin D and aging.

Vitamin D deficiency is a worldwide problem, and it is especially important among older people. There are several reasons for this:

  • The synthesis of cholecalciferol in the skin after exposure to the sun becomes less effective over the years as the dehydrosterol level 7 decreases in the skin;
  • The increase in fat mass leads to the release of the highest fats soluble vitamin 25(OH)D, which lowers its bioavailability;
  • When the level of vitamin D is low, its 1.25(OH) 2D shape is impaired due to the lack of substrate, which is addition to its age, is associated with a decrease in renal function that affects the conversion of 25(OH) to 25(OH)2D. The active metabolite 1.25(OH)2D acts via the vitamin D receptor (VDR). In aging, the expression of VDR is reduced (leading to vitamin D resistance) in bones, small intestine and muscle tissue.
  1. Vitamin D and PTH.

One of the most important developments is the interaction between vitamin D and PTH, which is also of great clinical significance. Like vitamin D, PTH is subject to seasonal fluctuations, but contrary to vitamin D, its highest level is observed in winter. The most important causes of secondary hyperparathyroidism with aging include: vitamin D deficiency, renal failure and reduced intake of Ca with food.


  • Adversely affects the bone;
  • Promotes muscle protein breakdown,
  • Promotes blood calcification, which can lead to cardiovascular events.

Reduced renal function due to the elimination of hyperparathyroidism in older people requires more vitamin D to produce higher levels of 25(OH)D in human organisms. PTH level for older people with concentration of 25(OH)D is greater than 40 ng/ml is comparable to those of the same PTH in young people with a concentration of 25(OH)D of about 30 ng/ml5. These results are confirmed by the study carried out in Italy, Chianti area6.

Diseases with elevated PTH, primary and secondary hyperparathyroidism, are associated with a higher risk of cardiovascular disease and death. A quite resent ULSAM (Upsala Longitudinal Study of Adult Man) showed that elevated PTH level results in higher cardiovascular mortality7. Relationship of vitamin D deficiency with heart problems is due both to the direct effect of vitamin D on heart cells and the indirect effect on heart disease factors. Thus, vitamin D can affect myocardial contractility, natriuretic hormone secretion, regulation of inflammatory cytokinins and renin genes8. The limited volume of the article does not allow to look in detail at the impact of vitamin D deficiency on all organs and their systems. Therefore, the effect of vitamin D deficiency on insulin secretion, and hence diabetes, breast, colorectal and prostate cancer, as well as cognitive function and overall mortality, remained.

  1. Vitamin D deficiency elimination (preventability).

Vitamin D should be prescribed at least once a year for elderly and postmenopausal women.  In the northern hemisphere, it could be the end of October, when effects of summer solar radiation on vitamin D synthesis are already over. If vitamin D deficiency (which is highly probable) is detected, vitamin D replacement therapy should be started immediately from 1000 to 2000 DV per day to until April until sunlight returns to UV radiation. It is otherwise to patients with impaired renal function who need an active vitamin D such as calcitrol appropriate dose, but these cases are the competence of a nephrologist.


Vitamin D is unique in some way with its many pleiotropic effects, some of which have been discovered recently. Vitamin D deficiently is common not only in children, but also in the adult population, which is still not sufficiently diagnosed and treated, although its detection is quick, easy and not too expensive by means of a laboratory analysis. Replacement therapy for vitamin D deficiency is available at a reasonable price (more expensive are the active ingredients of vitamin D but they are reimbursed for an appropriate patient group. As mentioned in the online publication of Italian authors9, there are several misconceptions about the prevention of vitamin D deficiency:

  • that the only vitamin D function is mineral homeostasis,
  • that 400 DV per day has an adequate amount of vitamin D,
  • that the dose of vitamin D of more than 2000 DV per day is toxic,
  • sunbathing is definitely harmful.