Vitamin D3

Cholecalciferol

Vitamin D has long been considered only a substance that is necessary for the metabolism of calcium in the body. However, it has gradually become clear that a deficiency can play a major role in the development of many diseases and disorders, including cancer, immune disorders, cardiovascular disease, diabetes and multiple sclerosis. In addition, recent research has shown that it has very strong epigenetic effects – although it cannot change our genetic information, it can influence which of our genes are expressed and which are not through chemical reactions.

History

Vitamin D got its name because it was discovered as the fourth vitamin in the order. It was isolated in 1932, its chemical structure was determined four years later, and it was not until 1959 that it was first produced synthetically.

Otherwise, it is one of the oldest molecules in the living nature, it was already formed by unicellular organisms living 750 million years ago. Because this vitamin is essential for building bone mass, its importance increased when living organisms began to leave the aquatic environment – staying on land increased the need for solid support for the body.

The manifestations of vitamin D deficiency, especially rickets or rickets, have been known for many centuries. The disease was first described in 1582.

Description

Vitamin D, or calciferol, comes in several forms. The most important are D2 (ergocalciferol), which is found in the plant kingdom, and D3 (cholecalciferol), which is of animal origin. Of particular importance to the human body is the form known as D3, which is much more readily available than vitamin D2 from plant sources (14).

Very important is the already mentioned epigenetic action of vitamin D. Chemically, it is a steroid hormone and can therefore bind to a specific steroid receptor directly on the cell nucleus, which is abbreviated as VDR (vitamin D-receptor). As a result, it can then influence a number of cell functions such as proliferation (rapid replication), differentiation (transformation from a non-specialized cell, such as a stem cell, to a specialized cell) or apoptosis (programmed cell death) (12).

Effects

Osteoporosis and the promotion of proper growth

Probably the most well-known function of vitamin D is its effect on bone building. It regulates the balance of calcium and phosphorus through a number of mechanisms. In the intestine, for example, it increases the production of a protein that ensures the absorption of calcium into the bloodstream; it also improves the absorption of phosphorus from the digestive tract and increases the resorption or reabsorption of calcium in the kidneys. Vitamin D also stimulates a system known as RANKL (receptor-activator of nuclear factor), which activates bone cells called osteoclasts that allow bone remodelling.

This makes vitamin D essential not only for the prevention of osteoporosis, but also for ensuring proper bone growth and development. Adequate intake is therefore essential in postmenopausal women, children, and pregnant women, as vitamin D levels in pregnancy have been shown to affect the growth of the child’s bones in early childhood (15).

Immunity and respiratory diseases

The effect of vitamin D on immunity and immunity is quite extensive. Firstly, it has an anti-inflammatory effect, which is important in defence against infections, and secondly, it has direct immunoregulatory effects, affecting both innate and adaptive immunity. In particular, it directly affects the activity of immune system cells – macrophages, T-cells, B-cells or dendritic cells. Interestingly, it can both enhance and inhibit their function, thereby preventing the onset and development of autoimmune diseases (see below) (16, 17, 33, 48).

Low vitamin D levels have been shown to be associated with susceptibility to infections, especially respiratory infections. This is also true for COVID-19 infection – low levels of “D” were observed in people who were hospitalized with this disease, which also increased the risk of death. Vitamin D also helps to reduce the cytokine storm, a violent inflammatory reaction that is one of the causes of the severe course of covid and other infections, and another typical complication of covid – blood clots. In addition, its use during the disease alleviates the subsequent damage to the lungs. (31, 32, 48-50)

Vitamin D levels in the body are also closely related to resistance to influenza. It’s no coincidence that flu epidemics come in the cold half of the year, when the body’s levels of “D” drop significantly – a link that has been repeatedly demonstrated by scientific research. This vitamin has a preventive effect against influenza, mainly by strengthening the innate immunity (one study, for example, showed a threefold decrease in the risk of infection when taking it), and thanks to its anti-inflammatory action, it also reduces the development of acute respiratory disease, thus significantly reducing the treatment time in the event of an infection.

Low levels of vitamin D may even play a role in tuberculosis, a bacterial lung disease that has not been eradicated even after the discovery of antibiotics because the causative agent has a high level of resistance to them. This link has long been known – in the days before antibiotics were discovered, cod liver oil was commonly used to treat tuberculosis and is one of the richest sources of ‘dee’. However, several recent studies have demonstrated the effectiveness of vitamin D supplementation with antibiotics (34-37).

Asthma and allergies

The results of research investigating the link between vitamin D and asthma also look very promising – again, vitamin D deficiency is one of the most important risk factors for the disease. “D” firstly reduces the production of inflammatory cytokines in certain types of T-lymphocytes and secondly reduces the activity of the FKN gene, which causes steroid resistance. The development of asthma may also be directly related to the VDR receptor, to which vitamin D binds in cells – in one study, for example, mice that had a non-functioning VDR receptor showed increased deposition of collagen in the airways and the development of hyperplasia (cell proliferation) in lung tissue (34, 38-40).

A susceptibility to asthma can arise during intrauterine development – research has shown that if a pregnant woman has enough vitamin D in her diet, the risk of her offspring developing asthma decreases significantly. The same is true for other types of allergies – for example, maternal vitamin D deficiency increases the risk of atopic eczema in the first two years of a child’s life and allergic rhinitis in the first five years. The use of “diac” can then directly reduce the severity of asthma in children (34, 41-44).

Chronic obstructive pulmonary disease

Another respiratory disease that may be related to vitamin D is chronic obstructive pulmonary disease (COPD), an inflammatory disease that leads to narrowing of the airways. Although it is a disease that develops in adulthood, its origins may be in childhood, and vitamin D may play a role in early lung development. In addition, in COPD patients, vitamin D signalling pathways are often disrupted, leading to dysregulation of inflammatory processes in the airways. However, its use may have a positive effect by regulating immune cell activity, improving airway smooth muscle strength and modulating the inflammatory response (34, 45-47).

Tumour diseases

Perhaps the most attention in recent times has been attracted by research into the role of vitamin D3 in the prevention and treatment of cancer. The basis of this role is primarily epigenetic.

Vitamin D3 regulates essential pathways of cell metabolism and differentiation through a steroid receptor in the cell nucleus known as VDR. As we said above, it can influence the processes of proliferation (rapid proliferation) and apoptosis (cell death), whose disturbances usually accompany cancer. It also influences other molecular mechanisms that play a key role in the cancer process – specifically, the activation of CYP27A1 and CYP27B1 and the inactivation of CYP24 enzymes).(1) Vitamin D3 also counteracts DNA methylation, a negative process that prevents certain genes from performing their function. Epigenetic mechanisms leading to DNA methylation are also a common feature of most cancers (7).

Several studies have shown that vitamin D3 can stop the cell cycle and affect the differentiation of cancer cells in different types of tumors (2-5). This is true for example in colon (5), breast (8), and prostate cancer (9). At the same time, people with certain types of cancer, particularly breast, prostate and ovarian cancer, have been shown to have reduced levels of vitamin D in their bodies. (18)

Cardiovascular disease

Vitamin D deficiency has been repeatedly found in virtually all persons studied who suffered a myocardial infarction.(22) Low levels of this vitamin have also been found in other cardiovascular diseases such as angina, heart failure and stroke.(20, 21)

Here too, epigenetic mechanisms such as DNA methylation or histone modification are most likely to blame.(23, 25, 26) Interestingly, epigenetic changes causing later increased susceptibility to cardiovascular disease are already present during intrauterine development, although only a link to inadequate maternal nutrition during pregnancy, especially low protein intake, has been demonstrated so far.(24, 27)

Vitamin D also plays an important role in protecting against cardiovascular disease by helping to regulate the renin-angiotensin system, a neurohumoral system that is involved in blood pressure regulation (48).

Multiple sclerosis

Research mapping the positive effect of vitamin D3 on people suffering from multiple sclerosis also looks promising, and here too its epigenetic action plays an important role. Although research on this topic has only been going on for the last ten years or so, it appears that epigenetic changes play a significant role in the disease – the processes of inflammation and demyelination (i.e. Moreover, the VDR receptor can regulate the activity of genes involved in multiple sclerosis.

For example, a 2014 study confirmed that increasing levels of vitamin D3 in the body reduce the activity of multiple sclerosis (10). A 2010 clinical study (6) showed that vitamin D3 has a stronger protective factor in female patients, which is due to the fact that the female sex hormone estrogen promotes the metabolism of this vitamin.

Inflammatory bowel disease

Other autoimmune diseases that have been shown to be related to vitamin D levels are those affecting the gut, particularly Crohn’s disease and ulcerative colitis. People who suffer from these diseases usually have significantly reduced levels, but it is not yet conclusively proven what is the cause and what is the effect – i.e. whether low levels of “D” cause inflammatory bowel diseases or whether these diseases lead to a deficiency of “D”. What is certain, however, is that vitamin D is essential for the maintenance of optimal barrier function in the gut, which is compromised in inflammatory bowel disease, promotes balance in the gut microbiome and has a strong anti-inflammatory effect. It is also true that patients with its deficiency are more likely to undergo hospitalization and surgical interventions. Therefore, supplementation with dextrose is clearly recommended for these diseases (54).

Lupus

Systemic lupus erythematosus is another autoimmune disease characterized by low vitamin D3 levels. It is a chronic inflammation that damages many organs and tissues in the body (including the brain) and can end in death. The added problem is that people with this disease often suffer from light-sensitive rashes, so they avoid being in the sun, which further exacerbates the “D deficiency” (and with it the course of the disease). Taking this vitamin is therefore a necessity here (55).

Rheumatoid arthritis

An inflammatory joint disease called rheumatoid arthritis is no exception among autoimmune diseases in relation to vitamin D. The deficiency of the “dee” is typical for it and its degree corresponds to the severity of its manifestations. Supplementation of this vitamin has the effect of reducing pain in the affected joints in particular, but also of reducing the risk of osteoporosis (64).

Diabetes

People with type I diabetes are known to have reduced levels of vitamin D in their bodies. In animal experiments, higher doses of this vitamin suppressed inflammatory processes in the pancreas and thus prevented the development of diabetes. Type II diabetes, a link has been found between vitamin D levels and the ability to metabolize glucose, and this vitamin also affects insulin secretion. (28) A large study (29) has also shown that people who have blood levels of vitamin D greater than 32 ng/ml are 41% less likely to develop type 2 diabetes than those with levels less than 19.5 ng/ml.

Testosterone, sexuality, fertility

Many cell types of the male reproductive organs, i.e. the testes, contain VDR receptors and enzymes involved in vitamin D metabolism. In addition, vitamin D appears to be directly involved in the regulation of testicular function. (62)

Therefore, for example, it is necessary for the production of testosterone, and if a man suffers from its deficiency, the level of this male sex hormone is reduced. This can result not only in reduced libido and erection problems, but also in weight gain, loss of muscle mass and physical performance, lack of energy and psychological problems. Meanwhile, long-term use of vitamin D3 research leads to increased testosterone levels. (56)

“D” also significantly affects fertility, both in men, where it affects the volume and quality of semen (VDR receptors are also found in the sperm itself), and in women. It is no coincidence that in the Nordic countries, where there is a significant lack of sunshine in winter, there are significant differences in fertility at different times of the year – most often couples conceive in summer and autumn, when vitamin D levels are highest. And even in our latitudes, a woman with higher levels of this vitamin has a higher chance of successful conception and a lower risk of miscarriage in the early stages of pregnancy. This, incidentally, is also true in the case of assisted reproduction (57-60, 62).

In addition, two of the most common gynaecological diseases that reduce the chances of pregnancy – endometriosis and polycystic ovary syndrome – are associated with vitamin D deficiency (61).

Weight Loss

Also, obese people have significantly reduced levels of vitamin D3 in their bodies compared to lean people, which may be due to the fact that this vitamin is stored in fat tissue, and although it can of course be released again, this process is very slow. Thus, when there is a lot of adipose tissue in the body, a large amount of “deficiency” is also stored in it, which is then missing in the body. Unfortunately, this condition also complicates the efforts to lose weight. One reason for this is that it is involved in the synthesis of adiponectin, a hormone that is produced in adipose tissue and is involved in the breakdown of fats and the regulation of glucose levels. Reduced adiponectin production is also typical of the so-called metabolic syndrome. Supplementation of the ‘dex’ can therefore promote weight loss in obese people. It can be particularly useful for postmenopausal women. (63)

Sources and method of use

The largest amount of vitamin D3, normally up to 90%, is produced in the skin when it interacts with UVB radiation. However, the ability to produce it decreases significantly with age, by up to 75%. The fact that the majority of the population spends less and less time in the sun and uses sunscreen when they do go out has a negative effect on its production. Currently, an estimated 30-35% of the world’s population is at risk of vitamin D deficiency (12); in the European population, the number of people suffering from vitamin D deficiency may be as high as 70% (30)!

However, Vitami D3 is also present in many foods of animal origin. The most important source is fish oil (cod liver is a particularly rich source), followed by egg yolk, liver and milk. It can also be taken in the form of dietary supplements, with vitamin D3 being more effective than the plant form of D2. (14)

As far as the recommended doses are concerned, they differ significantly from those previously stated. Currently, the minimum dose is 800 IU per day (12), but for therapeutic purposes, doses several times higher can be used.

Suitable combinations

Vitamin D is fat-soluble, so as a dietary supplement it should be consumed in combination with some fat. Fish oil (i.e. omega-3) is very suitable as it is a source of “D” in itself. Another common “partner” of vitamin D is calcium, as it is the “de” necessary for its absorption. Vitamin D3 also increases the biological activity of resveratrol, so this combination is also suitable.(76) There are many more possibilities, but here are some of them:

Osteoporosis: D3 + calcium (66), D3 + omega-3 (67), D3 + vitamin K2 (69), D3 + genistein + calcium (70), D3 + K2 + omega-3 + genistein (71)

Rheumatoid arthritis: D3 + calcium (65), D3 + omega-3 + curcumin (73), D3 + curcumin (74)

Cardiovascular disease: D3 + omega-3 (67), D3 + vitamin K2 (69), D3 + astaxanthin (75)

Female fertility: D3 + omega-3 (67), D3 + resveratrol (76)

Immunity: D3 + zinc + vitamin C (68), D3 + curcumin (72), D3 + astaxanthin (75)

Menopause: D3 + genistein + calcium (70), D3 + K2 + omega-3 + genistein (71)

Alzheimer’s: D3 + curcumin (72)

Inflammatory bowel disease: D3 + curcumin (74)

Testosterone: D3 + zinc

Diabetes: D3 + resveratrol (77)

Sports Performance:D3 + Quercetin