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Vitamin D: The Many Roles In Our Bodies

      

Abstract

Vitamin D is a fat soluble vitamin that contributes to overall health. Health professionals promote its importance due to its function in the human body. Several studies and research observe vitamin D's effects on health and its possible impact with certain diseases/illnesses; leukemia, hypertension, sickle cell anemia, and breast cancer to name a few. Findings include pro-founding information on vitamin D. There seems to be a coalition between vitamin D deficiency/toxicity and certain diseases/illnesses. Research has shown that vitamin D dosage does have an effect on health. However, there remains a gap in research and uncertainty on vitamin D's role in diseases and illnesses not related to bone health.

Keywords: Vitamin D, deficiency, disease, health, effects, research   

Introduction  

Essential vitamins are what our bodies need at most to function on a daily basis. They may or may not be as easily accessible as one would think; depending on the region we live in, along with the conditions and resources provided, as well as the physical state an individual might be in pertaining to health. Being one of the macronutrients that is globally considered to be a deficiency prone vitamin for some groups or individuals.  Mathebula (2015) states that the versatility of this vitamin in the human body along with functional roles goes down to the deepest level. In the long run it will be beneficial for those individuals who will be needing it more than those who would be considered at a healthy status. Individuals who are at a predisposition to chronic health related issues and more commonly diseases are more likely to not be well aware of some of the attributes that come with changing something as significant to their lifestyle. Vitamin D  not only utilized for optimal health in absorption, but also versatile in many of the major systemic functions, which includes but is not limited to; muscular, oncological, neurological and vascular functions, all working together to maintain a balance within one another even through critical or difficult conditions. They somehow manage to overcome circumstances that puts health related issues that are on the rise become more known but more so relevant and current topics of discussion.

The essentiality of vitamin D and how it plays a key role in maintenance of cell to cell association along with communication throughout entire systems of the body to keep levels at a stagnant state. When it comes to Physiological aspects of vitamin D and conditions related to various body systems, specifically blood and how toxicity levels can be altered, maintaining consistency in absorption levels is impertinent. In regards to muscular health, but more specifically skeletal muscle, the absorption of vitamin D is crucial for both the skeletal and muscular aspect, with consumption of this vitamin, status of previous or known complications can be monitored to measure levels of pain or previous health related issues. This not only applies to this systemic aspect, but is interrelated to all other systemic functions in some way shape or form.

According to research, the role of vitamin D in individuals with certain cancers is beneficial to the point where increasing intake or decreasing exposure can be helpful in the form of preventative measures.  How much vitamin D the body produces or absorbs and is distributed is based on many factors, demographically speaking where one lives and how they accommodate to that living arrangement is based on beliefs and what one does to improve lifestyle for improvement. Dietary intake, such as consumption of vitamin D rich foods or food sources that contain this essential macronutrient, is also a key player as to how people view or believe that vitamin D can affect them. According to Holman et al. (2017) affects on how one’s body, specifically skin, reacts to conditions such as skin cancer in the case of vitamin D absorption from sun exposure. In this case, being outside in conditions that individual put themselves in stresses out the body in which it has to acclimate under circumstances that are foreign or extreme and whether the certain limitations affect one's health in the certain situations as well as long term status.  

Without sufficient nutrient absorption needed to maintain performance of habitual and consistent tasks, insufficiency intervenes not only on a systemic but also physical and physiological level as well. According Gonzaga, & Gadini (2013) and the National Academy of Sciences, some individuals may be surpassing the safe limit of the daily vitamin D intake, which indicates toxicity levels over 2000 IU. This not only alters how one feels internally but externally some features or details are more prominent to intoxication or deficiencies in the case of someone not reaching the required needs or levels of vitamin D resulting in certain health related issues that affect prolonged overall health.

Improvement of conditions that affect one's health, as well as promotion in prevention of health related issues, are key players in awareness of the limitations that come with deficiencies that are related to vitamin D and conditions of  inadequate absorption for certain macronutrients. Several vitamin D health related issues and possible factors that affects its function in the human body will be discussed in this review. Vitamin D’s effect on bone health is a well known factor, however will not be discussed in this review.

Vitamin D a Versatile Function

Vitamin D is not just a vitamin that is essential for bone health, it also has significant roles in non-skeletal health, organ functions and prevention of disease. Vitamin D is a nutrient that is needed for optimal health. It is a group of fat-soluble secosteroids that is derived from cholesterol. Its main function is to aid in the absorption of phosphate, magnesium and calcium in the intestines.  The ways vitamin D is acquired is through diet, supplements and from sunlight exposure. Normally we obtain our vitamins from the foods we eat, but with vitamin D there is no food source high enough in this nutrient to solely sustain our bodies requirement. So, in addition to diet the major natural source is acquired through sunlight under the skin using a process called ultraviolet B sunlight exposure.

Vitamin D has two major chemically distinct forms which are D2 ergocalciferol (comes from plant sources) and D3 cholecalciferol (comes from animal sources). Vitamin D will be converted into a hormonal activity form calcitriol. The vitamin D prohormone compound plays an important role in the production of various physiological functions. It is so viable that most cells in the human body have a receptor for it. An adequate vitamin D status is important for optimal function of many organs. The action of vitamin D by the active metabolite 1,25-dihydroxyvitamin D [1,25(OH)2D] behaves as a hormone and binds to the vitamin D receptor (VDR) Stöcklin & Eggersdorfer (2013). All tissues and cells in the body, including immune, brain, colon, prostate and breast cells, among many others, have a vitamin D receptor (VDR) that coincides with 1,25(OH)2 D3. Since the VDR is widely expressed, 1,25(OH)2D3 has effects on many tissues.

It is now known that 1,25(OH)2D3 plays a role in the immune system and has effects on differentiation and proliferation of various cell types.  Vitamin D is also known to regulate the immunity by increased production of antimicrobial peptides and subsequent killing of bacteria. The innate immune system serves as the first barrier of defense against invading microorganisms.  It is to identify foreign organisms and stimulate a cascade of events that result in the removal or destruction of the invading organism. Pattern recognition receptors are expressed by cell of the innate immune system to identify molecular patterns that are reserved amongst different classes of pathogens. These patterns are known as pathogen associated molecular patterns (PAMPs). Different forms of PAMPs are lipopolysaccharides (LPS), viral proteins and single/double stranded RNA. The innate immune system response depends on the specific toll like receptors (TLRs) or the TLRs that stimulate PAMPs. TLRs include TLR2 which responds to gram-positive bacteria and mycobacteria, TLR4 which responds to gram-negative bacteria and TLR3 which responds to double-stranded RNA associated with viral infections. The response to TLR signaling produces the production of anti-microbial peptides, cytokines and apoptosis of the host cells among responses (Stöcklin & Eggersdorfer, 2013).

The major form of anti-microbial peptides in humans is cathelicidin. Cathelicidin serve as a critical role in innate immune defense against bacterial infection. Cells of the immune system including neutrophils and macrophages and cells lining epithelial surfaces that are constantly exposed to potential pathogens (skin, respiratory tract and gastrointestinal tract) produce cathelicidin. Cathelicidin plays an integral part of the innate immune response due to its anti-microbial activity against gram positive and negative bacteria as well as certain viruses and fungi. Vitamin D activates macrophages and induces them to increase their production of the antimicrobial peptide cathelicidin. This breaks down pathogens once the macrophage has consumed them. It also creates a recursive effect whereby vitamin D both generates more innate immune cells and makes them more effective at destroying harmful organisms.  The effect of vitamin D is in connection with the stimulation of these antimicrobial proteins and UVB radiation, which induces the production of the vitamin.

The association between vitamin D deficiency and autoimmune disease is the anti-inflammatory and immunomodulatory functions, as well as the presence of VDRs on most immune cells. The most established link between environmental factors and autoimmunity is within the interactions between infections and autoimmunity. Vitamin D deficiency is common in patients with autoimmune diseases. As seen in patients with Multiple sclerosis (MS), type 1 diabetes, irritable bowel disease and rheumatoid arthritis, vitamin D seems to affect the activity and outcomes of the autoimmune diseases. MS is an autoimmune demyelinating disease in which the insulating covers of the nerve cells in the brain and spinal cord are damaged. MS is most common in women, that are in certain ethnic populations and living in high altitudes with low sun exposure. Several genetic and environmental facts have been implicated in its development. It appears that low levels of vitamin D are common in patients with MS and has been identified with the increase relapse of MS (Levin, Theodor, Segal, et al., 2013). Vitamin D was reported to induce changes in the gene expression of immune cells within patients with MS. The autonomic dysfunctions combined with inflammation is a critical factor in the development of MS. The autonomic dysfunctions were found to be altered by environmental factors such as the Epstein-Barr virus and vitamin D and possible the combined effect of both (Sternberg, 2012).

Several tests were performed on patients with MS and doses of vitamin D. The first test identified low doses for 6 months and there were no significant or radiological effects. Another test was performed with the increase dose for over a 28-week period followed by and additions 10,000 IU/day for 12 weeks. According to Levin et al. (2013), This dose appeared to be safe and the relapse rate showed an apparent decline. Supplementation was suggested to be beneficial for the primary prevention of autoimmune diseases as MS and diabetes mellitus.   

In the past, the major source if Vitamin D was exposure of sunlight. One possible cause of vitamin D deficiency is the lack of unprotected sun exposure. Current barriers to sunlight are the fear about attaining melanoma and other types of skin cancer which warrants the avoidance of midday sun exposure. This has led to an increase in sunscreen, hats and other sun barriers. Environmental factors such as pollution and fewer hours in the winter months decrease exposure and ultimately contributes to the loss of vitamin D synthesis from sunlight exposure. The sun exposure helps satisfy the body requirements.  For people who live at 33° Latitude these observations in particularly strengthen the argument for supplementation (Grant, et al., 2009).  Another possible cause is lack of dietary source of vitamin D. It is difficult for adults and children to obtain high levels of vitamin through a dietary source without supplementation. Currently there has not been a specific amount established for a regimen of vitamin D therapy for immunological homeostasis. Numerous epidemiological studies have suggested that a 25(OH)d blood level above 30 ng/ml may have additional benefits in reducing the risk of common cancers, autoimmune disease, cardiovascular disease and infectious diseases. (Holick, et al., 2011)

Vitamin D and Diabetes

According to The International Diabetes Federation, diabetes affects 425 million adults worldwide, with the total set to reach 629 million by 2045. In the United states, an estimated 79 million people have prediabetes. There is growing evidence that deficiency of vitamin D is a large contributing factor in the development of both type 1 and 2 diabetes. Vitamin D improves glucose tolerance and improved insulin secretion. The b-cells in the pancreas that secretes insulin express the VDR and respond to 1,25(OH)2D by increasing insulin production. It does not participate in generating the new β-cells. Therefore, 1,25(OH)2D3 seems to have a role in the prevention of diabetes in early age and/or improving of diabetes rather than treating the disease. The indirect effects of vitamin D may be mediated via its important well-recognized role in regulating extracellular calcium and calcium flux through betta cells. Insulin secretion is a dependent upon calcium process. Alterations in calcium flux can have effects on b-cell secretory function  through the cell membranes. Therefore low vitamin D may affect calcium’s ability to affect insulin secretion (Martin & Campbell, 2011).

There is research that speculates the relation between vitamin D and gestational diabetes mellitus (GDM). Like other changes that occur during pregnancy, GDM is a common condition in which many women are diagnosed with. There is little evidence that links genetics to the occurrence of GDM of some women. Therefore, diet is the main factor that affects women’s risk of developing GDM; before and during pregnancy. However, there are patterns that speculate risk factors for women before and during pregnancy. Women are often encouraged by health care professionals to maintain their health during childbearing years. GDM occurs during pregnancy in which women develop insulin resistance correlated with carbohydrate consumption intolerance (Alzaim & Wood, 2013). Individuals diagnosed with GDM have a fasting plasma glucose level that reads 126mg/dl and an initial plasma glucose level that reads 200 mg/dl. Women with GDM also are shown to be vitamin D deficient, thus raises the possibility of a relationship between the two. This is furthered explained when considering the role vitamin D plays during pregnancies.

The placenta, in which the fetus receives nutrients, contains vitamin D receptors and activating enzyme 1-α-hydroxylase (Maysa et al., 2013). Despite this knowledge, there is not enough scientific evidence to prove that vitamin D affects pregnancy. Therefore, the question still remains as to why vitamin D is a major nutrient requirement for the fetus, as well as why many pregnant women have low vitamin D levels and are diagnosed with GDM. It is also argued that the fetus requires certain vitamin D dosage throughout development. This dosage requirement peaks during the third trimester, thus increases the fetus’ needs of the vitamin. Confusion over the importance of vitamin D during pregnancy has also affected people’s knowledge of the benefits of taking vitamin D supplements while pregnant (Mitchell & Sanders, 2018).  

Early prevention and becoming informed as to what certain diagnosis for these life altering conditions such as diabetes mellitus or gestational diabetes mellitus; as well as making changes to previous habits, significantly can bring on a better outcome. Taking preventative measures to ensure one doesn’t acquire this diseases as well as other diseases alike early on, but also maintaining a consistent routine that brings awareness, are indicators that health status should be a more concerning  topic of discussion.

Blood Health and Vitamin D

Vitamin D plays major physiological roles in the body as a steroidal hormone. It is critical to note that the Deficiency or in excess the imbalances result in blood-related problems. When In excessive amounts within the human body, Vitamin D results in a rare but potentially serious condition called Hypervitaminosis D. This condition is popularly known as the “Vitamin D toxicity”. This type of Vitamin D toxicity is caused by large amounts of Vitamin D in the body which results from mega-doses of Vitamin D supplements. It is critical to note that Vitamin D toxicity is not caused by the conventional ways of obtaining the nutrient through diets and sun exposure. This is because the body has mechanisms in place that regulate the amount of vitamin D produced and obtained through the sun exposure or continuous intake of fortified foods and diets. These two sources do not contain copious amounts of the mineral and hence cannot results in Vitamin D toxicity. Vitamin D toxicity is characterized by consequences such as an excessive buildup of calcium in the circulatory system affecting the blood . This is a condition referred to as Hypercalcemia. Hypercalcemia is characterized by symptoms such as nausea, vomiting, weaknesses and frequent urination. Healthy blood contains the right amount of calcium hence a deviation affects functionality and can result in disorders that are systemic such as formation of calcium stones.

The normal human has a blood pressure of between 120/80 mmHg and 140/90 mmHg. A deficiency in Vitamin D disrupts this normalcy to levels that are considered high blood pressure. Vitamin D deficiencies in Healthy people have been linked with the development of stiffer arteries and the inability of some blood vessels to relax. This results in deteriorating vascular health. A problem in the vascular system affects what is referred to as healthy blood or circulatory system. According to these assertions, it is reasonable to infer that lack or efficiencies of vitamin D impair the individuals vascular health which contributes to high blood pressure as well as risks of cardiovascular disorder. Higher blood pressure is linked to several blood complications such as the formation of blood clots. Blood clots, or as commonly referred to as a thrombus, obstructs the flow of blood to other areas and is defined as the final product of coagulation step in hemostasis. The process of hemostasis in uninjured vessels is a critical health concern considering it obstructs blood flow and can result in lower levels of blood flow into the brain.
Another growing blood health issue is leukemia. Leukemia is known as that the cancer of the body’s red blood cells. Leukemia has in the recent past been linked to Vitamin D deficiency. This is mainly associated with people who are exposed to minimal or no sunlight at all. A number of studies has shown that vitamin D metabolites have something to do with the growing cases of Leukemia in people living far from the equator. This is because Vitamin D has a metabolite in blood known as the 25-hydroxyvitamin D, or 25(OH)D. This is the indicator used to measure the levels of Vitamin D levels in a human body. These metabolites interact with the Acute Myeloid Leukemia cells (AML). To add to this argument majority of the studies involving people with Leukemia have noted a lower level of Vitamin D. Skin photosynthesis accounts for a large proportion of 25(OH)D concentration. As a result, the inverse association between cloud-adjusted solar UVB exposure and incidence rates is likely to be mediated by circulating 25(OH)D, which is highly dependent on solar UVB irradiance. In simpler terms, this study suggests that an increased level of UVB irradiance and Vitamin D are critical in ensuring that people away from the tropics and the equator who receive minimal sunlight can prevent the development of Leukemia.
It is critical to note that Vitamin D has been known for its role in Calcium regulation. However, the implications in hematological cancer pathogenesis have provided a major challenge and an insight into anti-cancer therapy. Serum levels of 25(OH)D3, the precursor to the active form of vitamin D, calcitriol, are frequently lower in patients with the hematological disease compared to healthy individuals. This correlates with the worst of the disease outcomes. In the same context, the diseased cells also exhibit a higher level of Vitamin D reception which causes abnormalities in blood cells. However, not all side effects of the lack or presence of vitamin D are bad. This is because supplementation of Vitamin D improves apoptosis which is a systematic and body induced cell death especially damaged or worn out cells, induces differentiation of cells in the body, prohibits proliferations and most importantly Vitamin D in blood health helps to sensitize the tumor cells in conjunction with other cancer therapies. It is however notable that the control of Vitamin D levels is critical because the amounts that are required to achieve these functions listed successfully can induce hypercalcemia in humans.
It is critical to note that blood health is dependent on the health of individual cells. For example, a small deviation from the normal blood cells is considered abnormal. A good example is a change in the shapes of red blood cells in sickle cell anemia patients. This is a genetic disease that is characterized by abnormal hemoglobin which is the primary constituent of the red blood cells. It is notable that people with Sickle cell disease have severe nutritional deficiencies. One of these deficiencies is Vitamin D. The symptoms of Vitamin D deficiency in sickle cell patients include chronic pain. This means that the levels of Vitamin D in the system affect the severity of sickle cell anemia resulting in more complications. Considering the basic fact that Vitamin D deficiency and sickle cell anemia share the same clinical manifestations for bone health, chronic inflammation, and pain, it is reasonable to infer that the Vitamin D deficiency contributes to the growth of the sickle cell anemia condition. In simpler terms, by optimizing Vitamin D nutrition, we achieve an inexpensive strategy to improve blood health as far as sickle cell disease is concerned.

Lastly, it is important to consider the effects of Vitamin D deficiency on the basic functionality of blood clotting. As explained before Vitamin D is associated with the regulation of calcium levels in the system. Calcium ions are critical for the entire process of clotting. Calcium ions are basic elements for clotting to occur. Lower levels of Vitamin D means that there will be lower levels of calcium which results in hemophilia commonly referred to as the bleeder disease. This affects the entirety of blood health in several aspects; entry of microorganisms considering that clotting blocks entry of pathogens and the loss of blood which is also a critical element of blood health and general blood health. This is because the basic elements of the human immune system are anchored in the blood which holds the white blood cells.

Vitamin D and Skeletal Muscle Tissue

Vitamin D has been established for some time as an important factor for bone mineralization however, when it comes to the skeletal muscle tissue, new research on vitamin D’s positive functions and effects are still being uncovered. The method researchers are using to uncover the process of communication between skeletal muscle and vitamin D is VDR (Vitamin D Receptor). The VDR is a transcription factor that is activated by 1,25-dihydroxyvitamin D that regulates gene transcription in the body. Depending on the amount of 25(OH) D in the tissue they can focus in on that specific location to examine VDR’s process. VDR however, is difficult to find which is why this method of confirming a deficiency of vitamin D in skeletal tissue remains in its experimental phase. Limited research have been published that examines an association between muscle pain and vitamin D stores in humans, in addition to lab mice.

In one study, they conducted an uncontrolled study that examined 150 patients with chronic, musculoskeletal pain that uncovered 96% of the patients had vitamin D deficiency, with a mean of 25(OH) D of 10.49 ng/ml. (S. Bobo Tanner and Susan A. Harwell, 2015). This allowed the researchers to gather data on patients that were at higher risk of hypovitaminosis D meanwhile, extending the risk for deficiencies of vitamin D in other populations as well. In another randomized trial that contained a sample size of 30 women with fibromyalgia, that ensues widespread muscle pain and tenderness, also measured 25(OH) D levels. Depending on the womens vitamin D baseline levels they were either given 1 of 2 doses of 1200-2400 IU cholecalciferol (Vitamin D3) a day. This study however did uncover a decrease in pain in relation to vitamin D status compared to the control group. The researchers concluded that the patients in the experimental group has less muscle pain overall. The researchers however, did comment on the limitation of their 30 person sample size and how  improving health-related quality of life and disease impairment scores were not statistically significant for reducing overall pain with the supplementation of vitamin D (Wepner, et al. 2014).

Myopathy and sarcopenia also remain as a focal point for certain studies that associate vitamin D and the benefits the vitamin can do for the tissue. These ailments pertain to muscle weakness and low muscle mass in the skeletal tissue. As a population continues to grow old and or living farther from the equator, bone mass decreases in density and strength due to reduced sun exposure and non fortified vitamin D foods. Researchers are exploring vitamin D’s benefits and effects on the muscle tissue by uncovering the physiology of vitamin D receptors (VDR) in the skeletal muscle and how vitamin D is being used by these receptors. This however remains as an area for opportunity for researchers because certain studies question that VDR even exists in the muscle tissue.

A very thorough continuous three part study decided to look into the presence of VDR in human myoblasts in addition to the relationship of vitamin D. The initial study harvested and cloned human myoblasts from healthy volunteers that were supplemented with 1 of 3 doses of 1,25-dihydroxyvitamin D. The researchers used polymerase chain reaction (PCR) to measure VDR in the myoblasts before and after supplementation. They discovered that they were able to measure VDR with PCR in the myoblasts. The second part of the study was a randomized controlled intervention study. It also had positive results by doing a similar vastus lateralis muscle biopsy on 20 women over the age of 65 with a semi deficient baseline of 25(OH)D levels and mobility restraints. They examined the supplementation of 4000 IU’s of vitamin D3 and a placebo for skeletal muscle morphology and VDR protein concentration. They were able to detect much more active VDR in the experimental group by conducting PCR, immunoblotting and immunofluorescent markers. The third final study, had a sample size of twenty mobile limited adults. They found that at fasting baseline levels of 25(OH)D and muscle biopsies, VDR protein expression by immunoblotting consisted of positive results of VDR detection in the skeletal muscle. The researchers did not find a correlation between VDR mRNA expression nonetheless, there was a larger VDR concentration in those with adequate amounts of 25(OH)D compared to those with deficient levels. S. Bobo Tanner and Susan A. Harwell. (2015).

Vitamin D is used in a variety of molecular pathways in the human body that can benefit skeletal muscle, bone formation and hormonal communication. The role of vitamin D is also suggested to mediate calcium and phosphate functions in the muscle regarding plasticity, contraction, mitochondrial function and insulin signaling. The researchers of this study tested supplementation of 20,000 IU cholecalciferol (vitamin D3) alternating days for 10-12 weeks in vitamin D deficiency individuals. It resulted in greater mitochondrial oxidative function as it pertained to phosphorus-31 magnetic resonance spectroscopy (P-MRS). The P-MRS is a noninvasive method that is used to assess mitochondrial processes by measuring the kinetics of high energy phosphate metabolites involved in ATP metabolism during and after exercise (Sinha, A., et al. 2013).

Vitamin D’s role in the skeletal tissue can take a variety of pathways that can associate it attributing to muscle weakness or myopathy. The functions in the body with the dosages that were used in the presented research clearly varies across the board from 4000 IU to 20,000 IU  however the data may prove to be useful in future studies that pertain to myopathy and other illnesses relating to skeletal muscle. It would be safe to say to adequately consume vitamin D foods daily and if possible be in the sun for periods in a day. Another recommendation would be to do some form of physical activity because it would synergistically benefit skeletal muscle strength, bone mineral density, and overall wellness.

Vitamin D and Cancer

Vitamin D is an interesting and unique vitamin because it is considered a nutrient and a prohormone and is strongly known for its effects on building and maintaining strong bones. However, recent studies have observed a link between low vitamin D levels and an increase in cancer risk and progression. Specifically, research suggests that women with low levels of vitamin D have a higher risk of breast cancer and men and women with low levels of vitamin D have a higher risk of developing colorectal cancer. Vitamin D plays an important role in stimulating immature cells to become mature functioning cells. It transfers into the nucleus of a cell and up regulates selected genes coding for specific proteins involved in cell differentiation. Some evidence suggests that the function of vitamin D may help prevent certain types of cancers. Although this connection warrants further investigation, Vitamin D's role in cell differentiation may highly be involved.

Breast cancer is one of the most commonly diagnosed cancers among women. O’Brien et al. (2017) demonstrates how effective serum vitamin D levels and supplemental intake of vitamin D has on women who are at risk of developing breast cancer and women who were diagnosed with breast cancer. 50,884 U.S. women ages 35 to 74 were enrolled in a sister study from having a sibling who has had breast cancer, but has never developed breast cancer themselves. Of the 50,884 women, 1,611 women who later developed breast cancer and 1,843 randomly selected cohort participants were selected to be in a five year study. Each participant filled out a questionnaire about their race, if they were on birth control/ hormonal supplements, menopausal status, alcohol consumption levels, physical activity, BMI, and family history. They also evaluated the relationship between breast cancer and vitamin D sources, including supplements, diet, and sunlight exposure.
The root of the study is the concentration of vitamin D found within blood. Researchers referred to it as serum 25(OH)D, which is the main indicator of vitamin D in blood. All participants were given vitamin d supplementation and were contacted each year to make certain of any major health changes.
Overall, women with low levels of Vitamin D are at higher risk for developing breast cancer. As a result 38.0 ng/mL of calcifediol was connected with a lower risk in breast cancer by twenty one percent compared with levels less than 24.6 ng/mL. The association with lower risk of breast cancer was most strongly evident for  postmenopausal and obese women. It was also noticed that a lower risk of cancerous cells associated with regular vitamin D supplement consumed more than four times a week was more beneficial than average users. In fact, these results are quite consistent with those of the Recommended Daily Allowance of 400 IU/day. The results support the theory that supplements of Vitamin D could be effectual in preventing breast cancer by controlling normal breast cell growth and stopping breast cancer cells from progressing.
In another study, Hamada et al. (2018) observed if high levels of vitamin D is linked with a decrease in colorectal cancer. Colon cancer is also a highly common cancer and is the top leading cause of cancer-related deaths in the United States. In this study, 869 participants with colon cancer were evaluated of an association of post diagnosis Vitamin D scores which came from diet and lifestyle factors in order to guess plasma 25(OH)D levels. They hypothesized that the survival colon cancer rate and connection with Vitamin D with is possibly stronger for tumors with lower lymphocytic response than  tumors with a higher lymphocytic response.
Each patient was followed up upon until death or end of the study. Post diagnosis predicted calcifediol score fairly correlated with pre diagnosis predicted calcifediol score. During the median follow-up time there were 480 all-cause deaths. Of the 480 deaths, 122 of them were from colorectal cancer. As a result, they did not observe a statistically significant interaction between post diagnosis predicted vitamin D score and lymphocytic reaction in relation to overall mortality.
Assuming that predicted vitamin D levels can possibly have an effect on any other factors used in the prediction model, they included the patients physical activity level as a further outcome. They concluded that the beneficial survival connection of post diagnosis predicted Vitamin D  worked better for patients with colon cancer who have lower peritumoral lymphocytic reaction. However, they did not observe a difference in overall mortality rate. To determine if their theory is valid, they performed this study on two large prospective cohort studies. The predicted vitamin D score came from dietary and lifestyle data, which included both endogenous and exogenous sources of vitamin D and estimates of long-term plasma levels.
The association of Vitamin D levels with the mortality of colon cancer varied by levels of peritumoral lymphocytic reaction. The multiple adjusted transience ratios for five equal groups increase of Vitamin D levels were 0.69 and had ninety five percent confidence interval. Other findings with lower peritumoral lymphocytic reaction were 1.08 and ninety five percent confidence interval. The survival association of the 25(OH)D score was not notably different by Crohn’s-like lymphoid reaction, tumor-infiltrating lymphocytes.
In conclusion, the connection between Vitamin D levels and success rates of colon cancer is stronger for carcinomas with lower peritumoral lymphocytic reaction. Their results suggested a correlation of vitamin D and immune response may contribute to their own diet and  lifestyle. This newest study does not show that there is a benefit to supplementation, however it does show a positive association with higher levels.

Lastly, studies show Vitamin D may protect someone against the development of skin cancer. Vitamin D which is also known as the sunshine vitamin can be made in large amounts when exposed to the sun. The sun's UVB rays hit cholesterol in the skin cells, providing the energy for vitamin D synthesis to occur. Once Vitamin D is activated it influences the genes in your skin and helps prevent the type of abnormalities that ultraviolet light causes. As a result, sun avoidance becomes the factor that ironically activates skin cancer.

        Park et al. (2016) evaluated 63,760 women and 41,530 men from for 26 years to determine if dietary and supplemental intake of Vitamin D correlated with skin cancer. They acquired information by doing food frequency questionnaires, dosages of multivitamins every four years, and physical activity levels. Once dietary Vitamin D nutrients were calculate, they conducted stratified analysis according to major sun exposure variables, such as history of sunburns and the average amount of time in the sun since high school.

        In conclusion, higher levels of vitamin D intake was positively associated with risk of Basal Cell Carcinoma while a non-significant increased risk was found with melanoma. Participants with higher intake of total vitamin D tended to be older, participate in regular physical activity, and used more sunscreen. Both men and women with lower total vitamin D intake were more likely to smoke, and consumed higher amount of alcohol intake. Evidence suggests it would be best to get a reasonable amount of unprotected sun exposure on a large amount of bare skin just before your skin starts turning pink, and then cover up with a thin layer of clothing.
Like any other cancer, breast, colorectal, and skin cancer is caused by multiple issues such as diet, exercise, lifestyle choice, and genetics. Vitamin D is just one part of that solution to possibly help prevent it. The safest things to do to avoid these types of cancer would be to ensure that there is adequate vitamin D in the diet. Until better evidence emerges, continuing to take a cautious approach to vitamin D supplementation seems the most reasonable approach. Although findings are solely observational, there is no conclusions about the link between vitamin D and cancer risk. There is an optimal level of vitamin D that protects against cancer, but an overconsumption of this level offers no further benefit.

Conclusion

Being that vitamin D is an essential vitamin, it is not surprising to know that deficiencies and overdosage will have a major impact on health. As discussed, vitamin D can be obtained from the diet, sunlight, and supplementation. More than just a vitamin that supports bone health, vitamin D has other benefits which is associated with different conditions and functions in the body. For example, a contributing factor to vitamin D’s importance is its impact on regulating the immune system. Individuals with deficiencies of vitamin D can be linked to the development of autoimmune diseases. Autoimmune diseases involve healthy living cells being killed off by the immune system; instead of the immune system strengthening the body’s defenses in fighting bacteria and illnesses.

It is argued that when proper dosages are not reached individuals can develop illness and diseases such as hypercalcemia, leukemia, breast cancer, diabetes, and sickle cell anemia. Although vitamin D deficiency is a major issue in our health, toxicity of this vitamin is also a cause for concern; toxicity in this form is referring to the excess amount of vitamin D in the body. As mentioned earlier, hypercalcemia is the result of calcium buildup in the blood resulting in vitamin D toxicity, and ultimately affecting our circulatory system. In addition to this, the structure and function to blood vessels relies on the intake of vitamin D leading to cardiovascular disease or related disorders. High blood pressure is the result of abnormal functions of blood vessels and can further lead to the formation of blood clots, thus inevitably increase chances of a stroke. While there are other factors that affect stroke risks, it cannot be ignored that vitamin D may also play a role in its formation. In this case, prevention measures must be taken place.

Because Vitamin D is known as the “sunshine vitamin” it would be appropriate to contemplate the implications and diseases that occurs with the lack of sunlight. Previously mentioned, leukemia is blood cancer that can be linked to lack of sunlight. Therefore, in certain regions of the world where there is limited sunlight, it would be expected that individuals who reside in these regions are prone to develop leukemia; proper UVB exposure can prevent leukemia for these individuals.

However, as beneficial sunlight can be, it is also important to take proper precautions when out in the sun because too much sunlight can also cause negative effects. It is important to consume water to prevent dehydration and even apply sunscreen when exposed to the sun for a long period of time (Bentley, 2013). It should be noted that this is only in the case of potentially too much sun exposure, thus normal exposure will not warrant these measures and in fact decrease sun exposure when it is needed. It was further discussed that other cancers such as breast cancer maybe linked to low doses of vitamin D. Inadequate vitamin D can further affect already existing diseases, such as individuals with sickle cell anemia who state that under these conditions they suffer from chronic pain. By contrast, adequate amounts of vitamin D would improve the condition of patients who suffer from sickle cell anemia.

The importance on vitamin D for bones has always been highly discussed and encouraged by health professionals. However as indicated above, currently it is speculated that vitamin D also impacts skeletal muscle. Although several studies and research were conducted testing this knowledge, and some that concluded with some convincing results, there is little profound evidence or explanation to make this discovery undoubtedly true. This can be an area for further research in which researchers discover how skeletal muscle and vitamin D are related; more information on the vitamin D receptor.  This discovery would be a breakthrough in research because it would explain certain individuals who suffer from muscular pain and weakness. Also, it would give individuals more incentive to include vitamin D in their diet and from other sources.

There is even more room for further research. Unfortunately, there is little evidence that supports vitamin D’s role in preventing cancer, thus should not be used as a preventive measure (Bentley, 2013). Therefore, researchers and scientists need to find further information that supports their theories on cancers and disease such as HIV and cardiovascular disease. Furthermore, additional research can include vitamin D deficiency in different age groups and how it affects development in children as well as mental and physical capabilities in adults. There is definitely a gap in research as far as vitamin D’s role in pregnancy and its effects on GDM. Health professionals need to develop a strategy to effectively promote vitamin D for pregnant women when research shows that it has no substantial effect on pregnancy. Lastly, the costs of research as far as prevention and other measures should be discussed (Aguiar et al., 2017). It should be indicated if such prevention will be beneficial in the long run and its impact on the economy and health care facilities.

It is imperative to know the implications that arise from lack of or excessive vitamin D. For instance, it is suggested that by knowing the results of improper vitamin D dosage it can then be prevented and studied further. One obvious measure to prevent vitamin D deficiency is through implementation in the diet. Diets should include tuna and salmon, dairy products that have been fortified with vitamin D, and egg yolks. Ultimately, there is not enough evidence that proves vitamin D as a prevention to many cancers, diseases, and illnesses. However, it is found that a person’s overall health will improve with adequate vitamin D.  Although vitamin D is just one of the factors that affect the diseases and illnesses discussed earlier, it is still worth observing and realizing its impact on overall health. It is especially important in underdeveloped countries where there is high occurrence of vitamin D deficiency. Health professionals in these countries can take this research to encourage implementation of vitamin D in patients’ diet, as well as promote it in the community. Undoubtedly if there is more knowledge and resources, deficiency in these countries and around the world will greatly reduce.

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