Sunlight, skin, vitamin D, breast cancer, they are closely related! Vitamin D deficiency in the human body is associated with the development of breast cancer, and vitamin D can also treat breast cancer and improve the outcome and prognosis of patients… Let’s take a look at the relationship between them. Vitamin D Overview First of all, let’s learn about vitamin D. In 1921, Elmer McCollum, an American scientist, discovered a fat-soluble vitamin that could prevent rickets, and was named “vitamin D” as the fourth discovered vitamin. It is now believed that vitamin D is also a steroid hormone, and there are five compounds in the vitamin D family, the most important and closely related to health being VD2 (ergocalciferol) and VD3 (cholecalciferol). Plants do not contain vitamin D, but vitamin D prodigiosity is present in both animals and plants. Vitamin D are all derivatives of different vitamin D prodrugs after UV irradiation. They have the following three properties: it is present in some natural foods; the human body has subcutaneous stores of 7-dehydrocholesterol produced from cholesterol, which is converted to vitamin D3 when exposed to ultraviolet light. the two main sources of vitamin D for humans are diet and sunlight exposure. Some natural foods contain large amounts of vitamin D, such as fat-rich fish, eggs and dried mushrooms, but 90-95% of vitamin D is synthesized from sunlight exposure to the skin (UV-B radiation), and is therefore known as the “sunshine vitamin”. It is well known that doctors recommend calcium and vitamin D supplements for the elderly with osteoporosis, children and adolescents in the process of growth and development, and pregnant women, precisely because vitamin D can maintain normal calcium and phosphorus metabolism in the body and protect the body’s bone health. More and more studies have found that vitamin D deficiency in the body may be closely related to the occurrence and development of many kinds of tumors, which include breast cancer, rectal cancer, pancreatic cancer, lung cancer, etc. Vitamin D modulates some of the characteristics of cancer and has certain anti-cancer effects. For example, these include inhibition of cancer cell proliferation, invasion, metastasis and angiogenesis, and induction of apoptosis and differentiation of cancer cells. In addition, vitamin D regulates the innate and acquired immune functions of cells. Our research team has used breast cancer cell lines and breast tumor patient specimens to study the relationship between vitamin D and receptors and breast cancer using different technical methods, and found that vitamin D and receptors are closely related to the formation, progression and associated calcification of breast cancer, and are involved in inhibiting the process of breast cancer, and clinical application of vitamin D for breast cancer has achieved certain efficacy and experience. Vitamin D deficiency, current status of deficiency and its supplementation In the United States, about more than 35% of healthy young people have vitamin D deficiency. More than half of Hispanic and African American adults in Boston are vitamin D deficient, and 48% of young white women in Burma are deficient. This rate is even higher in Middle Eastern and Asian countries. About 40% of African American women aged 15-49 years have 25-hydroxyvitamin D levels below 15 ng/ml. 69% and 24% of the middle-aged and elderly population in China are vitamin D deficient and inadequate, respectively. The proportion of vitamin D deficiency among women with breast cancer is essentially similar, and the risk of vitamin D deficiency is higher among non-Caucasians or those with a BMI >25 Kg/ m 2. Most physicians believe that serum 25-hydroxyvitamin D levels above 30 ng/ml are necessary for optimal bone health to adequately facilitate intestinal calcium absorption and prevent secondary hyperparathyroidism and its effects on the skeletal system. Vitamin D levels above 20ng/ml but less than 30ng/ml are considered to be deficient. There are many causes of vitamin D deficiency, including inadequate sunlight exposure, winter, high latitudes, inadequate vitamin D intake, and certain pathophysiological conditions such as pregnancy, exclusive breastfeeding of infants, dark skin tones, obesity, malabsorption syndrome, and liver and kidney failure. As mentioned earlier, vitamin D is mainly produced by sunlight exposure in the skin, and there are many factors that can affect the process of vitamin D synthesis in the skin. The use of sunscreens with a sun protection factor of 30 can reduce skin synthesis of vitamin D by up to 95-99%. Compared to whites, melanin in the skin of people of color, like natural sunscreens, can reduce the production of vitamin D in the skin by up to 90 percent. In addition, air pollution such as increased absorption of UVB radiation from ozone and nitrogen dioxide in the atmosphere is also considered to be one of the factors that can easily be overlooked as a cause of vitamin D deficiency. Because most foods contain little to no vitamin D, the amount of vitamin D in the body is largely determined by sunlight exposure. Sun exposure is the easiest and most economical way to obtain vitamin D. Adequate daily outdoor activity and exposure to sunlight can help the skin synthesize vitamin D to meet most of the body’s needs, but for people with limited living conditions, seasonal changes, dark skin tones, and certain specific groups of people (e.g., those with limited outdoor activity, the elderly, liver and kidney failure, and increased physiological needs during pregnancy), their own ability to synthesize vitamin D must be reduced. For people with reduced ability to synthesize vitamin D, they must rely on dietary supplements or vitamin D preparations to meet their vitamin D needs. The dose of vitamin D supplementation varies in different situations and at different ages. The Institute of Medicine and the Endocrine Practice Guidelines Committee recommend different doses of vitamin D supplementation for the general population and for people at high risk of vitamin D deficiency. Because vitamin D is a fat-soluble vitamin, animal foods are the main source of natural vitamin D, such as cod liver oil, marine fish, fish eggs, animal liver, egg yolks, and cheese. However, there are not many foods rich in vitamin D. Therefore, it is also feasible and necessary to use vitamin D fortified foods or vitamin D supplements when natural vitamin D is not obtained sufficiently. Vitamin D and Breast Cancer In one of the first U.S. National Health and Nutrition Examination studies, 5009 white women had their vitamin D exposure assessed by personal interview and dermatological examination. Through follow-up over 17 years, the results showed that women who received basal amounts of sunlight on a regular basis had a 33% lower risk of breast cancer compared to those who never or rarely received sunlight. Epidemiological studies have shown that reduced sun exposure, with a corresponding decrease in the amount of vitamin D synthesized by the skin, increases the incidence and mortality of breast cancer, and that the average blood levels of vitamin D in breast cancer patients are lower than in women who do not have breast cancer. Based on this, it is proposed that there is a potential protective effect of vitamin D on breast cancer. Consistent with the findings of this study, serum levels of vitamin D were higher in patients with early-stage breast cancer than in patients with advanced bone metastatic disease, and this change in hormone levels occurred prior to the onset and progression of clinical disease. There are still many unanswered questions about what role vitamin D plays in cancer suppression and by what mechanism it achieves its anticancer effects, and more clinical and basic research is urgently needed to demonstrate the anticancer effects of vitamin D. Current studies have found that vitamin D can inhibit the proliferation of cancer cells and induce apoptosis and differentiation of cancer cells, and also plays an important regulatory role in the process of tumor invasion and metastasis and angiogenesis. This anti-proliferative, pro-apoptotic, anti-tumor invasive and anti-angiogenic effect of vitamin D suggests that it can be a potential therapeutic agent. However, breast cancer is not a simple class of disease and is divided into many different molecular subtypes with very different disease outcomes. This may partly explain why vitamin D has the many different functions described above in breast cancer, and the therapeutic response is very different for different types of breast cancer. In order to achieve targeted vitamin D-based therapy, a more thorough understanding of the role and function of this hormone in solid tumors is needed. Otherwise, for most breast cancer patients who may need to receive treatment related to the effects on bone calcification (e.g., starting adjuvant chemotherapy in premenopausal women or endocrine therapy with aromatase inhibitors in postmenopausal women), one of the side effects of these treatments is the impact on bone health, especially in postmenopausal patients treated with aromatase inhibitors. Patients receiving chemotherapy and breast cancer patients on endocrine therapy have a dramatic drop in estrogen levels, the latter leading to rapid loss of bone mass and osteoporosis. Estrogen upregulates 1-alpha-hydroxylase, a necessary enzyme for the conversion of circulating vitamin D into biologically active vitamin D. Thus, blocking estrogen exposes the subclinical symptoms of calcium and vitamin D deficiency and also increases the risk of bone and joint activity in patients using aromatase inhibitors. For breast cancer patients treated with endocrine therapy, especially aromatase inhibitors, regular bone densitometry and baseline levels of 25-hydroxyvitamin D should be measured and supplementation with vitamin D preparations should be appropriate. In conclusion and outlook In general, vitamin D, as a vitamin that maintains the balance of calcium and phosphorus metabolism in the body, plays a significant role in maintaining bone health, inhibiting tumorigenesis and development, and regulating the immune function of the body. Since vitamin D has so many benefits to our health, it can be replenished while basking in the sun, so we might as well participate in more outdoor activities and enjoy the health brought to us by the sun. It should be noted that vitamin D preparations are commonly used clinically to promote calcium absorption and to treat osteoporosis and rickets. However, conventional doses of vitamin D can hardly provide effective control of tumor growth, and overdose of vitamin D can cause serious adverse effects such as hypercalcemia. Therefore, researchers are developing vitamin D analogs (Analogs), which not only improve the therapeutic effects of vitamin D by hundreds, but also have no side effects such as high calcium in the body and help greatly increase calcium reabsorption in the kidneys and calcium absorption in the small intestine. This will provide new means and methods for the clinical treatment of breast cancer and other tumors, improving the efficacy and prognosis of tumor patients, and has a very promising application.