Vitamin D and calcium are well-known basic nutritional supplements for maintaining skeletal system health, and recent studies have found that vitamin D is not only limited to the traditional understanding of calcium and phosphorus regulation metabolism, it is involved in the regulation of intestinal physiology, and is related to intestinal mucosal injury diseases and intestinal tumors.
First, the intestinal absorption, metabolism and biological effects of calcium
Food is the main source of calcium. Dietary calcium is absorbed by the action of stomach acid and related enzymes, converted from insoluble complex form to free calcium.
Calcium absorption occurs mainly in the duodenum and jejunum, including active transport and passive diffusion. Active calcium absorption dependent on vitamin D receptors predominates during normal dietary calcium intake.
Dietary calcium absorbed in the intestine is mainly excreted by the kidneys, a small amount is excreted through skin sweat, and unabsorbed calcium is excreted with feces.
Vitamin D is an important regulator of intestinal calcium absorption, and in the intestine, activated vitamin D affects calcium absorption by regulating the expression of related genes.
Calcium exists in the body in two forms: bound state and ionic state, and only calcium ions have physiological activity. In addition, calcium ions are involved in processes such as blood clotting, muscle contraction, and neurotransmitter synthesis and release.
Second, the regulatory effect of vitamin D and calcium on intestinal physiology
As the main component of the digestive system, the intestine is the main place for the body to digest and absorb nutrients, and the intestine absorbs calcium ions and vitamin D, and after combining with them to be activated, it participates in regulating the growth and differentiation and physiological functions of various cells in the intestine.
1. Regulates immune effects
The intestine is the largest immune organ in the body, and about 80% of the body's immunoglobulins and 60% of immune cells are located in the intestine and function. In recent years, studies have reported that vitamin D has a variety of manifestations of its immunomodulatory effects on the gut.
(1) Vitamin D3 can promote the production of antimicrobial peptides, thereby enhancing innate immunity.
Antimicrobial peptides are neutrophil-specific granular proteins that are an important component of the host immune defense system and play an important role in protecting the integrity of the entire digestive tract mucosa and regulating the balance of microflora.
(2) Vitamin D3 acts on antigen-presenting cells, inhibits their antigen-presenting and activates the function of T cell immune response.
The antigen-presenting cells of the intestine, mainly macrophages and dendritic cells, vitamin D3 reduces the production of inflammatory cytokines, thereby suppressing their inflammatory response.
(3) Vitamin D has a regulatory effect on the immune function of T cells.
Studies have shown that vitamin D3 can inhibit the proliferation of Th cells and regulate the production of cytokines.
2. Enhance the barrier effect
From the stomach to the rectum, a layer of columnar epithelial cells is lined on its inner wall, which is an important interface between the intestinal lumen and the mucosa, and has important roles such as physical barrier, antigen presentation, and immune regulation.
There are tight junctions, adhesion junctions, and desmosomes between epithelial cells that together form a paracellular pathway that regulates intestinal permeability. Dysfunction of these connections can alter intestinal permeability and promote intestinal inflammation. Studies have shown that vitamin D3 can enhance epithelial rebuilding after injury.
3. Anti-intestinal tumor effect
CYP3A4 is a very important cytochrome oxidase, mainly expressed in liver and small intestinal epithelial cells, vitamin D can improve its metabolic activity, can greatly reduce the occurrence of intestinal tumors.
4. Regulate apoptosis
Calcium ions are important carriers for many apoptosis signal transduction, and most types of apoptosis processes rely on calcium ions. The presence of extracellular calcium is necessary for glucocorticoids to induce apoptosis of thymom cells, and some studies have found that calcium ions can reduce intracellular calcium overload and reduce apoptosis shedding.
Third, vitamin D and calcium are related to intestinal diseases
1. Inflammatory bowel disease
Inflammatory bowel disease is a group of chronic intestinal inflammations associated with intestinal microbiome disorders, genetic predisposition, autoimmune abnormalities, and more, including ulcerative colitis (UC) and Crohn's disease (CD).
There is several pieces of evidence that vitamin D may continue to influence the risk of developing inflammatory bowel disease as an environmental factor:
(1) Ecological studies suggest that the incidence of inflammatory bowel disease has a north-south gradient, that is, the incidence of inflammatory bowel disease is also increased in high latitudes, which may be related to the decrease in receiving solar ultraviolet B radiation at high latitudes, resulting in a decrease in vitamin D synthesis in human bodies, which provides evidence for the immune effect of vitamin D from an epidemiological point of view;
(2) Relevant studies have found that mice lacking 1,25-hydroxyvitamin and mice knocking out vitamin D receptors have more severe dextran sodium sulfate (DSS) colitis, and can inhibit the expression of several pro-inflammatory genes after vitamin D administration;
(3) Women with higher plasma 25-hydroxyvitamin levels are expected to have a significantly lower risk of CD.
2. Diarrheal disease
Diarrhea is a group of digestive tract syndromes characterized by increased frequency of stools and altered stool characteristics. Its etiology is complex and diverse, with infectious factors being the most common. Current studies have shown that vitamin D and calcium have a certain effect on the prevention and relief of symptoms of diarrheal diseases.
3. Intestinal tumors
A large number of research studies have proved that a high-fat diet is a risk factor for colorectal cancer. A high-fat diet can overstimulate the secretion of bile, and excess fatty acids and bile acids can cause excessive proliferation of intestinal epithelium, which becomes a trigger for colorectal cell carcinogenesis.
Calcium is believed to have a protective effect on colorectal cancer by binding bile acids and fatty acids to inactivate them or directly affect the cell cycle. Several studies have shown that higher intake of milk or dairy products can reduce the risk of colorectal cancer, especially in women, suggesting that a high-calcium diet may be a protective factor for colorectal cancer.
An analysis of prospective studies of vitamin D and colorectal cancer risk showed an inverse association between vitamin D intake and blood 25-hydroxyvitamin D levels and colorectal cancer risk.
4. Short bowel syndrome
Short bowel syndrome is a series of nutrient absorption disorder syndromes caused by various causes of small bowel resection and reduction of absorption area, such as diarrhea, malnutrition, water and electrolyte disorders, etc., which are easy to cause the deficiency of fat-soluble vitamins (D, A, K, E). In particular, patients on home parenteral nutrition are prone to a greatly increased risk of vitamin D insufficiency due to lack of light and vitamin D-rich foods.
Vitamin D and calcium are involved in the mechanisms of intestinal physiology and related diseases in terms of immune regulation, intestinal barrier, antitumor, and apoptosis regulation. The above also suggests that vitamin D and calcium supplementation may be a novel treatment for intestinal immune diseases, diarrhoeal diseases, intestinal tumors, etc.
However, there are still many questions about the clinical use of the two:
1. The therapeutic dose of vitamin D and calcium is inconclusive, and more clinical studies are needed to confirm it;
2. The current vitamin D deficiency standards for immune diseases, tumors and other diseases still follow the standards set in the early stage for rickets, in view of the certain differences in the pathophysiology of diseases, the old standards are not conducive to more accurate detection and monitoring of diseases;
3, the role of active vitamin D in regulating intestinal immunity needs to form a local high concentration environment, such as vitamin D as a therapeutic dose, will produce severe hypercalcemia, greatly limiting its use, so it is urgent (jí) to develop drugs that not only activate VDR, regulate immune response function, but also inhibit the occurrence of hypercalcemia.
Further elucidating of the mechanisms of action of vitamin D and calcium in the initiation and progression of these diseases is still needed to guide clinical application.
Reference: Vitamin D and Calcium Deficiency Related Diseases in Children Editor-in-Chief Shen Kunling Li Tingyu People's Medical Publishing House
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Source: Hanlech