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42 Benefits and Side Effects of Vitamin D (5 Contraindications To Be Noted)[Updated Feb/2023]

Vitamin D is an essential nutrient for maintaining health and a member of the steroid hormone family, which was found to prevent rickets in children in the early 20th century and is known as D because it is the fourth in the sequence of vitamins found.

Globally, its deficiency is a major public health problem affecting all age and ethnic groups, having overtaken iron deficiency as the most common nutritional deficiency in the world.

The two main subtypes, vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol), have similar effects and are not distinguished unless otherwise noted.

What are the benefits of vitamin D supplementation in empirical medicine? Are there any side effects if vitamin D supplements? See text analysis for details

 

What is Vitamin D?

Vitamin D is a micronutrient that can be metabolized into a multifunctional steroid hormone that is essential for human health, in addition to being an important part of maintaining calcium balance and bone health, it also directly or indirectly affects more than 2,<> sets of genes by binding to vitamin D receptors throughout the body (such as brain, blood vessels, prostate, breast and immune cells), but also has non-genomic rapid effects, including direct stabilizing effects on the endothelium.

Proven physiological activities of vitamin D also include: inhibition of cell proliferation and induction of differentiation, inhibition of angiogenesis, stimulation of insulin secretion, induction of apoptosis, inhibition of renin production, stimulation of macrophage production.

Current studies have also found that vitamin D deficiency is closely related to the occurrence and progression of many chronic diseases, including metabolic abnormalities, osteomalacia, osteoporosis, muscle weakness, hip fractures, diabetes, cancer, cardiovascular diseases, arthritis, and autoimmune diseases.

At present, no nutrient, drug, or hormone can be scientifically verified as much as vitamin D and beneficial to the human body. Note 1

What are the recommended proven benefits of vitamin D?

  1. Vitamin D is beneficial for COVID-19 virus infection

COVID-19 (Novel Coronavirus Disease 2019) is a respiratory infection caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which was first detected in December 2019 and as of October 12, 2022, the disease spread rapidly in countries and caused a global pandemic, with a total of more than 10 million reported cases and 19.6 million deaths.

The presentation of COVID-19 ranges from asymptomatic or mild symptoms (e.g., fever and cough) to more severe conditions (e.g., sepsis, altered consciousness, and shock), with clinical presentation clearly influenced by comorbid factors, and patients with hypertension, diabetes, cardiovascular disease, obesity, and neurological disorders may have more severe conditions.

A systematic literature review and meta-analysis (9 randomized controlled trials, 1586 people with COVID-19) showed that vitamin D supplementation reduced the risk of admission to the intensive care unit (intensive care unit) and increased vitamin D levels compared with controls. Note 1

The mechanism behind it may be vitamin D to regulate the immune response, interact with the renin-angiotensin-aldosterone system, protect endothelial function and produce antithrombotic etc.. These mechanisms reduce the risk of cytokine storms, enhance the immune response, and produce anti-inflammatory, antiviral, and antibacterial activities.

*Conclusion: Vitamin D supplementation may benefit people with COVID-19 by reducing ICU/ICU admissions, but due to the high degree of heterogeneity between included studies, more high-quality studies are needed

  1. Vitamin D is beneficial for cystic fibrosis

Cystic fibrosis is an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conduction regulatory protein (CFTR) gene, which leads to disturbances in the transport of chloride ions on the epithelial surface, resulting in abnormal thickening of mucus on the surface of the lungs, pancreas, intestines, and other organs.

It affects multiple organ systems, including the lungs, exocrine and endocrine pancreas, and gastrointestinal tract, and affects approximately 3000 in 1 live births worldwide.

Pancreatic insufficiency, which occurs in 90% of people with cystic fibrosis, and many other cystic fibrosis-related factors contribute to these patients to an increased risk of fat malabsorption and fat-soluble vitamin deficiencies.

A systematic literature review and meta-analysis (8 randomized controlled trials of 290 patients diagnosed with cystic fibrosis) noted that serum 25-hydroxyvitamin D (25OHD) levels in the intervention group performing vitamin D supplementation were significantly higher than those in the control group, but the quantitative synthesis of clinical results included: lumbar Z-score, serum bone-derived alkaline phosphatase, osteocalcin, calcium, parathyroidine, There were no significant differences in levels of the antimicrobial peptide LL-37 and albumin. Note 1

*Conclusion: For cystic fibrosis, vitamin D supplementation can only increase serum 25OHD values, and has no significant effect on clinical outcomes (e.g., bone disease, respiratory status, and immune status-related results), and is limited by the small sample size, which still needs further verification

  1. Vitamin D reduces the risk of fractures and falls

In older people, especially women, falling is a sign of poor health and decreased functioning. Fracture occurs in about 10% of falls, depending on risk factors for fall impact and bone strength.

Therefore, fall prevention is necessary to prevent fractures and reduce morbidity and mortality. Fall prevention strategies include changing environmental hazards, training paths, hip protection, and appropriate use of support tools and balance exercises. The overall prevalence of osteoporosis and low bone mass in non-institutional populations over 50 years of age in the US is estimated to be 10.3% and 43.9%, respectively.

A systematic literature review and meta-analysis (32 randomized controlled trials, 104,363 participants) noted that vitamin D3 supplementation (median daily dose of 800 IU/day, median follow-up of 24 months) was associated with a reduced risk of falls, but not fracture. Note 1

However, subgroup analyses showed that vitamin D supplementation (cholecalciferol, i.e., vitamin D3, at doses of 800 to 1,000 IU per day) was associated with a 13% and 19% lower risk of fracture and fall, respectively. In addition, daily use of vitamin D3 reduced the risk of falls, while intermittent use did not. In patients with vitamin D deficiency, vitamin D3 supplementation significantly reduces the risk of falls.

*Conclusion: Daily vitamin D800 supplementation of 1 to 000,3 IU may reduce the risk of osteoporotic fractures and falls

  1. Vitamin D is beneficial for migraines

Migraine, the second most common form of headache, is often described as a regular beating or pulsarating, moderate to severe, usually unilateral pain, lasting 4 to 72 hours, and may be accompanied by nausea, vomiting, or sensitivity to light, sound, or smell.

About one-third of patients have aura, described as progressive local neurological symptoms lasting 5 to 60 minutes, and visual aura in the form of jagged lines or diffuse flashing dark spots (vision loss) is by far the most common.

A meta-analysis (6 randomised controlled trials, 301 migraine patients) noted that vitamin D supplementation significantly reduced the number of headache attacks, headache days, and migraine disability assessment questionnaire (MIDAS) scores per month compared with controls, but had no clear effect on episode duration and severity. Note 1

*Conclusion: Vitamin D supplementation may have a positive effect on migraine, but due to small sample sizes and sample heterogeneity, more studies are needed to further validate

  1. Vitamin D is beneficial for non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease, a hepatic manifestation of metabolic syndrome (including type 2 diabetes, hypertension, insulin resistance, obesity, and dyslipidemia) (defined as the presence of ≥5% of hepatic steteaosis), is a clinicopathological condition that includes simple fatty liver, steatohepatitis, fibrosis, and cirrhosis, and is observed in individuals without evidence of excessive alcohol consumption, affecting approximately 20% to 35% of adults.

Nonalcoholic steatohepatitis (NASH), a potential variant of nonalcoholic steatohepatitis (NAFLD), occurs in 10% to 20% of people with nonalcoholic steatohepatitis, predisposing them to cirrhosis and hepatocellular carcinoma (HCC).

A meta-analysis (16 randomized controlled trials) found that vitamin D supplementation was associated with improved anthropometric and biochemical measures compared with controls: Weight, Body Mass Index, waist circumference, high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT), Fasting blood sugar, insulin, insulin resistance (HOMA-IR). Note 1

*Conclusion: Vitamin D supplementation may provide positive help in patients with nonalcoholic fatty liver disease, but limited by small sample sizes, more studies are needed to confirm the optimal dose and duration of use

  1. Vitamin D is beneficial for sarcopenia

Helicobacter pylori (Helicobacter pylori) is a gram-negative, microaerobic, spiral-shaped bacterium, which is mainly distributed in the human stomach. It is one of the most common infections in the world. The gastric mucosa of more than 50% of the global population Helicobacter pylori exists in all of them.

The loss of muscle mass and strength is inevitable during human aging. This degeneration is summarized as “Sarcopenia”, a syndrome listed in the 10th edition of the International Classification of Diseases, a musculoskeletal disorder.

The associated degradation is estimated to begin at age 40 and be detectable at about age 50, occurring at rates of 1% to 3% per year, respectively. Its progression is strongly associated with fractures, metabolic dysfunction, cardiac and respiratory disease development, mortality, and overall quality of life.

A meta-analysis of 9 randomized controlled trials involving 1420 sarcopenia participants showed that a combination of vitamin D, protein, and exercise significantly increased grip strength and showed a trend towards increasing muscle mass. Note 2

*Conclusion: The addition of vitamin D to standard treatment regimens for sarcopenia may aid functional recovery

  1. Vitamin D is beneficial for chronic urticaria

Urticaria, a rash characterized by dark red, raised, itchy lumps that affect about 15% to 20% of the population, is classified as acute urticaria (less than 6 weeks) or chronic urticaria (attacks at least twice a week for more than 6 weeks), with a female-to-male ratio of about 2:1.

Chronic urticaria can be further divided into two distinct subtypes, chronic idiopathic urticaria (lesions that occur spontaneously) and chronic induced urticaria (which requires a specific trigger, which can be medication, physical stimulation, or stress leading to the development of urticaria).

A systematic literature review and meta-analysis (17 observational studies and 5 interventional studies) suggests that urticaria populations, particularly adults with chronic urticaria, may be associated with lower serum 25(OH)D concentrations, and vitamin D supplementation can reduce severity and improve quality of life. Note 1

*Conclusion: Vitamin D supplementation may bring positive help to adults with chronic urticaria, but more studies are needed to verify due to small sample sizes and heterogeneity

  1. Vitamin D is beneficial for benign paroxysmal postural vertigo

Benign paroxysmal positional vertigo, the most common peripheral end-vestibular organ disorder, is typical of a sudden, transient sensation of rotation with characteristic nystagmus (lifetime prevalence of 2.4%, peak incidence of about 50 to 60 years, more often women, ratio approximately 2 to 1 or 3 to 1).

Symptoms are caused by changes in the position of the head and range in severity from mild dizziness to debilitating episodes that can cause nausea or vomiting and severely interfere with daily functioning.

A systematic literature review and meta-analysis (7 controlled trials involving 1133 patients with benign paroxysmal postural vertigo) suggested that vitamin D supplementation significantly reduced the recurrence of benign paroxysmal postural vertigo and improved vitamin D deficiency. Note 1

*Conclusion: For benign paroxysmal postural vertigo, vitamin D supplementation may bring positive help, but limited by small sample sizes and heterogeneity, more studies are needed to further validate

  1. Vitamin D is beneficial for sleep disorders

Insomnia is a disorder that is dissatisfied with the duration and quality of sleep, which means that it is difficult to initiate and maintain sleep, and it is easy to fall back to sleep after waking up.

Insomnia increases the risk of many health problems, such as cardiovascular disease, arterial hypertension, myocardial infarction and chronic heart failure, type 2 diabetes, cognitive impairment, depression, etc., placing a heavy burden on society and individuals.

About 30% of the world’s population suffers from insomnia, and only about 10% of patients receive appropriate treatment.

A meta-analysis (25 studies) showed that serum vitamin D levels in people with sleep disorders were often lower than normal, and vitamin D supplementation improved sleep quality (as measured by the Pittsburgh Sleep Quality Index). Note 1

*Conclusion: Vitamin D supplementation may provide positive help for sleep disorders, but more research is needed to support this due to the low quality of the available evidence

  1. Vitamin D is good for knee osteoarthritis

Osteoarthritis is the most common form of arthritis (common in weight-bearing joints such as the hands, knees, hips, feet, spine, etc.) and is characterized by the gradual disintegration of articular cartilage, the formation of new bone at the base of cartilage lesions and the edges of joints (osteophytes), and leading to chronic disability.

Most people over the age of 65 have radiographic evidence of osteoarthritis, and age, sex, weight, repetitive trauma, occupational activity, genes, sex, lower extremity dysplasia, and genetics are important risk factors for osteoarthritis manifestation.

A systematic literature review and meta-analysis (6 randomised controlled trials, 1599 people with osteoarthritis) noted that vitamin D supplementation helped improve degenerative knee arthritis scale (WOMAC) scores, including pain, function, and stiffness scores. Note 1

In the subgroup analysis, the reduction of stiffness scores was found to be most significant at vitamin D doses less than 2000 IU.

In addition, vitamin D supplementation reduced the progression of synovial fluid volume, but was not statistically significant in improving tibial cartilage volume, joint space width, and bone marrow lesions.

*Conclusion: For osteoarthritis, vitamin D supplementation may improve pain and functional status, but it is not clinically significant in preventing structural progression and requires more large, long-term trials.

  1. Vitamin D is beneficial to the prevention and treatment of pneumonia

Pneumonia is a lung infection caused by bacteria, viruses or fungi, and these syndromes can lead to different manifestations and sequelae, especially in the elderly and immunosuppressed people.

Untreated or undertreated complications of pneumonia include respiratory failure, sepsis, metastatic infection, empyema, lung abscess, and multiorgan dysfunction.

A systematic literature review and meta-analysis (13 randomized controlled trials, 4786 participants) noted that vitamin D supplementation significantly increased serum 25(OH)D levels and reduced the chance of repeated episodes of pneumonia. Note 1

Subgroup analysis showed that vitamin D supplementation had a greater effect on reducing recurrent episodes of pneumonia in trial participants with a population of children, less than 3 months of illness, and vitamin D doses greater than 300000 IU.

In addition, there was a statistically significant decrease in intensive care unit/hospitalization rates at stratified follow-up with a follow-up of less than 3 months.

*Conclusion: High-dose vitamin D intervention may reduce the chance of repeated episodes of pneumonia by enhancing immune effect

  1. Vitamin D reduces the incidence of preeclampsia

Preeclampsia is a serious pregnancy complication that affects 5% to 8% of pregnancies. It increases fetal and maternal morbidity and mortality, especially in developing countries, and is typically characterized by new-onset hypertension and proteinuria during pregnancy.

Globally, about 72000 pregnant women die each year from eclampsia and severe preeclampsia, which is the second leading cause of maternal death after bleeding.

Associated risk factors are: chronic hypertension/kidney disease, diabetes mellitus before pregnancy (10% to 35%), connective tissue disease (lupus erythematosus, rheumatoid arthritis), thrombophilia, obesity and insulin resistance, over 40 years of age, family history of preeclampsia/cardiovascular disease, small-for-gestational-age motherhood, anteuterine growth retardation in previous childbirth, placental abruption, and intrauterine fetal death.

A systematic literature review and meta-analysis (27 randomized controlled trials, 4777 pregnant women) suggested that vitamin D administration during pregnancy reduced the risk of preeclampsia (by about 63%), and that the risk was further reduced by supplementation up to 20 weeks’ gestation. Note 1

In addition, subgroup analyses showed that the reduction in risk values was independent of the duration of supplementation (until delivery), type of intervention (vitamin D alone or in combination with calcium), maternal age, and study design.

*Conclusion: Vitamin D supplementation during pregnancy can help reduce the risk of preeclampsia, but more precisely designed studies are needed to confirm optimal doses

  1. Vitamin D is beneficial for autism

Autism Spectrum Disorder is a group of neurodevelopmental disorders in which people may have difficulty expressing and understanding certain emotions, difficulty understanding the emotions of others, expressive language disorders, abnormal eye contact, preference for minimal changes, limited access to toys, and preference for playing in isolation (about 90 to 250 per 10,000 people suffer from autism)

According to the main symptoms of children, autism spectrum disorder is made up of different subgroups, including autistic disorder, Asperger syndrome, and pervasive developmental disorder.

A meta-analysis (3 randomized controlled trials of 203 children with autism spectrum disorder) suggested that vitamin D supplementation improved the typical symptoms of autism spectrum disorder (as measured by scores on the Social Response Scale and the Autism Rating Scale in Children). Note 1

*Conclusion: Vitamin D supplementation may have a positive effect on improving autism in children, but limited by small sample sizes, more large trials are needed to support this

  1. Vitamin D is beneficial for chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease is an obstructive respiratory disease with clinical manifestations including dyspnea, chronic cough, low exercise capacity, tinnitus, bronchial infection, and later weight loss.

Smoking is a major risk factor for COPD, with at least 30.60% of people aged 20 to 7 years with normal lung function and persistent smoking developing moderate COPD, compared with 3.6% of non-smokers.

Risk factors for COPD in nonsmokers include asthma, advanced age, low educational attainment, occupational toxin exposure, and history of childhood airway infection.

A meta-analysis of 25 randomized controlled trials with 2,670 patients with COPD suggested that vitamin D treatment improved measures of lung function assessment (FEV1, FEV1/FVC), a 6-minute walk test (6MWT), acute exacerbation, sputum production, and chronic obstructive pulmonary disease assessment scale (COPD). Assessment test) score. Note 1

*Conclusion: Vitamin D supplementation may provide positive benefits in COPD, but more research is needed

  1. Vitamin D is beneficial cancer events

Cancer is the leading cause of death worldwide, second only to heart disease. Associated cancer risk factors such as smoking, alcohol consumption, UV exposure, human tumor virus infection, chronic diseases such as obesity and type 2 diabetes.

It is estimated that one in two people will develop cancer in their lifetime, a figure that was one-third at the turn of the century, and fortunately, some cancer types, particularly colorectal, breast, and prostate cancer, can be detected through routine screening, allowing for early detection of malignant lesions.

A Pooled Analysis (2 cohort studies of 2,304 women over the age of 55) showed that 25(OH)D greater than 40 ng/ml reduced the risk of cancer by 67% compared with those with blood concentrations of 25(OH)D less than 20 ng/ml (vitamin D deficiency). Note 1

Another meta-analyses (64 observational studies, 44,165 cancer cases) pointed out that higher blood vitamin D values (25OHD) were associated with lower cancer mortality and the rate of disease progression, and vitamin D receptor gene variants also contributed to the prognosis of cancer events. Note 2

A meta-analysis (10 randomized controlled trials with 81,362 participants) suggested that vitamin D supplementation reduced cancer mortality (but did not help cancer incidence), and that the effect was most pronounced in people with no history of cancer and additional vitamin D or calcium supplementation. Note 3

*Conclusion: Vitamin D deficiency is associated with higher cancer incidence and poor prognosis, and cancer-related mortality may be reduced through supplementation

  1. Vitamin D is beneficial for tuberculosis

Over the past 200 years, an estimated 10 billion people have died from tuberculosis, which infects a third of humans and is the leading cause of infectious death worldwide, comparable to the impact of HIV.

People with smear-positive tuberculosis are the most common source of TB infection because when they cough or sneeze, they excrete small droplets carrying infectious bacilli, and an untreated person with infectious TB can infect 10 to 15 people per year.

A meta-analysis (5 randomized controlled trials, 1126 tuberculosis participants) noted that vitamin D supplementation did not shorten the time to sputum culture and smear transformation, nor did it increase the proportion of people with negative sputum culture. Note 4

However, in the participant subgroup of the TaqI tt genotype, it shortened the time to sputum culture switching and increased sputum culture conversion in MDR-TB.

*Conclusion: Overall, vitamin D supplementation has no clear benefit in anti-TB treatment

  1. Vitamin D is beneficial Helicobacter pylori infection

Helicobacter pylori (Helicobacter pylori) is a gram-negative, microaerobic, spiral-shaped bacterium, mainly distributed in the human stomach, is one of the most common infections in the world, more than 50% of the world’s population has the presence of Helicobacter pylori in the gastric mucosa.

Helicobacter pylori colonization can lead to chronic gastritis in all infected people, most infections are asymptomatic, although long-term infection increases the risk of site-specific disease. Between 10% and 15% of infections result in peptic ulcers, and 95% of duodenal ulcers and 80% of stomach ulcers are associated with Helicobacter pylori.

A meta-analysis (10 studies) noted that patients who tested positive for Helicobacter pylori had lower vitamin D levels. Note 5

In addition, patients who successfully eradicated Helicobacter pylori had higher vitamin D levels, while those who lacked vitamin D had a higher failure rate for Helicobacter pylori eradication.

*Conclusion: Vitamin D may be an important protective factor against Helicobacter pylori infection, but more studies are needed to verify the results

  1. Vitamin D is beneficial for gestational diabetes

Gestational diabetes mellitus, defined as glucose intolerance of any degree first detected during pregnancy, is a disease specific to pregnancy and is estimated to affect 7 in 1 live births worldwide.

Risk factors associated with maternal age, obesity, ethnic background, history of fetal macrosomia, past adverse pregnancy outcomes, family history of polyhydramnios type 2 diabetes, and history of gestational diabetes mellitus.

A systematic literature review and meta-analysis (6 randomized controlled trials involving 454 pregnant women diagnosed with gestational diabetes in the second or third trimester) suggests that vitamin D supplementation may reduce neonatal complications such as hyperbilirubinemia, compared with placebo or no treatment, Polyhydramnios and the need for maternal and infant hospitalisation (but limited by small sample sizes, the evidence is low). Note 6

*Conclusion: To date, there is no high-quality evidence that vitamin D supplementation in gestational diabetes mellitus improves glucose metabolism and maternal and infant related complications

  1. Vitamin D is beneficial blood lipid regulation

Serum lipid profile is an important indicator for predicting cardiovascular disease risk and has become a routine detection method for cardiovascular disease.

The test includes four basic parameters: total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. Common abnormalities can be divided into elevated plasma low-density lipoprotein, elevated plasma triglycerides, and decreased plasma high-density lipoprotein.

A systematic literature review and meta-analysis (41 randomized controlled trials, 3434 participants) noted that vitamin D supplementation improved serum total cholesterol, LDL cholesterol, and triglycerides (but no significant improvement in HDL cholesterol). Note 1

In addition, improvements in total cholesterol and triglycerides were more pronounced in participants with vitamin D deficiency.

*Conclusion: For hyperlipidemic subjects with vitamin D deficiency, additional supplementation may have a positive help in blood lipid regulation

  1. Vitamin D boosts male hormones (androgens)

Male hormones, also known as androgens, or male sex hormones, are defined as substances that develop and maintain masculine characteristics in reproductive tissues, particularly the reproductive tract, secondary sex characteristics, and fertility, and contribute to the anabolic state of body tissues.

Testosterone is one of the main androgens in the mature male mammalian cycle and is associated with testicular decline, spermatogenesis, penis and testicular enlargement, increased libido, hair type, voice changes, and deeper voice.

Testosterone levels decline with age, with decreased testicular size, decreased libido, decreased bone density, decreased muscle mass, increased fat production, and decreased red blood cell production.

A systematic literature review and meta-analysis (8 with 1061 adult male participants) noted that vitamin D supplementation (daily doses ranging from 600 IU to 4000 IU to 60,000 IU per week for 6 to 144 weeks of intervention) had an effect on total testosterone and sex hormone-binding globulin) had no significant effect. Note 1

*Conclusion: To date, there is no evidence to support vitamin D supplementation to increase male hormones, but limited research and possible conjuring factors require more large randomized controlled trials to support this

  1. Vitamin D reduces low birth weight and small gestational age birth events

Low birth weight is defined by the World Health Organization as a birth of less than 2.5 kg. It is estimated that 15% to 20% of newborns worldwide are born with low birth weight each year.

In addition, low birth weight and small gestational age may increase the risk of intracranial haemorrhage, respiratory distress, sepsis, blindness, gastrointestinal disease, long-term neurological dysfunction, language development disorders, impaired academic performance, cardiovascular disease, and diabetes due to immaturity of multiple organ systems.

A systematic literature review and meta-analysis (including 13 randomized controlled trials) found that maternal vitamin D supplementation during pregnancy (alone and not in combination with other micronutrients) reduced the risk of low birth weight and small for gestational age, in addition to positive effects on birth weight, length and head circumference. Note 1

*Conclusion: Vitamin D is an essential nutrient for fetal growth and development, with a positive effect on neonatal size, and due to the limited number of studies, more research is needed to further evaluate the influence of genetic, environmental, sociodemographic, and lifestyle factors.

  1. Vitamin D helps lose weight

Overweight and obese, the result of an imbalance in daily energy intake and expenditure, lead to excessive weight gain and are the second leading preventable cause of death after smoking.

Overweight and obesity are defined in terms of body mass index (BMI), which is body weight (kg) divided by height squared (m), and a healthy BMI ranges from 18.5 to 24.9 kg/m2. Overweight is defined as a BMI between 25 and 29.9 kg/m2 and obesity as a BMI of ≥ 30 kg/m2.

A systematic literature review and meta-analysis (11 randomized controlled trials, 947 overweight and obese adult participants) found that vitamin D supplementation reduced body mass index (-0.32 kg/m2) and waist circumference (-1.42 cm), but had no significant effect on weight measures. Note 1

The mechanism behind it may be related to vitamin D inhibition of parathyroid hormone, support intestinal calcium absorption, and stimulate insulin receptors.

*Conclusion: Vitamin D supplementation may provide positive benefits for weight loss, but due to the heterogeneity of the included studies, more studies are needed to confirm its clinical benefit

  1. Vitamin D prevents cardiovascular disease

Cardiovascular diseases refer to all diseases related to the heart and circulatory system.

These disorders can be caused by modifiable or non-modifiable factors such as smoking, physical activity, healthy diet, blood pressure, weight, glucose and cholesterol levels

Immodifiable factors such as age, sex, family history, and especially first-degree relatives with onset before age 55 (male) or 65 (female) (e.g., atherosclerotic disease) are considered independent genetic risk factors.

A meta-analysis (21 RCTs with 83,291 participants) noted that vitamin D supplementation was not associated with a reduction in major adverse cardiovascular events compared with placebo, nor with secondary measures of myocardial infarction, stroke, cardiovascular mortality, or all-cause mortality. Note 1

*Conclusion: To date, there is no evidence that vitamin D supplementation reduces the incidence of cardiovascular disease

  1. Vitamin D is beneficial for multiple sclerosis

Multiple sclerosis, a chronic inflammatory demyelinating disease of the central nervous system, is common in residents of high latitudes and has a higher risk of disease in women than men (sex ratio 2.5:1).

It causes secondary macrophage aggregation and subsequent destruction of the myelin sheath and is considered an autoimmune disease. All neurological functions (motor, cerebellum, brainstem, sensory, sphincter, vision, mental state) can be impaired during an attack.

A Cochrane Database Systematic Review (12 randomized controlled trials with a total of 933 multiple sclerosis patients) noted that Vitamin D supplementation had no significant effect on the improvement of annualised relapse rate, Expanded Disability Status Scale, and gadolinium-enhancing T1 lesions. Note 1

*Conclusion: To date, oral vitamin D has not been significantly helpful in improving multiple sclerosis, but more studies are needed to confirm its clinical benefit due to the high risk of bias of the included studies

  1. Vitamin D is beneficial asthma improvement

Bronchial asthma, also known as asthma, is a chronic inflammatory disease of the respiratory tract characterized by recurrent episodes of wheezing, difficulty breathing, chest tightness, and coughing, usually at night or early in the morning.

It is characterized by bronchial hyperresponsiveness and variable airflow obstruction, which is often reversible, either spontaneously or through treatment.

About 10% of children and 5% of adults suffer from bronchial asthma. The greatest risk factor is ectopic constitution, for example, related to a genetic predisposition to produce IgE antibodies against pollen, dust mites, fungi, or proteins of animal origin.

A meta-analysis of 14 randomized controlled trials with 1421 asthmatic patients noted that vitamin D supplementation significantly reduced the rate of asthma exacerbation (up to 27%). Note 1

In subgroup analyses, the improvement in rate of asthma exacerbation was most significant in vitamin D insufficiency (vitamin D < 30 ng/ml).

The improvement in forced expiratory volume in first second (FEV1%) was significantly associated with vitamin D insufficiency and airflow restriction (defined as FEV1% < 80%)

*Conclusion: Vitamin D may be positively helpful in improving asthma, especially in vitamin D deficient populations, but more studies are needed to support potential interfering factors such as small sample size and clinical heterogeneity

  1. Vitamin D beneficial for severe depression

Major depression disorder is one of the most common mental illnesses, also known as clinical depression.

In the United States, about 7 to 9 percent of adults experience an episode of major depressive disorder once a year, and an estimated 800 million people meet the criteria for major depressive disorder.

Although the physiological factors that trigger the development and progression of major depressive disorder are unknown, bed studies have shown that changes in the effectiveness of monoamine neurotransmitters (eg, norepinephrine, dopamine, serotonin) and differences in receptor regulation are associated with the disease.

Other psychosocial factors such as social isolation, stressful living circumstances, and lack of support/trust relationships can also increase the risk of depression.

A systematic literature analysis (including 4 randomized controlled trials, 948 patients with severe depression) noted that vitamin D supplementation had a favorable effect on depression scores, with a pooled mean effect size of 0.58, indicating a moderate degree of effect. Note 1

*Conclusion: For patients with severe depression, vitamin D supplementation can bring positive help, but limited by small sample sizes and methodological bias, more studies are needed to support this

  1. Vitamin D beneficial for type 2 diabetes

Diabetes is a major health problem worldwide that causes serious complications and disabilities, and is a chronic, progressive metabolic disorder characterized by hyperglycemia, mainly caused by an absolute (type 1 diabetes) or relative (type 2 diabetes) deficiency of the hormone insulin.

It is believed that a calorie-high Western diet combined with a sedentary lifestyle is the main cause of type 2 diabetes.

A literature review and meta-analysis (71 observational studies) found that vitamin D status was significantly negatively correlated with blood glucose levels in diabetic and non-diabetic subjects, and that hypovitaminosis D increased the risk of hyperglycemia and type 2 diabetes. Note 1

A meta-analysis (28 randomized controlled trials) suggests that vitamin D supplementation (average daily dose of 3500 IU for 6 months) improves glycaemic control (HbA1c and fasting blood glucose) and reduces insulin resistance in pre-diabetic or high-risk people with diabetes, although effects may vary by age, calcium intake, vitamin D deficiency, and serum 25(OH)D levels. Note 2

A literature review and meta-analysis (20 randomized controlled trials) pointed out that vitamin D supplementation significantly improved serum 25(OH)D levels and insulin resistance index (HOMA-IR) in patients with type 2 diabetes, especially in non-obese subjects, Middle Eastern ethnic groups, vitamin D deficiency, better baseline glycemic control, and patients taking large doses (daily dose of 2000 IU) in a short period of time. Note 3

*Conclusion: Vitamin D deficiency increases the incidence of type 2 diabetes, and in some conditions, additional supplementation can improve glycemic control in existing patients and reduce the incidence of disease in high-risk groups

  1. Vitamin D reduces the rate of preterm birth

Preterm birth is generally defined as any delivery before the completion of pregnancy at 37 weeks. The global preterm birth rate is currently 11.1%, but varies by geography and ethnicity, ranging from more than 15% in parts of Africa, 5-6% in some European countries, and possibly even lower in parts of East Asia.

The causes of preterm birth are complex, however, some predisposing factors have been identified, including: antepartum haemorrhage, placental abruption, uterine hyperdistension, cervical insufficiency, hormonal changes, bacterial infections, and inflammation.

A literature review and meta-analysis (6 randomized controlled trials and 18 observational studies) suggested that maternal blood 25-OHD deficiency (25-OHD value less than 50) was associated with an increased risk of preterm birth, and that vitamin D supplementation during pregnancy alone reduced the risk of preterm birth by 43%. Note 1

The mechanism behind this is related to vitamin D to improve preterm birth-related precipitating factors, such as infection, inflammation and oxidative stress.

*Conclusion: Vitamin D deficiency in pregnant women increases the risk of preterm birth, and vitamin D supplementation alone can reduce the associated risk value

  1. Vitamin D is beneficial polycystic ovary syndrome

Polycystic ovary syndrome is the most common endocrine disorder in women, with a prevalence of nearly 5% to 10% in women of childbearing age.

The disease is characterized by elevated adrenal androgen secretion by the ovaries, and common symptoms include hirsutism, menstrual irregularities, acne, anovulatory infertility, hair loss, and polycystic ovaries, accompanied by other metabolic abnormalities, including dyslipidemia, insulin resistance, and hypertension.

A meta-analysis (17 studies) found that blood 25OHD concentrations and insulin sensitivity were significantly lower in patients with PCOS. In addition, additional vitamin D supplementation lacked response (serum parathyroid hormone concentration, insulin resistance, insulin sensitivity did not change). Note 1

Another meta-analysis (9 randomized controlled trials, 502 people with PCOS) suggested that vitamin D supplementation may benefit follicle development (with more dominant follicles) and menstrual cycle regulation. Note 2

A recent meta-analysis (including 7 randomized controlled trials) suggests that vitamin D supplementation in women with PCOS significantly reduces sensitivity C-reactive protein, malondialdehyde, and total antioxidant capacity) level (but no significant change in nitric oxide total glutathione (GSH) content). Note 3

*Conclusion: Compared with the general population, patients with PCOS have a lower blood concentration of 25OHD, and additional supplementation may have a positive help for the condition

  1. Vitamin D is good for the elderly’s exercise ability (walking speed)

Walking speed is a simple, objective and overall measure of lower extremity neuromuscular function and physical performance that reflects the subject’s health, disease, fitness and emotional state.

Walking speed decreases with age, while slower walking increases the risk of falls, hospitalization, and subsequent physical and cognitive decline, and can also be used to predict survival.

Gait speed above 1.0 m/s is an important indicator of community life and participation, reflecting the ability to perform activities of daily living.

In contrast, gait velocities less than 0.6 m/s are considered unusually slow and are associated with a decline in independent functioning.

A systematic literature review and meta-analysis (24 observational studies with 51 to 4100 older adults) showed that blood vitamin D concentrations of 25OHD were significantly associated with walking speed in older adults, and that those with severe vitamin D deficiency, deficiency and insufficiency walked significantly slower than those with normal values. Note 1

*Conclusions: 25OHD concentration is positively correlated with walking speed in older people, and walking speed is significantly slower in those with deficiency or insufficiency, but more research is needed to confirm whether supplementation can bring improvement

  1. Vitamin D improves lower back pain

Low back pain is a common condition that up to 84 percent of adults experience in their lifetime, and is the second leading cause of labor loss, linked to about $500 billion a year spent in the United States.

Low back pain may be related to many underlying factors, such as nerves, muscles, fascial structures, bones, joints, discs, and organs within the abdominal cavity.

Acute attacks usually refer to less than 2 to 4 weeks in duration, 12 weeks in subacute, and more than 12 weeks in chronic cases.

A meta-analysis (8 clinical trials, 3,534 participants) found that vitamin D had no significant effect on improving symptoms of lower back pain compared with any intervention (placebo, no intervention, or other pharmacological intervention), even after stratified analysis (type of back pain, supplement). Note 1

*Results: Vitamin D supplementation did not confer a clear benefit on lower back pain and further confirmation is needed due to the small sample size and heterogeneity of the included studies

  1. Vitamin D is beneficial atopic dermatitis

Atopic dermatitis is a chronic or recurrent inflammatory skin disease characterized by pruritic papules (with serous exudates) that sometimes exfoliate and lichen-like epidermis, and are usually curved in distribution.

Although the pathophysiology of atopic dermatitis is not fully elucidated, it is thought to be the result of a combination of epidermal barrier dysfunction, immune dysregulation, and environmental factors, with common triggers including food allergies, heat, sweating, anxiety, depression, and infection.

One observational study (in 60 patients with atopic dermatitis) found that vitamin D levels were inversely correlated with the severity of atopic dermatitis in children. Note 1

A meta-analysis (including four randomized controlled trials) suggests that vitamin D supplementation has a potentially important role in improving symptoms of atopic dermatitis compared with placebo and can be considered a safe and acceptable treatment option. Note 2

The mechanism behind it may be related to the immunomodulatory effect of vitamin D, the formation and restoration of skin barriers, the reduction of transcutaneous water loss, and the promotion of the production of antimicrobial peptides of keratinocytes, macrophages and neutrophils.

*Conclusion: For subjects with atopic dermatitis with vitamin D insufficiency, additional supplementation can help relieve symptoms, however, due to genetic, environmental, and other confounding factors, more precisely designed experiments are needed for further validation

  1. Vitamin D is beneficial for blood pressure regulation

Hypertension is the most common cardiovascular disease in middle-aged and middle-aged people, and early detection and self-management are the key to affecting the prognosis of the disease.

Vascular and organ complications associated with hypertension include stroke, retinopathy, coronary heart disease/myocardial infarction and heart failure, proteinuria and renal failure, as well as vascular lesions and atherosclerotic changes.

A meta-analysis (30 randomized controlled trials, 4744 participants) pointed out that the effect of vitamin D3 supplementation on blood pressure will vary according to dose, treatment regimen, trial time and population composition, with daily doses of more than 800 IU and people over 50 years of age having the most antihypertensive benefits (whether healthy or hypertensive). Note 1

*Conclusion: Vitamin D3 supplementation may have the effect of lowering blood pressure in middle-aged and middle-aged and older people, but more experiments are still needed for further verification

  1. Vitamin D is beneficial for female hair loss

Female Pattern Hair Loss usually refers to diffuse non-scarring alopecia, which is the main symptom of thinning hair at the top of the head, less affecting the forehead hairline, and the age of onset is 20 to 30 years old (12%) and women over 70 years old (55%).

The causes of female pattern hair loss may be mainly related to genetic susceptibility, iron deficiency and hormonal imbalance, and are often referred to as female male baldness.

A case-control study of 45 female hair loss patients found that those with lower blood levels of vitamin D3 had higher rates of female hair loss compared with healthy people. Note 1

*Comment: Vitamin D3 deficiency is associated with female pattern hair loss, and more research is needed to confirm whether supplementation can bring benefits

  1. Vitamin D reduces the incidence of cognitive dysfunction

Cognitive function is unique to a few species, the ability to interact with the outside world, such as memory, language, recognizing objects, making plans, etc., and any function such as disappearance or gradual degradation is called cognitive impairment.

If there are two or more cognitive impairments that seriously affect the ability to live and work, it can be defined as dementia.

A meta-analysis (7 studies, 6068 participants) pointed out that insufficient blood vitamin D concentrations (25OHD ≤20 ng) significantly increased the risk of cognitive impairment in the elderly, especially in semantic memory and time direction (25OHD greater than 20 ng mL reduced the risk of cognitive impairment by 14.1%). Note 1

The mechanism behind it may be related to vitamin D’s ability to protect neural networks, regulate neurotrophic factors, regulate inflammation, promote neuronal vitality and function, and reduce amyloid plaque accumulation.

*Conclusion: According to the Asian population survey, insufficient blood vitamin D concentration is positively associated with cognitive dysfunction

  1. Vitamin D reduces cold events: acute respiratory infections

Respiratory tract infections, which are mainly caused by bacterial, viral or fungal infections of the respiratory tract (nose, throat and lungs), are the most important public health problems due to their easy transmission and high morbidity.

Symptoms range from mild symptoms of the common cold, laryngitis, pharyngitis, tonsillitis, acute rhinitis, acute sinusitis, acute otitis media, to potentially fatal acute bronchitis, pneumonia, and tracheitis.

A systematic literature review and meta-analysis (25 controlled studies with 11,321 participants) suggested that vitamin D supplementation helped reduce the risk of acute respiratory infections. Note 1

In subgroup-analysis, it was found that the protective effect was more obvious for those who regularly supplemented the habit (and especially for objects with 25-hydroxyvitamin D less than 25 nmol/L).

*Summary: Regular supplementation with appropriate doses of vitamin D can help reduce the incidence of acute respiratory infections (colds).

  1. Vitamin D improves breast cancer prognosis and mortality

Breast cancer is the first aggressive malignant tumor in female cancer, and the main risk factors include: first-degree genetic inheritance, breast tissue density, previous benign breast biopsy results, oral contraceptive use, reproductive age, etc., and the risk of cancer with individual factors increases by 1 to 2 times.

The relationship between vitamin D deficiency and cancer has long been confirmed by many studies Note 1A recent prospective cohort study also pointed out that breast cancer patients with a blood concentration of 25-hydroxyvitamin D in the first third will improve the overall survival rate by about 30% compared with the bottom third of the population. Note 2

The related survival improvement effect was even more obvious in premenopausal women, showing that vitamin D plays an important role in cancer prevention and prognosis.

  1. Vitamin D is beneficial fatigue phenomenon

Fatigue seems to be commonplace for busy modern people, but if left unchecked and the underlying causes are not thoroughly identified, it will lead to various psychosomatic disorders in the long run.

And everyone must have their own commonly used anti-fatigue therapies, such as bathing, listening to music, eating food, massage, etc., but unfortunately, most of these have no scientific basis.

A double-blind controlled study (4 weeks, 120 healthy but vitamin D deficient patients/25(OH)D < 20 micrograms/L) significantly improved the fatigue assessment scale compared with placebo. Note 18

That is, the degree of improvement in fatigue is greater. These changes are also correlated with increased levels of 25(OH)D in the blood.

  1. Vitamin D is good for bowel irritability

Irritable bowel syndrome is a condition characterized by abdominal pain, bloating, diarrhea, constipation, and intestinal peristalsis disorders.

According to surveys, the prevalence of this disease in women is twice that of men, and the more economically developed countries, the higher the incidence rate, reaching about 2% of the total population.

Due to complex causes (psychological factors, abnormal intestinal peristalsis, intestinal infection, inflammation, immune disorders, etc.), some clinical drugs often fail to achieve the desired effect, so many alternative therapies have emerged.

A double-blind controlled study (6 months, sample size of 90 people) noted that vitamin D (50 000 IU taken every other week) helped improve symptoms (including abdominal pain, flatulence, abdominal sound, global gastrointestinal symptoms) in people with irritable bowel.Note 1

In addition to symptom improvement, there was also significant improvement in IBS severity score system and quality of life score (compared to placebo).

  1. Vitamin D reduces the incidence of schizophrenia

Schizophrenia is a brain disease related to cognitive, emotional, thinking and other mental disorders, patients often have unrealistic thoughts and behaviors, which in turn affect interpersonal relationships, work and self-care ability, because it is more common in young people, so it is also called juvenile schizophrenia.

Studies have pointed out that people with vitamin D deficiency have a higher incidence of schizophrenia (the mechanism behind it may be related to vitamin D can regulate PRODH/proline dehydrogenase and reduce proline concentration) Note 7

*Proline is a neuromodulator, and high concentrations are positively correlated with IQ decline, cognitive impairment, and relapse rates of schizophrenia and hospitalization

Another study in women also found that consuming more vitamin D in the diet significantly reduced psychotic-like symptoms by 37%. Note 8

  1. Vitamin D affects the mortality rate of hospitalized patients

The vast majority of people only understand what a disease is and what it is after they get sick. Although the care of the hospital can save your life, but usually there is no emergency, whether to go to the hospital, it is usually not easy to decide, especially the elderly usually have an established impression of the hospital, feel that after entering the hospital, it is difficult to come out.

A paper (NEJM) published in the New England Journal of Medicine examined the association between vitamin D concentrations and mortality in patients in the Intensive Care Unit.

It was found that vitamin D deficiency had a mortality rate of up to 45% (compared to 16% in normal cases), suggesting that vitamin D deficiency increased overall mortality in acute hospitalized patients by a factor of 3. Note 11

In addition, recent studies have continued to confirm this thesis. A study of 135 intensive care unit patients found that vitamin D concentrations below 12 ng/mL were associated with a 32.2% risk of death, compared with 13.2% above this value, a nearly 2.5-fold difference. Note 12

Nevertheless, studies have shown that high-dose vitamin D supplementation during hospitalization does not bring immediate protective effect, which indicates that to achieve the above mortality reduction effect, it must be based on a continuous basis, that is, the level of vitamin D in the body must be maintained at ordinary times.

  1. Vitamin D reduces the chance of stridor and asthma in offspring

Wheeze is a high-pitched whistling sound that is the most common symptom of asthma in children five years of age and younger, occurring when the small airways are narrowed by bronchospasm, swelling of the lining of the mucosa, excessive secretions, or inhalation of foreign bodies, and are usually heard on exhalation due to severe airway obstruction.

Stridor in young children can also be caused by inflammation or anatomical abnormalities, so not all stridor bronchitis will progress to wheezing.

A literature review and meta-analysis (7 studies, 6068 participants) pointed out that the vitamin D intake of pregnant women during pregnancy showed a nonlinear U-shaped curve relationship with stridor and asthma events and occurrence of offspring, and the daily dose was about 800 IU with the most protective effect. Note 1

*Conclusion: Vitamin D intake during pregnancy may help reduce the incidence of stridor and asthma in offspring

How is vitamin D supplemented? How is the dosage and intake determined?

How much vitamin D you need depends on many factors. These factors include age, ethnicity, latitude, season, sunshine, clothing, etc.

According to the Institute of Medicine (IOM), the current recommended daily intake of vitamin D is 400 IU to 800 IU, or 10-20 micrograms, but this is too low for adults.

Most adults increase their risk of vitamin D deficiency due to inadequate sun exposure and overuse of sunscreen.

Therefore, most studies suggest that supplementation of at least 30 IU or 25 to 1000 IU per day is required to achieve optimal serum levels above 1500 ng/ml for 2000 (OH) D.

 

When to take vitamin D?

One study of the relationship between dietary fat mass and vitamin D absorption rate supplementation found that plasma vitamin D3 spike levels combined with fat-containing diets were about 32% higher than those in the control group without fat-containing diets, but the fat form did not affect absorption. Note 1

This means that vitamin D supplementation can be done at any time, and taking it with meals can improve absorption

Are there any side effects of vitamin D supplementation?

While most people have no problem taking vitamin D supplements, overdose is also possible.

According to the Institute of Medicine, 4,000 IU is the safe upper limit for an adult’s daily vitamin D intake. However, daily doses up to 10,000 IU have not been shown to cause toxicity in healthy individuals. Note 1

However, ingestion of 40,000 to 100,000 IU (1000-2500 mcg) per day for more than 1 month has been shown to be toxic to humans

This is 10-25 times the recommended upper limit of dose. Blood levels of 25(OH)D, which generally produce vitamin D toxicity, are usually higher than 150 ng/ml (375 nmol/L).

That is, taking vitamin D causes toxicity, usually when taking 40,000 IU per day for several months or more, or when taking a large dose at a time.

When 25(OH)D levels are too high, this causes calcium levels in the blood to rise, creating a condition called hypercalcemia.

Early symptoms of hypercalcemia include nausea, vomiting, diarrhea, constipation, loss of appetite, and fatigue, and other symptoms include muscle weakness or pain, excessive thirst, altered consciousness, hypertension, renal tube calcification, renal failure, or hearing loss.

Vitamin D toxicity is usually reversible and can be recovered by avoiding sun exposure and stopping all diet and supplements, but in severe cases kidney failure and arterial calcification (usually irreversible).

Safety precautions

    1. In some rare diseases, even if your body has low levels of vitamin D and you do not consume too much vitamin D, you may develop hypercalcemia. If you have the following diseases, it is best to confirm with your doctor before supplementing with vitamin DThese include primary hyperparathyroidism, granulomatomatous diseases, sarcoidosis, tuberculosis, and lymphoma
    2. Pregnant or breastfeeding women should not take excessive amounts of vitamin D (daily dose should not exceed 4000 IU), which may lead to hypercalcemia, epilepsy in young children, developmental delay and other problems
    3. Do not combine with cholesterol-lowering statin drugs (such as Lipitor) and calcium channel blockers for hypertension (may affect drug absorption)
    4. Do not use in combination with psoriasis medication Calcipotriene and arrhythmia medication (Digoxin) (may cause hypercalcemia)
    5. Long-term use of steroid drugs (Corticosteroids) may cause osteoporosis, patients should pay special attention, or discuss the possibility of calcium or vitamin D supplementation with their doctors

Medications that may reduce vitamin D absorption (talk to your doctor about supplementing them if you are taking these medications)

Antiepileptic drugs, antacids, antibiotics (Rifampin), diet drugs (Orlistat), antibiotic acid sequestrants (Bile acid sequestrants)

Drugs that may increase vitamin D absorption

Diuretics (Thiazide), estrogen, tuberculosis drugs (Isoniazid)

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