Manufactured in the skin as a response to ultraviolet light and is obtained from the diet.
Vitamin D is classified as a fat-soluble vitamin and is synthesized in the skin from dietary or endogenous cholesterol when an individual is exposed to sunlight or ultraviolet radiation.
For most people, the major source of vitamin D is the formation cholecalciferol (vitamin D 3) in the skin in response to exposure to ultraviolet B light exposure.
Oral supply of vitamin D is not essential provided patients are exposed to sufficient amounts of sunlight.
Only a certain amount of vitamin D may be absorbed at a given time by the body, and spending more time in the sun does not get more vitamin D.
Vitamin D levels can vary between seasons.
The amount of UV exposure a person requires is determined by the time of year, UV levels, skin type, and vitamin D levels.
Up to 50% of the world’s population may not get enough sun.
Low vitamin D levels are more common in some people, such as those with naturally dark skin or those who get very little sun exposure.
When discussing vitamin D levels, health professionals will refer to a type of vitamin D known as Calcidiol – which is also called 25-hydroxyvitamin D and shortened to 25(OH)D.
UV-B radiation enters stand and converts 7-dehydrocholesterol to previtamin D3, which is rapidly converted to vitamin D3, the only naturally occurring form of vitamin D in humans.
Vitamin D is produced by photo chemical conversion of 7-dehydrocholesterol to cholecalciferol (vitamin D3) in the skin or is acquired through the diet as either cholecalciferol or ergocalciferol (vitamin D2)..
Diet alone, with the exception of supplemental fluids and cold water fish is a poor source of vitamin D.
Dietary supplements contain either vitamin D3 (cholecalciferol) or the yeast derived vitamin D2 (ergocalciferol) which cannot be made by humans.
After ingestion vitamin D2 and D3 are converted by the liver’s vitamin D-25-hydroxylase to 25-hydroxyvitamin D and then by kidneys’ 1 alpha hydroxylase to the active form 1,25 hydroxyvitamin D.
1,25-dihydroxy vitamin D is the form of vitamin D that is the active hormone which stimulates calcium uptake from the intestine.
The differences between vitamins D2 and D3 do not affect metabolism, both function as prohormones, and when activated exhibit identical responses in the body.
Vitamin D is a fat-soluble vitamin.
The extent to which sun exposure is sufficient depends on the season, time of day, cloud and smog cover, skin melanin content, and whether sunscreen is worn.
Acts as a pro-hormone and effects hormone balance and immune regulation of the body.
The primary biologic function of vitamin D is to maintain normal blood levels of calcium and phosphorus.1,
Most foods, unless they are fortified, are poor sources of vitamin D.
Vitamin D plays a role in calcium absorption into the bones.
Vitamin D deficiency is relatively common, with an estimated prevalence between 19% and 77% in the United States.
An estimated 42% of Americans have a vitamin D deficiency, according to statistics presented by the Cleveland Clinic in 2018.
A study of 80% of more than 200 patients hospitalized with COVID-19 had a vitamin D deficiency.
A deficiency in vitamin D can result in a softening of the bones called osteomalacia or a bone abnormality called rickets.
Vitamin D deficiency may be associated with:
Weakened immune system
Seasonal depression
Autoimmune disease
Cancer
Osteopenia
Eczema and psoriasis
Dementia
Proximal muscle weakness.
Cardiovascular disease
All-cause mortality.
Vitamin D supplementation and outcomes of various diseases have been mixed or not definitive.
Recommendations define vitamin D insufficiency as 12-20 ng/mL (30-50 nmol/L) and a deficiency as a serum 25OHD concentration less than 12 ng/mL (30 nmol/L).
The USPSTF concluded the current evidence is insufficient to assess the balance of benefits and harms of screening for vitamin D deficiency in asymptomatic adults.
In a clinical trial of adults treated with vitamin D for three years iat doses of 4000 IU per day or 10,000 IU per day compared with 400 IU per day: there was no significant differences in bone strength and did not result in improved bone health (Burt LA).
Vitamin D deficiency seen in those who live in northern regions with little sunlight, people with dark skin, people on low fat diets and those taking steroids and weight loss medications.
Vitamin D is a globally prevalent condition associated with multiple adverse health outcomes including mortality.
An inverse relationship between serum 25-hydroxvitamin D, and all cause mortality for 25(OH)D values up to 20-36 ng/mL.
Higher cardiovascular, cancer and respiratory mortality associated with low vitamin D status.
Vitamin D supplementation is not associated with a reduction in major cardiovascular events, myocardial infarction, stroke, cardiovascular disease mortality, or all-cause mortality.
Administration of high-dose vitamin D3 does not provide an advantage over placebo with respect to 90 day mortality or other, non-fatal outcomes among critically ill, vitamin D-deficient patients (National HeartLung and Blood Institute).
Among asymptomatic community dwelling populations with low vitamin D levels, the evidence suggests the treatment with vitamin D has no effect on mortality, incidence of fractures, falls, depression, diabetes, cardiovascular disease, cancer, or adverse events, physical functioning or infections.
Early administration of high dose enteral vitamin. D does not provide advantage over placebo with respect to 90 day mortality or other non-fatal outcomes among critically ill, vitamin D deficient patients.
The RDA for vitamin D is 600 IU/day and the Daily Value is 400 IU.
Recommended dietary allowances for vitamin D ate 600 to 800 IU per day, corresponding to a total 25-hydroxy vitamin D level of at least 20 ng/mL to meet the bone health needs for 97.5% of the population.
Others suggest vitamin D intake of at least 800 to 2000 IU per day for adults 50 years of age or older to attain 25-hydroxy vitamin D levels of at least 30 ng/mL.
Vitamin D Rich Foods
Sunlight promotes vitamin D synthesis from cholesterol in the skin.
Cod liver oil 1 tsp: 440 IU (over 100% DV)
Sardines 3 ounces: 164 IU (41% DV)
Salmon 3ounces: 400 IU (100% DV)
Mackerel 3 ounces: 400 IU (100% DV)
Tuna 3 ounces: 228 IU (57% DV)
Raw Milk 1 cup: 98 IU (24% DV)
Caviar 1 oz: 33 IU (8% DV)
Eggs 1 large: 41 IU (10% DV)
Mushrooms: 1 cup: 2 IU (1% DV)
To prevent Vitamin D deficiency: getting sunlight, consume 2 of these vitamin D rich foods daily.
Vitamin D deficiency has been connected to obesity and difficulty losing weight.
Surveys have shown at 5% of the population one year old had very low 25-hydroxy vitamin D levels less than 12 ng/mL, and 18% had levels between 12 and 19 ng/mL.
One study found that women who had higher levels of vitamin D on a calorie-controlled diet lost more weight than those with lower levels of the vitamin.
Unclear if vitamin D deficiency causes obesity or if obesity leads to vitamin D deficiency. .
Studies have found that healthy levels of vitamin D reduce cancer risk especially for cancer of the colon and breast.
Women who consume higher levels of vitamin D – particularly from dietary sources – have a reduced risk of developing early-onset colorectal cancer, compared with those who have lower levels.
2018 published study Vitamin D Assessment Randomized Clinical Trial-high-dose vitamin D supplements does not decrease cancer risk.
Low vitamin D levels are associated with poor survival in a prospective study of women with breast cancer (Yao S et al).
In the above study breast cancer prognosis was most prominently affected among premenopausal women with low vitamin D levels.
Older adults with adequate vitamin D levels are more likely to be active, have improved muscle strength, and are less prone to falls.
2 forms of naturally occurring Vitamin D: Cholecalciferol, vitamin D3 from animal sources and ergocalciferol, vitamin D2 from plant sources.
Most Vitamin D in the circulation is produced naturally when 7-dehydrocholesterol in the skin is exposed ultraviolet B radiation to produce vitamin D3.
Vitamin D is first converted to 25(OH)D, the major circulating metabolite, by 25-hydroxylases is in the liver.
25(OH)D undergoes a second hydroxylation in the kidney into 1,25 dihydroxyvitamin D (1,25(OH)2D), by a one-alpha-hydroxylase.
1,25(OH)2D, 1,25 dihydroxyvitamin D is also known as calcitriol and it is the biologically active form of vitamin D exerting its action by binding to an intracellular receptor, the vitamin D receptor.
Cholecalciferol is converted to 25-hydroxyvitamin D (1:25-OH-D), or calcitriol by the tissues that utilize it.
Vitamin D levels are most frequently measured as serum levels of 25-OH- D due to its long half-life of 2-3 weeks.
Calcium supplements have risks and side effects, and are not likely indicated for most healthy community-dwelling adults over 50.
Taking vitamin D supplements does not protect against fractures in people over 50
living in the community.
VITAL study of 25,871 participants supplementation with vitamin D did not result in a lower incidence of invasive cancer or cardiovascular events than placebo.
Observational studies show association between low serum levels of vitamin D an increased risk of cancer and cardiovascular disease, yet supplements have not resulted in improvements.
In a randomized clinical trial of daily high-dose vitamin D supplementation for 5 years reduced the incidence of advanced cancer in the overall cohort of adults without a diagnosis of cancer at baseline, with strongest risk reduction in individuals with normal weight.
There is no evidence that the use of vitamin D3 in adults prevents depression.
The best diet for calcium this is a Mediterranean-style diet rich in colorful plants, plenty of legumes, and fish, and this plus high-protein, low-fat, and low-sugar dairy can supply plenty of calcium.
People who are likely to be deficient in vitamin D includes people with eating disorders; people who have had gastric bypass surgeries; those with malabsorption syndromes like celiac sprue; pregnant and lactating women; people with dark skin; and those who wear total skin covering.
Individuals are at risk for a dropped in vitamin D levels during the long, dark winter months.
Supplement of anywhere from 400 to 2,000 IUs of vitamin D daily is not likely to cause harm.
Vitamin D toxicity is usually seen at levels above 80 ng/ml, which causes excessive calcium to be released into the bloodstream.
Vitamin D toxicity is characterized by hypercalcemia, hyperphosphatemia, suppression of parathyroid hormone, and it is usually observed when intakes exceed the range of more than 50,000 to 1,000,000 international units of vitamin D per day and is maintained long-term for several months to years.
The intake of 4000 international units per day of vitamin D is considered the highest dose that is safe, but a metanalysis showed that daily vitamin doses of 2354 international units were associated with 50% increase in the risk of hypercalcemia.
Vitamin D insufficiency is widespread and affects approximally 75% of postmenopausal women.
Vitamin D status is defined by circulating concentration of 25-hydroxyvitamin D.
1, 25-OH-D as a half-life of 3-4 hours in the blood.
The active metabolite 1,25-hydroxyvitamin D is involved in calcium and phosphorus homeostasis.
Vitamin D deficiency may be categorized as mild, moderate, or severe.
Calcidiol is the next-to-last step in the metabolism of vitamin D and is used as a marker because it is easier to measure than the concentration of calcitriol, the final step.
Mild vitamin D deficiency is defined as serum calcidiol concentration of 25 to 50 nmol/L.
A serum calcidiol concentration of 12.5 to 25 nmol/L indicates a moderate vitamin D deficiency, and at those levels the incidence of hypocalcemia and rickets increases.
Serum calcidiol concentration of less than 12.5 nmol/L, indicates a severe deficiency.
The vitamin D receptor is expressed in multiple issues including skeletal muscle, brain, breast colon and immune cells.
Vitamin D receptors belong to a supra-family of the nuclear receptors for steroid hormones and helps regulate gene expression by acting as a ligand- activated transcription factor.
The activation Vitamin D receptors maintains extracellular calcium levels and influences up to 200 genes that mediates cellular growth, cellular differentiation, and apoptosis.
Vitamin D status is evaluated by measurement of the inactive metabolite 25-hydroxyvitamin D in serum.
The best indicator of total body vitamin D stores is 25(OH)D because his half-life is for greater than vitamin D or 1,25 (OH)2D.
The serum 25(OH)D concentration reflects sunlight exposure primarily, since foods at little vitamin D.
25-50% or more of adults are deficient in vitamin D.
Vitamin D. consists of two bioequivalent forms-vitamin D2 (D2), ergocalciferol, obtain from dietary vegetable sources and oral supplements, and Vitamin D3 (D3), cholecalciferol, which is obtained primarily from skin exposure to ultraviolet B radiation from sunlight, ingestion of food sources, including fish, milk, juices, margarines, yogurts, cereals, soy, and oral supplements.
Vitamin D content of most foods is between 50-200 IU per serving, with the exception of oily fish, which is a rich source of vitamin D.
Vitamin D2 and vitamin D3 biologically inert.
Following gastrointestinal absorption of vitamin D2 and D3 they are metabolize to 25-hydroxyvitamin D {25(OH)D} in the liver: 25 (OH)D2 and 25(OH)D3.
25 hydroxy vitamin D, 25(OH)D, is also called calcidiol is converted to 1, 25- dihydroxyvitamin D {1,25(OH)2D} also known as calcitriol, in the kidney and other tissues by 1a-a hydroxylase enzyme.
The effects of vitamin D are exerted by calcitriol via activation of vitamin D receptors in the cells.
In the absence of adequate sun exposure vitamin D deficiency may occur rapidly, and other risk factors for vitamin D deficiency include obesity, low dietary intake, dark skinned, lack of sun exposure, and older age.
Deficiency of vitamin D may occur among residents in sunny locations due to cultural and clothing styles.
The elderly produce 75% less of vitamin D3 than young individuals.
The use of sunscreen reduces cutaneous vitamin D production.
Properly applied sunscreen reduces vitamin D synthesis by 95%.
For most people vitamin D is primarily obtained by cutaneous production as a result of exposure to the sun.
UBV radiation from the sun varies from the time of day, the season, latitude, altitude, skin pigmentation, clothing, age and the use of sunscreen.
If sunlight exposure is limited, the daily recommended dose of vitamin D is insufficient.
The goal of serum level of 25-OH-D for skeletal health is 30 ng/dL.
Excess vitamin D with levels more than 150 ng female is associated with renal stones and hypercalcemia.
Higher levels in persons with multiple sclerosis are associated with lower degree of MS activity, magnetic resonance imaging lesion load, brain atrophy, and disease progression in patients treated with Betaseron (Ascherio A et al).
For patients with 25-OH-D levels of less than 20 ng/dL a vitamin D3 (cholecalciferol) supplement should be initiated at least 2000 international units orally daily and ergocalciferol (vitamin D2) could be used at the same dose and schedule.
Data suggest vitamin D therapy improves cardiovascular health.
Vitamin D supplementation may help in the prevention of falls, and hip fractures among seniors 65 years of age and older at high-risk of vitamin D deficiency.
Vitamin D supplementation may improve lower extremity function, although monthly high dose of Vitamin D treatment had no benefit on lower extremity function and was associated with increased risk of falls (Ferrari HA et al).
Prospective studies indicate lower serum concentrations of 25-hydroxyvitamin D levels associated with increased risk of hip fracture, myocardial infarction, cancer and death.
Low levels of 25-hydroxyvitamin D may be a modifiable risk factor for certain chronic illnesses.
Pregnant and lactating women and their neonates are at high risk of vitamin D deficiency.
Up to 69% of pregnant women have vitamin D levels in the insufficient range.
Low levels of 25-hydroxyvitamin D consistently associated with increased risk of clinical subclinical coronary heart disease.
Low 25-hydroxyvitamin D levels are associated with high blood pressure levels in cross-sectional studies and associated with increased rates of incident hypertension.
Vitamin D receptors are found on endothelial cells, smooth muscle cells, and myoc yes and vitamin D improve endothelial function in some studies reducies pro-inflammatory cytokines, reducing activity of the renin-angiotensin-aldosterone system and reduces parathormone levels.
Vitamin D supplementation is ineffective in lowering blood pressure and should not be used as a antihypertensive agent (Beveridge LA et al).
1, 25-dihydroxyvitamin D, the active vitamin D hormone produced from 25 (OH)D suppresses the renin-angiotensin system, modulates immune function, and reduces chronic inflammation, and inhibits abnormal cell proliferation.
Has two major anti-inflammatory effects: the first anti-inflammatory effect reflects the fact that 25 (OH) D is metabolized locally in monocytes and macrophages 1,25 dihydroxyvitamin D.
1,25 dihydroxyvitamin D interacts with its vitamin D receptor in activated B lymphocytes to modulate immunoglobulin synthesis and reduce production of auto immunity related antibodies.
1,25 dihydroxyvitamin D binds its nuclear vitamin D receptor in activated T lymphocytes effecting cytokine production and inducing T1 lymphocyte transformation into T2 lymphocytes.
The second anti-inflammatory effect indicates the endothhelium is activated and destabilized during inflammation and vitamin D stabilizes endothelial membranes.
Children and adults with asthma with a serum vitamin D level of this than 30 ng/mL have been linked to airway hyperresponsiveness, impaired lung function, increased exacerbations and reduce corticosteroids responsiveness.
Vitamin D supplementation during the prenatal period does not influence the six-year incidence of asthma and recurrent wheeze among children who were at risk for asthma.
A study of low serum 25 (OH)D concentration was associated with increased risk of coronary heart disease events among white and Chinese participants but not among black or Hispanics (Robinson-Cohen C et al).
Patients with chronic kidney disease frequently develop deficiency of 1, 25-dihydroxyvitamin D3 ( calcitriol) because of a lack of its precursor 25-hydroxyvitamin D3, and impaired activity of the kidney enzyme 1aplha hydroxylase, which converts this precursor to the active hormone (Quarles LD et).
Altered vitamin D metabolism can lead to secondary hyperparathyroidism, which is the primary indication for calcitriol therapy.
Chronic kidney disease adversely effects on vitamin D metabolism, with a reduction in the renal reserve of the enzyme 1-alpha-hydroxylase.
Vitamin D deficiency is common in chronic kidney disease, with 70-80% of patients with stage 3-5 disease having such a deficiency.
Observational studies in chronic kidney disease indicate association with vitamin D deficiency and increased risk of cardiovascular events and between therapy with calcitriol and related analogues and reduced cardiovascular events.
PTH effect on the kidney is also the stimulation of the conversion of 25-hydroxy vitamin D into 1,25-dihydroxy vitamin D (calcitriol), which is released into the circulation.
Vitamin D deficiency is associated with mortality in non critically ill populations.
Low vitamin D levels contribute to osteoporosis by decreasing total fractional calcium absorption, secondary hyperparathyroidism, increased bone resorption, and decreased bone mineral density.
Experts disagree on the optimal vitamin D level for skeletal health, some contending 20 mg per mL and others 30 ng per mL.
In African-American men, vitamin D deficiency was associated with increased odds of prostate cancer diagnosis on biopsy.
Severe vitamin D deficiency was positively associated with higher Gleason grade and tumor stage.
Vitamin D deficiency had a significant association with aggressive tumor characteristics in men with newly diagnosed prostate cancer.
A 25-hydroxyvitamin D (25-OH D) <12 ng/mL more than tripled the likelihood that the biopsy would reveal a high Gleason score and doubled the odds for a higher disease stage.
Among African-American men, low serum 25-OH D also increased the odds of prostate cancer diagnosis.
As compared with their European-American counterparts, African-American men have a 60% greater risk of developing prostate cancer and more than a twofold greater risk of dying of the disease.
Vitamin D deficiency has a higher prevalence in northern latitudes, older people, and African Americans.
Some evidence also has suggested an inverse association between prostate cancer and UV radiation exposure in the U.S.
African-American men with positive prostate biopsies had significantly lower mean 25-OH-D level where as non-African-American men did not.
Among European-American men tested, the investigators found no associations between vitamin D status and prostate cancer diagnosis.
There is an association between 25-OH-D level and Gleason grade on biopsy.
Men who were vitamin D deficient also were more likely to meet NCCN criteria for high risk and very high risk as opposed to low and intermediate risk.
The same analyses of African-American men showed a significant association between serum 25-OH-D <20 ng/mL and a positive prostate biopsy.
In a randomized clinical trial among critically ill patients with vitamin D deficiency the administration of high-dose vitamin D3 compared with placebo did not reduce hospital length of stay, mortality, or six-month mortality (Amrein K et al).
In a randomized trial maintaining serum 25(OH)D levels of 30 ng/mL or higher in postmenopausal
women did not effect bone or muscle outcomes (Hansen KE et al).
Vitamin D supplementation during pregnancy is not decrease the risk of childhood asthma.
In a multinational double-blind randomized placebo-controlled trial among 227 patients with chronic kidney disease, mild to moderate left ventricular hypertrophy, preserved left ventricular ejection fraction 48 weeks of therapy with paicalcitriol did not alter left ventricular mass index or improved measures of diastolic dysfunction (The PROMO Randomized Controlled Trial).
Patients with vitamin D deficiency with levels less than 12 ng/dL more who are symptomatic should be started at a higher daily doses, or weekly dose of 50,000 international units is commonly used.
Acts on the innate immune system, increasing production of human cathelicidin antimicrobial peptide , modulates cytokine responses, and improves T cell helper balance.
Can enhance clearance of bacteria, strengthen epithelial barriers to infection, and enhances function of antigen presenting cells.
Solar UV-B with wavelengths 290-315 nm radiation is the primary source for most people.
Approximately 15 minutes daily exposure to sunlight required to receive a therapeutic dose of vitamin D.
Maximum cutaneous synthesis of vitamin D can be equivalent to an oral vitamin D 3 intake of 10,000 international units a day (HolickMF).
Sources of cutaneous synthesis or dietary intake occur typically intermittently.
Irregular intake of vitamin D can lead to chronic vitamin D insufficiency.
Deficiency reported to occur in all age groups, in all geographic areas and in all seasons.
Dietary sources include salmon (400 IU per 3.5 oz), mackerel, sardines, cod liver oil (400 IU/tsp) and egg yolks (20 IU).
Sources include fortified milk, orange juice, and cereals, with small amounts in tuna, salmon, mackerel, beef liver, cheese, egg yolks and some mushrooms.
Normal diet contains little vitamin D.
U.S. Institute of Medicine recommends 200 IU daily for women aged up to 50 years, 400 IU for women aged 51 to 70 years, and 600 IU for women aged 71 years and older.
Minimum daily requirement up to 600 IU.
Endocrine Society recommends at least 1500 to 2000 IU of vitamin D per day to achieve 30 ng per mill of 25 (OH)D.
Endocrine Society recommends 4000 to 6000 international units of vitamin D per day to reduce all cause mortality at a level of 40-60 ng per mL of 25(OH)D.
For obese patients 2 to 3 times more supplementation of vitamin D is required.
The US Preventative Services Task Force recommends against using supplements of vitamin D and calcium to prevent fractures: in the review of six randomized trials there was no evidence of benefit from taking 400 international units of vitamin d3 and 1000 mg of calcium daily, but one in every 273 women who took supplements for at least seven years developed kidney stones.
In a random I was study of postmenopausal women with vitamin D deficiency to take placebo, 800 IU vitamin D2, or high dose of vitamin D regimen to achieve in 25 hydroxyvitamin D levels greater than or equal to 30 mg/ mL: results had no data to support the recommendation to maintain serum 25 (0H)D levels of at least 30 ng/mL in postmenopausal women in order to optimize musculoskeletal health (Hansen KE et al).
24% of patients with 25-OHD levels less than than 10 ng/ml have had a recent respiratory tract infection compared with 20% with levels of 10 to less than 30 ng/ml and 17% with levels of 30 ng/ml or more.
Randomizedclinical trials have not shown that vitamin D supplementation improves health, except in person with high risk of falling with decreased risk of falls.
The Institute of Medicine recommends that to prevent adverse bone outcomes most children and adults consume 600 international units to 800 international units of vitamin D daily and achieve 25-OHD levels of at least 20 ng/ mL.
Western diets supplemented with vitamin D in milk and vitamins.
Supplementation with lower daily doese of vitamin D (400 IU of vitamin D3 orvles) and calcium 1000 mg calcium carbonate do not preven fractures in postmenopausal women (USPSTF).
In the above study i in 273 women who take such doses will develop kidney stones by 7 years.
Deficient in human milk.
Milk is fortified with 100 IU per 8 oz., some cereals with 100 IU per serving, yogurt with 100 IU per serving and orange ice with 100 IU pr 8 oz.
Represents 2 forms: vitamin D2 (ergocalciferol) comes from irradiation of the yeast and plant sterol ergosterol, and vitamin D3 (cholecalciferol) which is found in fish oils and cod liver oil and is made in the skin.
Essential for calcium homeostasis.
Decreases the risk of falling because the active vitamin D metabolite 1,25-hydroxyvitamin D binds to a nuclear receptor in muscle tissue resulting in improved muscle function.
Where dietary intake is poor, and in cloudy climates, in the presence of excessive body covering, prolonged nursing and poor diet intake of the elderly deficiency is common.
Worldwide prevalence may be more than 40% of the population.
Deficiency is common in elderly and associated with increased risk of fracture.
Deficiency associated with greater risk of developing vascular disease in patients with hypertension (Wang).
Deficiency estimated to be present in 1 billion people worldwide.
Deficiency associated with mortality in non critically ill populations.
Low vitamin D status is a significant factor associated with disease severity, mortality, or a shorter survival time in the ICU.
Among critically ill patients with vitamin D deficiency administration of vitamin D3 did not reduce hospital length of stay, hospital mortality, or six-month mortality (Amrein K et al).
National Health and Nutrition Examination Survey (NHANES) analyzed 25-dihydroxyvitamin D in 9757 children and young adults, aged 1 to 21 years and found 9% had vitamin D deficiency with 25 dihydroxyvitamin D of less than 15 ng per mL and 61% had vitamin D insufficiency with 25 dihydroxyvitamin D of 15-29 ng per milliliter (Kumar J).
The NHANES study indicated that vitamin D deficiency was associated with elevated parathyroid hormone levels, higher blood pressures, lower serum calcium levels, higher glucose concentrations, and lower high-density lipoprotein levels compared with patients with sufficient vitamin D levels (Kumara J).
Low levels of vitamin D associated with overweight status and abdominal obesity in 3577 fasting nonpregnant adolescents aged 12-to 19 years, participating in the NHANES study of 2001-2004.
Deficiency defined as a level of 25-dihydroxyvitamin D below 15 ng/mL
Deficiency in 1100 ICU patients is highly prevalent, and is associated with adverse outcome independently of hypocalcemia and hypoalbuminemia (Lee P).
Association of vitamin D deficiency with increased rates of pneumonia and upper respiratory tract infections in children.
Seasonal variation in 25-hydroxyvitamin D levels mirrors the seasonality of respiratory tract infections.
There is a inverse association between 25-OHD levels and recent upper respiratory tract infections.
In the study of 1100 ICU patients 17% had undetectable levels of Vitamin D (Lee P).
Deficiency associated with individuals with dark skin, older people, shut-ins and for those living farther away from the equator.
Deficiency noted to be present in up to half of healthy middle aged and older adults.
Some studies suggest low levels of vitamin D correlate with poor prognosis in breast cancer patients (Palmieri C).
It is suggested that an inverse relationship exists between total average annual sunlight energy that strikes the ground and age-adjusted breast cancer mortality.
Inverse associations have been suggested between serum 25-hydroxyvitamin D levels and breast cancer development, risk for recurrence, and mortality in women with early stage breast cancer.
Vitamin D deficiency associated with shorter time to treatment and shorter overall survival in chronic lymphocytic leukemia.
A meta- analysis vitamin D and breast cancer risk, and a randomized trial of vitamin D supplementation did not demonstrate benefits (Gissel T, Chlebowski RT).
15 minutes of exposure to daily sunlight maintains a good vitamin D supply.
Supplementation and calcium for individuals at risk for vitamin D insufficiency reduce risk of fracture, but not in all studies.
Randomized clinical trial’s have not shown that vitamin D supplementation improves health, except in some studies it may decrease the risk of falling.
In 11 trials vitamin D is associated with 11% decrease risk of falls.
400-800 IU daily by itself has little effects on bone mineral density, except among individuals with vitamin D deficiency.
Supplementation studies reveal a dose response curve for vitamin D that is relatively linear up to 10,000 international units of vitamin D 3 per day.
Necessary for skeletal growth during infancy and childhood.
Sub optimal status common among healthy young children.
Supplementation of premature infants with vitamin D in the first year of life is associated with increased whole body mass at 12 years of age.
Vitamin D is important during periods of rapid bone mineral accrual.
Infants that are nursing are susceptible to vitamin D deficiency because vitamin D in breast milk is limited.
Recommendations are for 400 international units (10 �g) per day based on maintenance 25-hydroxyvitamin D concentrations in the range of 75-115 nmol per liter (30-60 ng/mL).
Only 5-36% exclusively breast-fed infants receive supplemental vitamin D and poor adherence is a major determinant of vitamin D deficiency in breast-fed infants.
The Institute of Medicine’s recommendations for infants is 400 international units/day but 25 hydroxyvitamin D concentrations range between 40 and 50 nmol per liter or 16-20 ng/mL.
In a double-blind randomized clinical trial among 132 1 month old healthy, term, breast-fed infants a vitamin D supplement dosage of 1600 IU/D was able to increase plasma 25 hydroxyvitamin D concentration to 75 nmol/L or greater in 97.5% of infants at three months (Gallo S et al).
More than 200 human genes contain vitamin D response elements.
Involved in the regulation of gene expression for cellular proliferation, differentiation, apoptosis and immune mechanisms.
Insufficiency is common in healthy pregnant women and risk of osteoporotic fracture later in life is increased by adverse environment during early development, including intrauterine life.
Activation of vitamin D requires adequate exposure of vitamin D from diet or by sunlight exposure, an intact intestine via which calcium and vitamin D is absorbed, and an intact liver with which to convert vitamin D to 25-hydroxyvitamin D and an intact kidney to convert 25-hydroxyvitamin D to 1, 25(OH)2D.
Lower levels in African Americans because darker pigmentation hampers vitamin D synthesis by the skin.
Excess intake associated with nausea, vomiting and weakness and can cause hyperkalemia, calcium deposition in the kidney and other soft tissues and may be associated with arrhythmias and impaired mentation.
A meta-analysis of nine studies of vitamin D supplementation revealed a significant reduction in mortality (Autier).
Use an anti-fracture agent is uncertain as two 2007 Meta-analyses concluded that vitamin D may not reduce fractures significantly or may do so only in combination with calcium, and primarily among institutionalized older patients (Porthouse J, Grant AM, Jackson D).
A meta-analysis in 2007 by Tang and others concluded that calcium with or without vitamin D may reduce total fracture risk by 12%.
Another meta-analysis by Bischoff-Ferrari revealed that calcium supplementation alone had a neutral effect on non-vertebral fractures and a possible adverse effect on hip fracture risk.
The US Dept. of Health and Human services in a meta-analysis did not support a significant reduction of fractures with vitamin D supplementation and suggested that the benefits of vitamin D may depend on additional calcium and may be primarily seen in institutionalized individuals.
Vitamin D sufficiency is associated with lower rates of adverse health conditions.
Most randomized trials examining vitamin D supplementation are negative.
Vitamin D deficiency may increase risk for several major health disorders, but supplementation may not reduce risk in deficient patients if doses are inadequate.
Autier and colleagues found that vitamin D deficiency is associated with cardiovascular diseases, inflammation, glucose metabolism disorders, infectious diseases, mood disorders, declines in cognitive function, and even all-cause mortality.
With the exception of colorectal cancer, adequate levels of vitamin D do not appear to reduce the risk of developing various types of cancer.
Vitamin D adequacy is associated with a lower risk of cardiovascular events by up to 58%, diabetes by up to 38%, colorectal cancer by up to 33%, and all-cause mortality by 29%.
Higher vitamin D levels is associated with better survival in metastatic colorectal cancer.
The largest trial was the Women’s Health Initiative (WHI), which included 36,282 postmenopausal women. The women were given 10 mcg of D3 per day for 84 months:
Autier et al concluded that low concentrations of 25(OH)D were associated with a variety of acute and chronic health disorders through the inflammatory process involved with disease.
Trials have not proved low dose vitamin D supplementation reduces the risk of disease occurrence and progression.
The Institute of Medicine now recommends that everyone should be on 600 IU of vitamin D, and to treat vitamin D deficiency, 2,000 to 3,000 IU of vitamin D per day.
The use of cholecalciferol (vitamin D) does not improve knee pain or cartilage volume loss in patients with severe knee osteoarthritis.
Vitamin D supplements had no impact on the pain of knee osteoarthritis (OA).
A dose response relationship exists between vitamin D and fracture reduction with data showing a significant trend between serum 25-hydroxyvitamin D concentrations, and hip bone density and lower extremity strength.
50,000 IU of ergocaliferol weekly for 8 weeks effectively treats vitamin D deficiency, and continued treatment with the same dose every other week for up to 6 years prevents recurrent deficiency in most patients, yet 16% of patients remin deficient or insufficient (Pietras SM ).
10,000 international units of vitamin D3 for 4 months daily in patients with metastatic breast cancer to bone is safe and reduces inappropriate elevations of parathormone level caused by long-term bisphosphonates (Amie E).
Low concentrations of 25-hydroxyvitamin D (25[OH]D) are most likely an effect of health disorders and not a cause of illness.
Moderate to strong associations between lower concentrations of 25(OH)D and higher risk for conditions ranging from cardiovascular disease to infectious disease, glucose-metabolism disorders, and mood disorders.
No effect on disease occurrence as a result of vitamin D supplementation in randomized clinical trials, including 34 intervention studies involving vitamin-D supplementation of patients with low 25(OH)D concentrations (Autier P et al).
In interventional studies involving 2805 individuals, patients with a baseline mean 25(OH)D concentration less than 50 nmol/L and supplementation with 50 �g/day of vitamin D resulted in no significant improvement in health status.
It is speculated that lower 25(OH)D concentrations in people with illness is disease-related inflammation.
Among hospitalized patients with Covid-19, a single high dose of vitamin D3 compared with placebo did not significantly reduce hospital length of stay and it�s use is not supported for the treatment of moderate to severe COVID-19.
A meta-analysis of vitamin-D supplementation showed no effect on HbA1c levels.
While data showed that high 25(OH)D concentrations were associated with a protective effect on colorectal cancer, 2 large intervention trials showed no reduced risk of any cancers, including colorectal, with vitamin-D supplementation.
One exception has been seen in the elderly population, mainly women, who showed a slight reduction in all-cause mortality if they received vitamin-D supplementation of 20 mg/day, but the authors speculate that the improvement could be related to vitamin-D deficits caused not directly by the illness itself but by lifestyle changes resulting from the illness.
Bitamin D supplementation does not result in significant lower risk fractures than placebo among generally healthy midlife and older adults who are not selected for vitamin D deficiency, low bone mass, or osteoporosis (LeBofg MS).
An estimated 42% of Americans have a vitamin D deficiency, according to statistics presented by the Cleveland Clinic in 2018.
A study showed 80% of more than 200 patients hospitalized with COVID-19 had a vitamin D deficiency.
In a cohort study of 4638 individuals with a measured vitamin D level in the year before undergoing COVID-19 testing, the risk of having positive results in Black individuals was 2.64-fold greater with a vitamin D level of 30 to 39.9 ng/mL than a level of 40 ng/mL or greater, decreasing by 5% per 1 ng/ mL increase in level among individuals with a level of 30 ng/mL or greater.
There were no statistically substantial correlations between vitamin D levels with COVID-19 positivity rates in White individuals.
The habitual use of vitamin D supplements is substantially correlated with a 34% lower risk of COVID-19 infection.
Circulating vitamin D levels at baseline or genetically predicted vitamin D levels were not linked with the risk of COVID-19 infection.
The investigators concluded that their findings imply that habitual use of vitamin D supplements is related to a lower risk of COVID-19 infection.
Hospitalized patients with COVID-19 and low vitamin D levels could have a decreased risk of dying or needing mechanical ventilation if they obtain at least 1000 units of vitamin D supplementation weekly.
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