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Product Review: Vitamin D Supplements Review (Including Calcium, Vitamin K, Magnesium)
 


Posted: 4/4/15 Last Update: 3/25/17Vitamin D Supplements Reviewed By ConsumerLab.com

Sections: Jump to a section by clicking on its name.
Summary: What You Need to Know About Vitamin D Supplements
  • There are many reasons to make sure you're getting sufficient vitamin D: These include improved bone health, reduced risk of heart attack and stroke, reduced risk of asthma and allergy, reduced inflammation, and perhaps others. Not surprisingly, over given periods of time there are fewer deaths among people who have the right amount of vitamin D compared to those who have too little or too much. For details, see What It Does >>
  • You may already get enough vitamin D from the sun (about 15 minutes to the face, arms, and hands at least twice a week without sunscreen) and the foods you normally eat. If you're not sure, get your blood level checked by your doctor. A total serum 25-hydroxyvitamin D level of at least 20 ng/mL is considered "sufficient," although there may be additional benefit to being in the 25 to 35 ng/mL range. Don't exceed 39 ng/mL. Be aware that people who are black generally have lower total vitamin D levels than whites, but new research suggests these lower levels may be sufficient for blacks. For details see How Much Do You Need and How Much is Too Much? >>
  • If your level is below 20 ng/mL, try to get more sunshine. If that's not possible or you are dark-skinned, get more vitamin D from fortified foods or supplements. Vitamin D2 or D3 will raise your vitamin D level, but D3 is preferable as it may raise levels more effectively over time and is less likely to cause erroneously low vitamin D blood test results.
  • How much to take? For every 1 ng/mL increase, you'll need to get an additional 100 IU of vitamin D per day (obese individuals may require double the amount). For example, if your blood level is 18 ng/mL, taking 400 IU of vitamin D daily (or 800 IU if you are obese) should get you to about 22 ng/mL. It can take 6 weeks to reach the peak. Keep taking the vitamin D to stay at that level. For details, see What to Consider When Using >>
  • Don't overdo it! Studies show that people with the highest levels of vitamin D actually tend to have more bone fractures, fall more frequently, sleep less well, and die sooner than those with lower, but sufficient, levels. If your level is over 20 ng/mL, you probably don't need a supplement. If your level is above 35 ng/mL, taking a supplement may be doing more harm than good, so consider cutting back. For details see How Much Do You Need and How Much is Too Much? >>
  • Choose a supplement that has been Approved by ConsumerLab.com in the table below because not all supplements live up to their ingredient claims. Also, compare prices (see the last column of the table) -- you can get some good products for just pennies a day (for specific examples see What CL Found -- Cost >>)
  • Take vitamin D supplements with your biggest meal of the day (the one that contains most fats and oils) as this can increase absorption by as much as 50%! For details, see Take Vitamin D with Food >>
What It Is:
Vitamin D is a fat-soluble vitamin. There are two major forms of vitamin D: D2 (ergocalciferol) and D3 (cholecalciferol). Both vitamin D2 and D3 appear to be absorbed with equal efficiency and, at moderate doses, are equally able to raise levels of 25-hydroxyvitamin D, the hormonally active form of vitamin D and a clinical measure of vitamin D status. However, at very high doses, D3, may be more efficient at raising 25-hydroxyvitamin D levels.

Vitamin D2 is made by the conversion of a sterol found in plants and yeast. Vitamin D2 is used in some dietary supplements.

Vitamin D3 is produced naturally in human skin exposed to ultraviolet B light and occurs in some animal products, such as cod liver oil, and, in smaller amounts, in other fatty fish such as herrings, mackerel, sardines, and tuna. Vitamin D3 is the most common form used in dietary supplements and is the form generally used to fortify foods such as milk (which naturally contains a small amount of vitamin D3). Vitamin D3 is made by the conversion of cholesterol compounds, such as 7-dehydroxycholesterol from lanolin found in sheep's wool.

See ConsumerTips for more information about the two forms of vitamin D and dosing.

(See separate reviews of Calcium and Vitamin K, which are also used in bone health).

What It Does:
Bone and fractures
Vitamin D regulates the amount of calcium and phosphorus in the body, partly by controlling their levels of absorption. Vitamin D treats and prevents rickets in children and osteomalacia (bone softening) in adults.

In children:
Given to breast-fed infants, vitamin D may help increase bone density.

In girls ages 9 to 13, regular supplementation with calcium and vitamin D has been shown to significantly increase bone density and bone strength (measured in arms and legs) compared to placebo (Greene, Osteoporosis Int 2011). Similarly, in girls ages 10 to 17, supplementation with vitamin D for one year significantly improved bone mineral density in their hips. This effect was not seen among boys of the same age (Al-Shaar, Bone 2013). It is notable, however, that 83% of the girls and 80% of the boys in this study in Lebanon were deficient in vitamin D (below 20 ng/mL) to start. In fact, 34% of the girls started with levels below 10 ng/mL. Two different doses of vitamin D3 were used in the study, a low dose (1,400 IU) or a high dose (14,000 IU), each given weekly. Interestingly, greater improvements were seen with the lower dose, although the differences were not statistically significant.

In adults:
Taken with calcium, vitamin D can help decrease post-menopausal bone loss and prevent osteoporosis (loss of bone density), as well as improve tooth retention in the elderly. However, if a person's blood level of vitamin D is already above 20 ng/mL, taking a vitamin D supplement provides no further bone benefit. This was demonstrated in a placebo-controlled study of a group of white, postmenopausal women in New York with an average vitamin D level above 20 ng/mL (but below 30 ng/mL). Taking 4,000 IU of vitamin D3 daily for 6 months did not reduce bone loss in these women (based on measurements of bone turnover markers which occur in the blood) (Aloia, J Clin Endocrin Metab 2013). In the same study, some of the women were given high-dose calcium supplementation (1,200 mg from calcium carbonate, as 600 mg twice-a-day). Those who received the calcium showed signs of reduced bone loss during the study -- regardless of whether or not they received the vitamin D supplement. This benefit is likely due to the fact that the women, on average, were not getting the recommended daily intake of calcium before supplementation (their average intake was 900 mg, while the recommended daily intake for women their age is 1,200 mg). It is possible that a lower dose of calcium would also have been beneficial, as well as more safe: Too much calcium from supplements has been associated with a higher risk of kidney stones and stroke (see Calcium Review -- Concerns and Cautions).

Another placebo-controlled study in post-menopausal women compared the effectiveness of 800 IU of vitamin D3 daily (400 IU twice a day) to the same daily dose plus an additional 20,000 IU twice a week. Both groups also received 1,000 mg of calcium daily (500 mg twice a day from calcium carbonate). After one year, bone mineral density was unchanged or slightly improved in both groups. Markers of bone turnover (bone loss) in blood serum were also reduced in both groups, but the higher dose was actually less efficient at reducing bone turnover, contrary to what the researchers had expected (Grimnes, Osteoporos Int 2012).

Similarly, a study of postmenopausal women in Wisconsin found no beneficial effect on bone mineral density from giving vitamin D at low-dose (800 IU daily) or high-dose (800 IU daily plus 50,000 IU twice monthly) for 1 year, compared to placebo. There was also no beneficial effect on muscle function, muscle mass, or falls, and only a small effect on calcium absorption. Women in the study started with a median vitamin D blood level of 21 ng/mL and, during the study, averaged 19, 28, and 56 ng/mL, respectively, in the placebo, low-, and high-dose groups. The women in this study had adequate calcium intake. The researchers concluded that the findings did not support "experts' recommendations" to maintain levels of 30 ng/mL or higher in postmenopausal women, but did support the Institute of Medicine's recommended level of at least 20 ng/mL (Hansen, JAMA 2015).


Although not all studies have shown a benefit of vitamin D supplementation in reducing fractures, a review of several studies concluded that supplementation with 800 IU or more of vitamin D was "somewhat favorable" in the prevention of hip fracture and any nonvertebral fracture in people 65 years of age or older.39 Most notably, it found a 30% reduction in hip fracture among people taking 792 to 2,000 IU of vitamin D per day compared those taking no vitamin D or small amounts (up to 360 IU per day). The review also suggested that vitamin D blood levels above 24 ng/mL are most beneficial for reducing the risk of both hip and nonvertebral fractures, and frequent dosing of vitamin D (such as daily or weekly) is more beneficial than annual dosing. Similarly, a large study of men aged 70 to 97 years in Sydney, Australia found that those with vitamin D levels between 24 and 29 ng/mL were least likely to suffer bone fractures. In comparison to this group, men with lower levels (at or below 14.4 ng/mL) and higher levels (above 29.2 ng/mL) were, respectively, 3.5 and 2.7 times as likely to experience a fracture — suggesting a potential risk from too little, as well as too much, vitamin D in the body (Bleicher, J Bone and Min Res 2014).

Vitamin D may reduce aging of bones. Compared to bone samples from the hips of people with vitamin D blood levels of 20 ng/mL or higher, bone from those with levels below 20 ng/mL (i.e., deficient in vitamin D) were found to be more brittle (over-mineralized) on the inside while thicker and under-mineralized on the outside. When physically tested, bone from vitamin D deficient people was 22% more likely to crack and the cracks were longer compared to bone from people not deficient in vitamin D. The researchers believe that osteoclast cells, which normally keep bone healthy, cannot get through the thick, under-mineralized outer layer of bone formed in vitamin D-deficient people and, as a result, areas of bone under this layer continue to age and over-mineralize even as the overall bone mineral content progressively decreases (Busse, Sci Transl Med 2013).

Calcium and vitamin D has been shown to significantly increase bone density and bone strength (measured in arms and legs) compared to placebo (Greene, Osteoporosis Int 2011).

Muscle, balance, and falls
In older adults:
Vitamin D may improve balance and reduce the risk of falls in older adults (USPSTF 2012). A review of 13 studies found that vitamin D supplements (800 to 1,000 IU daily) may improve balance and muscle strength, but not gait, among older adults.30

The benefits of taking vitamin D, however, may depend on whether or not a person has insufficient levels to start. Too much vitamin D may even have negative effects.

One of the best studies of vitamin D and falls focused on women with insufficient levels of vitamin D (blood levels less than 20 ng/mL) — they also did not take vitamin D supplements and were getting only about 120 IU daily of vitamin D from their diets. They were divided into groups given 400 IU, 800 IU, 1,600 IU, 3,200 IU, 4,000 IU, or 4,800 IU of vitamin D3 or a placebo. Over the course of one year, 58% of those given the placebo had fallen, but those given 1,600 to 3,200 IU of vitamin D3 had the lowest rate of falls — just 30%. Those given lower or higher doses did not fall significantly less than the placebo group. Women ending with blood levels of 32-38 ng/mL had the lowest rate falls (21%), while the highest rate of falls (72%) was among those with levels of 38 to 46 ng/mL. In short, those who received enough vitamin D to correct insufficiencies but remained under 40 ng/mL fared best (Smith, J Steroid Biochem Mol Biol 2017). The researchers suggested that the current upper limit on vitamin D intake of 4,000 IU daily should be lowered to 2,000 IU to reduce the risk of falls.

A small study of women aged 65 years and older with somewhat limited mobility found that those given a capsule of 4,000 IU of vitamin D3 daily after breakfast for 4 months experienced a 10% increase in muscle fiber size (measured at the thigh) compared to those given placebo (Ceglia, J Clin Endocrin Metab 2013). The supplemented group also experienced a 30% increase in vitamin D receptors in muscle cells, suggesting an effect on muscle metabolism and/or function. There was no effect, however, on physical functioning (balance, walking, rising) or knee extension power — although the study did not involve increased exercise. The women chosen for the study had moderately low vitamin D levels (mean of 18.5 ng/mL) which rose in the supplemented group to 32 ng/mL. (Note: 4,000 IU per day is a large dose at the upper tolerable intake limit, however, absorption was probably somewhat reduced as the vitamin was taken after breakfast rather than with a larger meal). 

A 9-month study in younger postmenopausal Brazilian women (ages 50 to 65) known to be deficient in vitamin D (averaging 15 ng/mL) and with a history of falls, found that a daily dose of 1,000 IU (given as liquid drops) increased the average level to 27.5 ng/mL and was associated with a 25.3% increase in muscle strength of the lower limbs, as demonstrated by chair rising test, but no increase in handgrip strength. Although there was no exercise component of the study, women receiving the vitamin D maintained lean mass (muscle) while women in the placebo group lost lean mass (Cangussu, Osteoporos Int 2015). It was separately reported that the rate of falls during the study was 46% higher for those receiving placebo rather than vitamin D, and the researchers calculated that, after adjusting for variables, the risk of a fall was actually 90% greater in the placebo group and the risk of recurrent falls was 180% greater (Cangussu, N Am Menopause Soc Meeting Abstract 2015, p. 67).

In contrast, a study in women aged 70 and older who were at-risk for bone fracture showed an increase in falls and fractures among those given an extremely high, single, annual dose (500,000 IU) of vitamin D3.10 This unexpected finding may have resulted from unusual effects of the extreme dose.11
A higher rate of falls with higher-dose vitamin D3 was also found in a study of community-dwelling men and women 70 years of age and older with a prior fall -- 58% of whom were vitamin D deficient (i.e., blood levels under 20 ng/mL)(Bischoff-Ferrari, 2016). The study compared a monthly dose of 24,000 IU of vitamin D (equivalent to 800 IU per day) to two higher doses: 60,000 IU or 24,000 IU with 300 mcg of calcifediol — a vitamin D metabolite which is 2 to 3 times more potent than vitamin D3 (Jetter, Bone 2014). Although the higher-doses raised vitamin D levels more than the lower dose, they had no benefit on lower extremity function and were each associated with an increased risk of falls over the course of a year (about 66% fell) compared with the lower dose (47.9% fell). Seniors who were not deficient in vitamin D but were given 60,000 IU per month experienced the most falls, and people whose levels reached 44.7 - 98.9 ng/mL had nearly twice as many falls as those whose levels reached 21.3 to 30.3 ng/mL.

Too high a dose of vitamin D may actually weaken leg muscles, as shown in a one-year study of overweight and obese women (with a mean vitamin D blood levels of 21.4 ng/mL) given 2,000 IU of vitamin D3 per day or placebo in conjunction with a reduced calorie diet and moderate to vigorous aerobic activity. Over the course of the year, leg strength significantly decreased in the vitamin D group (-2.5 pounds decrease in lifting weight) while it increased slightly in the placebo group (+1.8 pounds). There were no significant differences between the groups in changes in lean body mass or bone mineral density of the spine and femoral neck (Mason, JAGS 2016). The same study found no benefit on weight loss between the groups, as reported earlier (see "Weight loss control" below). Mean vitamin D levels in the treated group rose by 13.6 ng/mL to 35 ng/mL while it fell in the untreated group b 1.3 ng/mL to 20.1 ng/mL -- which is still above the cut-off for insufficiency (under 20 ng/mL).

In a study among homebound older adults, more than half of whom had insufficient (< 20 ng/mL) blood levels of vitamin D and had reported having fallen in the previous year, a monthly dose of 100,000 IU vitamin D3 taken for 5 months increased vitamin D blood levels to sufficient levels in all but person, and reduced the number of falls over the 5 months by approximately half, compared to placebo. One weakness of the study, however, is that the researchers knew who received the vitamin D3 and who received a placebo (Houston, J Am Geriatrics Soc 2015).

A study of women aged 70 to 80 in Finland who generally had sufficient vitamin D levels (averaging 25 ng/mL), showed that taking vitamin D3 (800 IU daily) for 2 years did not reduce falls, injuries from falls, or physical functioning. In fact, compared to those given placebo, the women who received vitamin D actually showed a decline in a "get up and go" test. Average blood levels of vitamin D rose to 37 ng/mL among those receiving vitamin D. In the study, some of the women were enrolled in physical training classes once or twice week and performed exercises at home (5 to 15 minutes) on the other days. Compared to women who did not train, the exercisers experienced less than half the number of injurious falls and injured fallers, although there was no decrease in the number of falls. The exercisers also showed improved muscle strength, balance and mobility, although exercisers treated with vitamin D showed smaller benefits than exercisers receiving placebo. Vitamin D did have a small effect on reducing bone loss in the hip and increasing bone density in the lower leg, but this did not translate into other benefits (Uusi-Rasi, JAMA Intern Med 2015).

The bottom line from these studies appears to be that vitamin D may help with balance and reduce falls in women with insufficient levels of vitamin D (below 20 ng/mL), but may do little or have negative effects in women with already sufficient levels. Not surprisingly, exercise can be extremely effective in reducing the risk of injury from falls.

In younger adults:
A review of seven clinical trials (from 2010 to 2013) in healthy adults aged 18 to 40 concluded that vitamin D supplementation increased upper and lower limb strength. It is important to note that the vast majority of subjects in these studies were deficient in vitamin D (average blood level was only 12.3 ng/mL), many of whom were in India, where deficiency is more common than in the U.S. High doses (2,000 IU per day to 60,000 IU per week) were used in the studies, which lasted 4 weeks to 6 months. It is not clear whether these results are relevant to a population with adequate levels of vitamin D. As noted in the review, vitamin D receptors are found on skeletal muscle and these receptors are involved in protein synthesis within the muscle, possibly explaining these findings (and those for older individuals -- discussed above) (Tomlinson, J Sci and Med in Sport 2015).

Two small studies of U.S. professional football players found associations between lower levels of vitamin D and injuries. A study of players on the Pittsburgh Steelers found that the mean vitamin D level among players who suffered a muscle injury was 19.9 ng/mL, while players with no muscle injury had a mean level of 24.7 ng/mL (Shindle, AOSSM 2011 abstract p. 56). A study of players on the New York Giants found vitamin D levels significantly lower in those with at least one bone fracture when compared with levels in those with no fractures after accounting for the number of seasons played. In addition, players who were released during the preseason because of either injury or poor performance had significantly lower vitamin D levels (62% were below 20 ng/mL) than did players who played in the regular season (11% were below 20 ng/mL) (Maroon, Am J Sports Med 2015). (The team names were not disclosed in the studies, but were identified in a Wall Street Journal article).

Statin drugs and vitamin D
If you use a statin medication for cholesterol-lowering, it may very helpful to maintain sufficient blood levels of vitamin D for the following reasons:

Statins may work better when vitamin D is adequate:
A 6-month, placebo-controlled study in China among people with high cholesterol and treated with statin drugs found that taking 2,000 IU of vitamin D3 tablets significantly improved cholesterol levels. Approximately half the people in the study began with vitamin D blood levels below 20 ng/mL (i.e., vitamin D deficient) and about another quarter had levels between 20 and 30 ng/mL. Mean vitamin D blood levels increased by 17.1 ng/mL in the treated group and by 2.4 ng/mL in the placebo group (due to increased sun exposure because the study ended in June). Compared to the placebo group, which experienced slight improvements in cholesterol levels, total cholesterol levels in the treated group fell by an additional 22.1 ng/mL, triglycerides fell by 28.2 mg/dL, LDL ("bad") cholesterol fell by 20.2 mg/dL, and HDL ("good") cholesterol increased by 8.2 mg/dL. Improvements were greater when excluding those who began the study with vitamin D levels of 30 ng/mL or higher (no analysis was reported of just those who had been vitamin D deficient). The researchers noted that these results with vitamin D may be limited to statin-treated patients (Qin, Clin Nutr 2015).

Statin-related muscle pain less likely with when vitamin D is adequate:
The risk of developing muscle pain (myalgia) and inflammation (myositis) while taking cholesterol-lowering statin drugs appears to be greater when people have lower levels of vitamin D (and keep in mind that severe vitamin D deficiency itself -- regardless of statin use -- can cause bone pain and muscle weakness). A study found that, among statin users, the average vitamin D level among those without myalgia was 34.9 ng/mL, while the average among those with myalgia was 28.4 ng/mL (Michalska-Kasiczak, Int J Cardiol 2015). A small study of people who suffered muscle pain while on statins and had generally blood levels of vitamin D averaging 22 to 23 ng/mL evaluated the effects of giving very large weekly doses of vitamin D2, ranging from 50,000 to 100,000 IU, with a goal of boosting vitamin D levels to 50 to 80 ng/mL. The researchers concluded that 88% to 95% of patients were able to tolerate statins without muscle pain at various time points in the study, although these percentages ignore those who had dropped out at earlier points due to renewed muscle pain. Over two years, 44 of the 146 patients (30%) experienced myalgia-myositis and stopped statin treatment, and 70% were symptom free. The study was not double-blind, lower doses were not tried, and, likely for ethical reasons, there was no control group (i.e., patients not given vitamin D but restarted on statins) (Khayznikov, N Am J Med Sci 2015). As noted in Concerns and Cautions, the dosage of vitamin D used in this study is very high and could be associated long-term safety risks. However, based on the evidence, it would seem worthwhile to make sure you have adequate vitamin D levels if taking a statin.

Statin-related decline in exercise performance is blunted when vitamin D is adequate:
While statins can lessen improvements in cardiorespiratory fitness that normally occur with exercise as well as reduce the content of mitochondria (i.e., the "energy powerhouses") in muscle cells, vitamin D adequacy may lessen these negative effects. A study in India among 28 people with type 2 diabetes who were vitamin D deficient (averaging about 10 ng/mL) found that, after 12 weeks of performing moderate aerobic exercise, those given simvastatin (40 mg daily) had an 8.4% decrease in cardiovascular fitness, but if also given vitamin D (60,000 IU weekly — which is a very high dose), the decrease was only 0.6%. Skeletal muscle mitochondrial content decreased 3.6% with simvastatin but improved 12.1% if vitamin D was also given. Vitamin D alone, without simvastatin, increased cardiovascular fitness and mitochondrial content by 7.1% and 16.7%, respectively (Singla, J Diabetes 2017).


More vitamin D is needed to raise blood levels when taking a statin:
A review of clinical trials in which vitamin D was given to people aged 60 and over with low vitamin D levels found that statin users had a 21.4% smaller increase in vitamin D blood levels than people not using statins (Bischoff-Ferrari, JAGS 2017). It would seem advisable to use a slightly higher than normal dose of vitamin D if you are taking a statin.

Rheumatoid arthritis
Low levels of vitamin D are also associated with a higher risk in women of developing rheumatoid arthritis. A study in China, for example, found the mean level of serum vitamin D in men and women with rheumatoid arthritis to be 17.2 ng/mL, while it was 23.2 ng/mL in a matched control group of healthy individuals. Among the patients with arthritis, lower vitamin D levels were associated with higher rates of swollen joint, tender joint, joint pain, and morning stiffness, as well as osteopenia and osteoporosis (Hong Rheumatology 2014).

Osteoarthritis (worn joints)
Giving vitamin D3 to people with painful osteoarthritis of the knee was not found to improve symptoms nor slow progression of the disease more than giving a placebo, according to a two-year study in Boston (McAlindon, JAMA 2013). In fact, throughout the study, those given vitamin D were more likely to report using non-steroidal anti-inflammatory drugs (e.g., ibuprofen) than patients given placebo. However, most patients who participated in the study were not deficient in vitamin D to begin with -- the average starting blood level of 22.7 ng/mL. Vitamin D was given at an initial dose of 2,000 IU daily and then adjusted, primarily upward, to achieve levels over 36 ng/mL. Only the subset of people who began the study deficient in vitamin D (levels below 15 ng/mL) experienced improvement taking vitamin D, although this improvement could not be considered statistically significant due to the small size of this group.

Similarly, a large three-year study among people aged 50 years and older in the UK with knee osteoarthritis given 800 IU daily of vitamin D3 showed no benefit compared to placebo with regard to progressive narrowing of the joint space, mobility, function, or pain. The average starting blood level of vitamin D was just slightly above 20 ng/mL, with half the individuals under that amount and, therefore, deficient in vitamin D. However, unlike the study above, further analysis did not show better results for those who started the study deficient in vitamin D compared to those who were not (Arden, Osteoarth Cartilge 2016).

A two-year study in Australia found that knee joint pain decreased by 36% in a group treated with vitamin D3 (50,000 IU per month: equal to 1,667 IU per day) but this was not found to be statistically significant because pain declined 26% among those given placebo. Both groups lost knee cartilage volume during the study but the loss was slightly less in the vitamin D group -- although not to a significant degree. Unlike the Boston study above, many patients in this study were deficient in vitamin D, with a mean level of 17.5 ng/mL, which, by the end of the study, was over 24 ng/mL in 79% of those treated with vitamin D and 43% of those receiving placebo. Although not an original end-point of the study, there was a statistically significant improvement in joint function for the vitamin D group compared to placebo. Interestingly, while improvements plateaued in the placebo group after 1 year, symptoms continued to improve in the vitamin D group through the second year (Jin, JAMA, 2016).

These studies suggest that vitamin D supplementation does not benefit osteoarthritis of the knee in people not deficient in vitamin D, while the evidence is mixed on whether it may help those who are deficient in vitamin D.

Cardiovascular disease, blood pressure, and cholesterol
Several studies have shown increased risk of cardiovascular disease associated with lower levels of vitamin D. Research has found that men with low levels of vitamin D in the blood (15 ng/mL and lower) are at increased risk for heart attack compared to those with levels at 30 ng/mL and higher, even after adjusting for other risk factors and physical activity. Similarly, in a study lasting about 6 years, adults with vitamin D levels below 30 ng/ml were more likely like to suffer from hypertension, coronary artery disease, cardiomyopathy, and diabetes than those with higher levels.32 In fact, after adjusting for other factors, the risk of death from all causes was 164% higher among those with the lower levels of vitamin D. The researchers note that 71% of people in the study (involving over 10,000 people in Kansas) had serum vitamin D levels below 30 ng/mL — the mean was 24.1 ng/mL. Among those with levels below 30 ng/mL, the risk of death was reduced if a vitamin D supplement was being taken; however, there was no such additional advantage with supplementation for those with levels already above 30 ng/mL. The researchers did not analyze the results by further subgroups of vitamin D level. A study which followed 230,000 men and women (average age 48) in the southwest U.S. for 5 years applied different vitamin D level subgroupings and found that the risk of cardiovascular disease was 35% higher for those with vitamin D levels below 15 ng/mL (9% of the studied population) compared to those with higher levels (Muhlestein, Circulation 2015). Although the apparent benefit of avoiding vitamin D deficiency appears dramatic, there is potential downside from much higher levels (see How Much Do You Need and "How Much is Too Much?" for more about mortality rates and vitamin D).

An analysis of two large studies showed that men who consumed 600 IU or more per day of vitamin D from foods and supplements were 16% less likely to have cardiovascular disease and stroke over a period of approximately 20 years compared to men consuming less than 100 IU per day. The same association was not seen among women; the reason for this is unclear but one possible explanation given is that women may need higher intake of vitamin D because they tend to have a higher percentage of body fat than men and vitamin D is fat soluble. In addition, vitamin D intake during the study period, which ended in 2006, may have been too low to produce meaningful differences.21 A large trial giving 2,000 IU per day as a supplement is underway and may yield additional insights (principal investigator is J.E. Manson).

A study in the UK in people with chronic heart failure (less than half the normal ventricular output) gave patients high-dose (4,000 IU) vitamin D3 or placebo daily for 1 year, with the primary goal of increasing walking distance in a 6-minute test. All of the patients started the study with vitamin D levels below 20 ng/mL. Among those given vitamin D, blood levels of vitamin D generally rose to about 50 ng/mL, however, there was no increase in walking distance -- which actually decreased by 4%, while it increased by 4% among those given placebo. Those taking vitamin D did, however, experience a modest but statistically greater improvement in heart output (left ventricular ejection fraction increased from 25.6% at baseline to 33.3%, while, in the placebo group, it increased from 26.5% at baseline to only 27.9%) (Witte, Am Coll Cardiol Sci Session 2016 (not online); Related new release). [ConsumerLab.com Comment: The high dose given in this study caused patients to achieve unusually high vitamin D blood levels -- levels associated with increased falls in other studies, possibly explaining the reduction in walking distance despite improved heart output. A lower but still higher than normal dose (e.g., 2,000 IU) could have achieved vitamin D sufficiency and may have improved heart output as well as improved walking distance.]

Low levels of vitamin D are associated with elevated blood pressure. However, studies have, at best, only shown a modest reduction in blood pressure when vitamin D is given. A comprehensive review of 46 trials concluded that vitamin D is ineffective for lowering blood pressure, regardless of starting levels of vitamin D in the blood, and should not be used as antihypertensive agent -- although most patients with hypertension in the analyzed studies were also being treated with antihypertensive medication, possibly obscuring an effect of vitamin D (Beveridge, JAMA Intern Med 2015). One trial which found no effect was conducted among adults age 70 and older with systolic hypertension. The participants, most of whom were also taking anti-hypertension medication, were given 100,000 IU of vitamin D3 every three months (equaling 1,100 IU per day) for one year, raising the mean vitamin D blood level from 18 ng/mL to 28 ng/mL. Vitamin D supplementation failed to improve hypertension or other measures of cardiovascular health, including cholesterol levels (Witham, JAMA 2013). However, another placebo-controlled study using a dose of 2,000 IU of vitamin D3 daily for 6 months found that those receiving vitamin D supplementation experienced reductions in systolic and diastolic blood pressures of, respectively, 6.2 mm Hg and 4.2 mm Hg compared to those not receiving vitamin D. People in the study were all taking nifedipine (a calcium channel blocker). Among those receiving vitamin D, mean vitamin D blood levels rose from 19.4 ng/mL to 34.1 ng/mL (Chen, Atherosclerosis 2014).

A 12-week study in Iran of overweight and obese premenopausal women found that daily supplementation for 12 weeks with 1,000 IU vitamin D3 increased HDL ("good") cholesterol by 7%. However, total cholesterol increased 1.7% and there was also a 4% increase in LDL ("bad") cholesterol — although it contained less ApoB, suggesting less plaque-forming ability. Interestingly, body fat decreased by 9.6% (about 6 lbs), although total body weight was unchanged.31 A larger and longer (2 year) study in the U.S. found that postmenopausal women given 400 IU of vitamin D3 and 1,000 mg of calcium (from calcium carbonate), taken in two divided doses daily, experienced a 4.5 mg/dL decrease in LDL cholesterol compared to those who received a placebo. Vitamin D blood levels rose to a mean of 24.3 ng/mL among the supplemented women compared to 18.2 ng/mL in the placebo group. Although there was no statistically significant effect of taking the supplement on total cholesterol, HDL, or triglycerides, the researchers did find that women with higher blood levels of vitamin D tended to have higher levels of HDL and lower levels of both triglycerides and LDL (Schnatz, Menopause 2014).

A small study of obese adolescents given a monthly dose of 100,000 IU of vitamin D3 for 3 months (averaging 3,333 IU per day) showed no improvement in arterial function and insulin and glucose levels, and increases of 32% and 9%, respectively, in triglycerides and total cholesterol. A weakness of the study was that few participants had been deficient in vitamin D (below 20 ng/mL), with the average starting level of 22 ng/mL, which increased to 35 ng/mL (Javed, Pediatric Obesity 2015).

Diabetes, insulin resistance and glucose control
Vitamin D appears to reduce the risk of insulin resistance in obese individuals. Obesity itself is a major risk factor for insulin resistance, but too little vitamin D may increase the risk. A study found that obese individuals with vitamin D blood levels below 20 ng/mL were 12 times more likely to be insulin resistant than obese individuals with sufficient levels of vitamin D.41 The researchers suggest that insulin resistance in obese individuals may be reduced by making improvements in vitamin D levels. More specifically, a study of overweight and obese women who were not diabetic found that vitamin D blood levels of at least 26 ng/mL appear to be needed for normal glucose metabolism in both black and white women (Sorkin, JN 2014). In fact, women with this amount of vitamin D had lower body fat, blood glucose, insulin and triglyceride levels than women with lower levels of vitamin D. It is not clear whether any further benefit is gained with respect to these measures when blood levels of vitamin D higher than 26 ng/mL.

A study among 81 healthy men and women in Japan, most of whom had low or deficient blood levels of vitamin D (average blood level 13 ng/mL) found that, compared to placebo, 420 IU of vitamin D3 taken daily for one year increased average blood levels of vitamin D (to an average of 24 ng/mL; Note: this is a large increase for a moderate dose, partly due the fact that participants were not overweight), and significantly decreased fasting blood glucose (from an average of 88.3 mg/dL to 85.3 mg/dL) and improved insulin resistance values (as measured by HOMA-IR ) from 1.17 to 0.84 (Sun, Nutr Res 2016). Although all results stayed well within the normal range, the results suggest that in healthy people, maintaining adequate blood levels of vitamin D may have a beneficial effect on blood sugar and insulin levels.

Having insulin resistance increases the risk of type 2 diabetes. So it is not surprising that a review of studies found that daily vitamin D intake over 500 IU decreased the risk of type 2 diabetes by 13% compared with intake of less than 200 IU. Similarly, individuals with vitamin D levels over 25 ng/mL had a 43% lower risk of developing type 2 diabetes compared to those with levels under 14 ng/mL. However, vitamin D supplementation has not been shown to affect glucose tolerance among people with established type 2 diabetes.23 (Also see "Depression" below for more about type 2 diabetes and vitamin D.)

Supplementation with a combination vitamin D and calcium may improve blood sugar control in pregnant women with gestational diabetes. In a six-week study of 56 women with gestational diabetes (at 24 to 28 weeks gestation), those who received 1,000 mg calcium per day, plus 50,000 IU of vitamin D3 at the beginning of the study and another 50,000 IU at week 3, had significantly lower fasting blood glucose levels compared to those receiving placebo (respectively, a 0.89 mmol/l reduction versus a 0.26 mmol/l increase), lower serum insulin levels (-13.55 vs. +9.17 pmol/l), and a significant increase in insulin sensitivity (+0.02 vs -0.002 ) compared to those receiving a placebo (Asemi, Diabetologia 2014).

Higher serum levels of vitamin D — up to a point -- have been associated with a lower risk of developing type 1 diabetes (i.e., requiring insulin). In a study of two thousand people on active duty in the military, those with levels between 24 and 31 ng/mL had the lowest risk of being diagnosed with type 1 diabetes. Compared to this group, the risk of diabetes was more than 2.5 times as great among those with levels between 17 and 24 ng/mL, and the risk was more than 3.5 times as great among those with levels below 17 ng/mL. No risk reduction was associated with levels above 31 ng/mL — in fact, the risk of diabetes was slightly higher for those with levels above 31 ng/mL than those with levels between 24 and 31 ng/mL. (Gorham, Diabetologia 2012). There is also preliminary evidence that giving vitamin D supplements to infants might decrease the risk of type 1 diabetes later in life.

A study in Denmark found that both high and low vitamin D levels are associated with a form of nerve damage called cardiovascular autonomic neuropathy (CAN) in people with type 1 and type 2 diabetes. CAN affects heart rate and blood vessel function and may cause low blood pressure on standing and exercise intolerance. Patients with CAN have a greater chance of having a heart attack and lower chance of surviving one. The findings suggest that beneficial effects of vitamin D are restricted to a specific serum range (around 20 ng/mL to 50 ng/mL) and both too low and too high levels are detrimental to the autonomic nervous system (Hansen, Diabetic Med 2016).This may help explain similar associations found between vitamin D levels and falls as well as mortality.

Non-alcoholic fatty liver disease (NAFLD):
Low levels of vitamin D have been associated with non-alcoholic fatty liver disease -- the accumulation of fat in the liver (also called hepatic steatosis) which can lead to inflammation, scarring and cirrhosis (Elaides, Aliment Pharmacol Ther 2013). A preliminary study in 40 women and men with significant liver fat accumulation and insufficient blood levels of vitamin D (averaging 11.8 ng/mL) found that with a weekly dose of 20,000 IU of vitamin D3 (equivalent to about 2,857 IU per day), liver fattiness decreased by approximately 5% after only four weeks; while vitamin levels rose to an average of about 35 ng/mL. A weakness of this study, however, is that it did not include a control group (Papaostoli, J Gastrointestin Liver Dis 2016).

Inflammation
Raising low levels of vitamin D may also reduce inflammation in the body. In a study of blood from thousands of adult Americans, levels of C-reactive protein (CRP), a marker of inflammation, decreased as vitamin D levels increased to just below 21 ng/mL28 However, there was no further benefit when vitamin D levels reached and exceeded 21 ng/mL. In fact, after adjusting for cardiovascular risk factors, it was found that CRP levels slowly but progressively increased at that point, suggesting a slight inflammatory action of vitamin D at these higher levels. The results seem to reinforce the importance of maintaining a plasma vitamin D level of at least 20 ng/mL and suggest some potential downside of higher levels of vitamin D.

Somewhat similar conclusions were drawn from a well-controlled, 1-year study of vitamin D in adults aged 60 to 84 years in Australia. Starting with vitamin D levels of about 17 ng/mL, people were given monthly dose of vitamin D of 30,000 IU (equal to 1,000 IU/day), 60,000 IU, or a placebo. At 1 year, there were no significant differences in levels of inflammatory biomarkers in the treated groups versus placebo — except for a slight increase in a pro-inflammatory marker (IL-6) in the higher-dosed group, half of whom achieved vitamin D blood levels of 30 ng/mL or higher. The researchers note that this may suggest a detrimental effect of higher vitamin D levels but this uncertain (Waterhouse, Br J Nutr 2015).

Vitamin D appears to accelerate the resolution of inflammatory responses during tuberculosis therapy.42 In a study in London, patients given very large doses of vitamin D3 (100,000 IU every 2 weeks) along with standard antibiotic therapy had less inflammation, and their infections cleared 13 days earlier on average, than patients who did not receive vitamin D. It is important to note, however, the very high prevalence of profound vitamin D deficiency in the studied population -- more than half the patients had levels of vitamin D below 8 ng/mL prior to therapy. Added vitamin D may not yield the same benefits for patients who already have sufficient levels of vitamin D.

Asthma
A review of medical studies published from 1950 to 2009 that looked at, among other variables, vitamin D intake and asthma, suggested that vitamin D deficiency may be linked to airway inflammation, decreased lung function and poor asthma control. The researchers conducting the review hypothesized that vitamin D supplementation may lead to improved asthma control, although this cannot be established as many of the studies were not specifically designed to test the effects of vitamin D supplementation on patients with asthma.15 A clinical study published in 2014 tested whether high-dose vitamin D supplementation reduced treatment failures among adults with asthma already receiving an inhaled corticosteroid (ciclesonide) and a bronchodilator (levalbuterol). Vitamin D supplementation (4,000 IU per day after an initial 100,000 IU dose) did not lead to a statistically significant reduction in initial treatment failures compared to those receiving a placebo supplement. However, during the 28-week study, the group receiving vitamin D was 20% less likely to have a treatment failure and 37% less likely to have an exacerbation of symptoms. It is possible that more significant results may have been obtained if the study did not have certain weaknesses: Half the patients started the study with vitamin D levels above 20 ng/mL and, therefore, were not vitamin D deficient and might not benefit from additional vitamin D; and, because of the very high dosage used in the study, many of these people may have achieved unusually high blood levels of vitamin D which other studies suggest may counter beneficial effects of vitamin D (Castro, JAMA 2014. Further analysis of this group found no benefit regarding colds -- see Denlinger study, below). A small pilot study (not placebo-controlled) tested a lower dose (a daily capsule of 2,000 IU of vitamin D3) for 12 weeks in asthmatic people age 65 and older in Philadelphia. Prior to initiation of therapy, it found that mean vitamin D levels in the blood were significantly lower (19.0 ng/mL) in those with uncontrolled asthma compared to those with well-controlled symptoms (25.7 ng/mL). Self-reported symptoms of asthma decreased significantly after 12 weeks of vitamin D treatment only in patients who had uncontrolled asthma, although clinical measurements of airflow remained unchanged. The researchers note that vitamin D receptors are present in the smooth muscle of the bronchi and vitamin D has been shown to play a role in modulating the immune system (Columbo, Allergy, Asthma, & Clin Immun 2014).

A study in Japan among schoolchildren with asthma found that giving them each 800 IU of vitamin D daily for two months led to significantly greater improvements in asthma control than did giving a placebo. This improvement remained significant even four months after discontinuing vitamin D, at which point 34% of those who had received placebo had difficulty breathing compared to only 15% of those who had received vitamin D. Interestingly, the children in both groups had had relatively high levels of vitamin D (around 30 ng/mL) before the trial began and few were vitamin D deficient (Tachimoto, Allergy 2016).

A review in 2016 of seven clinical trials (ranging in length from 4 months to one year -- including the Castro and Tachimoto studies noted above) investigating the effects of vitamin D supplementation in children or adults with asthma (most of whom had mild to moderate asthma and used their regular asthma medications as needed) found that oral vitamin D supplementation (average daily dose 900 IU vitamin D3, although some participants received additional, larger doses in some trials) reduced the average number of attacks per year requiring treatment with oral steroid medication from 0.44 to 0.22, and reduced the risk of hospitalization from asthma attacks from 6% to about 3%. However, measures of lung function (such as forced expiratory volume, or FEV1) were not improved (Martineau, Cochrane Database Syst Rev 2016). Due to lack of data, the researchers were not able to assess whether the improvements would be limited to those who were deficient in vitamin D before supplementation, or whether those with more severe asthma would benefit.

In summary, moderate doses of vitamin D may improve symptoms of asthma in children as well as in adults with uncontrolled asthma.


COPD (Chronic obstructive pulmonary disease)
A placebo-controlled study of 240 people with COPD found that taking vitamin D3 (120,000 IU orally every 2 months — equal to 2,000 IU per day) significantly reduced the risk of having moderate or severe exacerbations among those who began the study deficient in vitamin D (blood levels below 20 ng/mL). This benefit was not found for those who began the study with sufficient levels of vitamin D. Vitamin D did not reduce the risk of upper respiratory infection among any group. (Martineau, Lancet Resp Med 2014). Somewhat similarly, a study found that vitamin D supplementation (100,000 IU every 4 weeks) significantly reduced exacerbations of COPD but only among patients starting with vitamin D levels less than 10 ng/mL (Lehouck, Ann Intern Med 2012).

Allergy
Higher serum vitamin D levels are associated with a reduced risk of allergy in children and adolescents. A review of data from a nationwide study of over 6,000 individuals showed that allergic sensitization was more common in those with serum vitamin D of less than 15 ng/mL compared to those with 30 ng/mL or greater for 11 out of 17 allergens. Results were adjusted for potentially confounding factors like time spent on indoor activities. The strongest associations were for allergy to oak (5 times the risk), peanut (2.4 times the risk), and ragweed (1.8 times the risk). There was also increased risk of allergy to dog, cockroach, mite, shrimp, ryegrass, Bermuda grass, birch and thistle. In adults, there was no consistent association between allergy and vitamin D levels.19

Giving vitamin D daily to infants (as well as to their mothers while
pregnant) reduces infants' risk of allergic sensitivity to dust mites and reduces visits to the doctor for asthma during the infancy. This was shown in a study in New Zealand in which pregnant women were given 1,000 IU or 2,000 IU of vitamin D during the last 3 months of pregnancy and their newborn infants were then given, respectively, 400 IU or 800 IU for 6 months. Another group of mothers and infants received placebo. During the first 18 months of life, 11% of infants in the placebo group saw a doctor for asthma, compared to 0% who received the lower dose of vitamin D and 4% who received the higher dose. Virtually all of the infants were breasfed at birth, although 47% began infant formula prior to age six months. The researchers noted that other studies have shown that sensitization to dust mites is associated with increased risk of childhood asthma (Grant, Allergy 2016).

Fibromyalgia
Preliminary studies suggest improvements in symptoms of fibromyalgia with vitamin D supplementation. Fibromyalgia is a common syndrome in which a person has long-term, body-wide pain and tenderness in the joints, muscles, tendons, and other soft tissues. Recently, a randomized controlled study found that increasing vitamin D blood levels from a mean of 19 ng/mL to about 50 ng/mL was associated with a modest decrease in fibromyalgia pain (a 20 point decrease on a 100 point scale). The study involved 30 adults (mostly women) in Austria with fibromyalgia. Most of the participants started the study with vitamin D levels below 24 ng/mL and were given 2,400 IU of vitamin D3 daily, while those starting with levels between 24 ng/mL and 32 ng/mL were given 1,200 IU daily. Treatment continued for 20 weeks or until vitamin D levels reached 48 ng/mL (levels in several patients went as high as 55 to 93 ng/mL). Twenty-four weeks after supplementation ended, pain returned to the original level in the group (Wepner, Pain 2013).

Headache
A study among 2,601 middle-aged men in Finland found those who had the lowest blood levels of vitamin D (under 12 ng/mL or below) were twice as likely to report frequent headaches than men with higher blood levels. About 15% of men with the lowest levels (less than 12 ng/mL) had headaches at least weekly, while the percentage was only 8% among men with levels of 12 to 16 ng/mL, 16 to 22 ng/mL, or above 22 ng/mL (Virtanen, Scientific Reports 2016). The researchers noted that vitamin D deficiency has also been associated with chronic tension-type headache, perhaps by causing musculoskeletal pain.

Lupus
A preliminary study suggests that raising low vitamin D levels with supplementation provides beneficial immunological effects in patients with systemic lupus erythematosus (SLE). Giving 100,000 IU of vitamin D3 (weekly for a month and then monthly) along with regular therapy to SLE patients with generally low vitamin D levels (averaging 19 ng/mL) raised vitamin D blood levels to 42 ng/mL after 6 months of therapy, during which patients experienced no flare ups and experienced an increase in regulatory T cells and decreases in memory B cells, effector T cells, and anti-DNA antibodies (Terrier, Arth Res & Ther 2012).

Arthritis
Low levels of vitamin D are also associated with a higher risk in women of developing rheumatoid arthritis.

Menstrual pain and Premenstrual Syndrome (PMS)
A small study of women with primary dysmenorrhea (painful menstrual cramping) and a mean vitamin D blood level of 27 ng/mL found that giving a single high dose (300,000 IU) of vitamin D3 reduced pain by 41% during the next two menstrual periods. None of the women who received vitamin D needed anti-inflammatory medicine to manage menstrual pain during the two months, whereas 40% of those taking placebo used it at least once.29 A concern, however, is that high dose vitamin D has been shown to increase the risk of falls and fractures — at least in the elderly (as noted above) and the dose given works out to 5,000 IU vitamin D per day, more than the tolerable upper intake level of 4,000 IU per day (see Concerns and Cautions).

A study among extremely vitamin D deficient (< 10 ng/mL) adolescent and young women (ages 15 — 21) with self-reported severe or extremely severe emotional and cognitive symptoms associated with premenstrual syndrome found that high-dose supplementation (an initial dose of 200,000 IU followed by 25,000 I.U. every two weeks ) with liquid vitamin D3 (Dibase®, Abiogen Pharma, Italy) for four months significantly reduced these symptoms: Mean scores of "irritability" decreased from 130 to 70, "crying easily" decreased from 41 to 30, sadness decreased from "51 to 31" and "disturbed relationships" decreased from 150 to 70 compared to the beginning of treatment. Those who took a placebo had a significant reduction only in "irritability" (from 128 to 119). (Tartagni, J Pediatr Adolesc Gynecol 2015). It should be noted that the dosing may have been unnecessarily high as blood levels rose to 35 to 60 ng/mL.

Uterine fibroids
A study of women ages 35 to 49 found that those with vitamin D levels above 20 ng/mL were 32% less likely to have had uterine fibroids than those with lower levels. Similarly, women who reported getting at least one hour per day of sun exposure (weather permitting), were 40% less likely to have had fibroids than women reporting less sun exposure (Baird, Epidemiology 2013). The risk of fibroids appeared to continue to decrease as vitamin D levels approached 35 ng/mL. Possibly explaining these findings are laboratory studies showing that vitamin D in its active form inhibits the overproduction of tissue by uterine muscle cells -- the cause of fibroids. The study was conducted in Washington, D.C. in the late 1990s and only 10% of black women and 50% of white women had vitamin D levels above 20 ng/mL. Fibroids are the leading reason for hysterectomy in the U.S.

Pregnancy
Vitamin D levels in the blood of pregnant women are associated with infant growth. A study in the U.S. found that the birth weight and head circumference of babies rose with increasing vitamin D levels up to 15 ng/mL (Gernand, J Clin Endocrin & Metab 2012). Mothers with levels of 15 ng/mL or greater gave birth to newborns 46 grams (0.1 lb) heavier and with head circumferences 0.13 cm larger, on average, than those of mothers with vitamin D levels less than 15 ng/mL. A level of 15 ng/mL or greater in the first trimester was also associated with half the risk of an infant being small for its gestational age.

A study in India evaluated the effect of giving pregnant women large doses of vitamin D. Those with already sufficient levels (above 20 ng/mL) were given a single dose of 60,000 IU D3 at week 20 of their pregnancy (averaging about 400 IU per day over the duration of their pregnancy), and those with insufficient (10 to 20 ng/mL) or deficient (<10 ng/mL) levels were given a monthly dose of 120,000 IU twice or four times, respectively, raising the average blood level of the entire group to 32 ng/mL. In another group of women who were not given vitamin D (average vitamin D level of 18.4 ng/mL), 44% developed pre-term labor, pre-eclampsia, and/or gestational diabetes, in contrast to 20.3% of the women given vitamin D. The non-treated group also had babies with a lower average birth weight (5.28 lbs) than did those given vitamin D (5.72 lbs) (Sablok, Clin Endocrinol 2015). The researchers note that lower-dose daily preparations may have been preferable to the large monthly doses but were not available.

Respiratory infection, colds, and influenza
In healthy adults with generally sufficient vitamin D levels (averaging 29 ng/mL), monthly supplementation of high dose vitamin D3 (100,000 IU) resulted in no reduction in the number of upper respiratory infections (colds), the severity or duration of such infections, nor the number of days of missed work, compared to a similar group of people given placebo (Murdoch, JAMA 2012). Among those receiving the supplement, vitamin D levels averaged over 48 ng/mL throughout the study. The researchers commented that vitamin D supplementation may have been helpful had the population been vitamin D deficient, citing a study in which vitamin D supplementation was associated with a 50% reduction in acute respiratory infections among Mongolian schoolchildren who had an average vitamin D level below 10 ng/mL (Camargo, Pediatrics 2012).

A study in London found that periodic high doses of vitamin D increased the risk and duration of respiratory infections. The study was conducted among 194 older residents of group homes and 46 of their caregivers (average age was 67 years). Sixty-four percent of subjects began the study with blood levels below 20 ng/mL (92% were below 30 ng/mL). During the study, all residents were given 400 IU of vitamin D3 daily and more than half were given an additional 96,000 IU every two months -- for a total dose averaging 2,000 IU per day. (A subgroup of caregivers was given what also averaged to 2,000 IU per day, but as 120,000 IU every two months.) Over one year, those who received the large doses of vitamin D were 48% more likely to develop an upper respiratory infection than those who did not receive the large doses, and these infections lasted longer (7 days vs. 5 days, respectively). The researchers note that other studies have found that relatively low-dose vitamin D has been shown to offer protection against upper respiratory infection and that intermittent large doses have not. Interestingly, those receiving large doses had an average level of 34 ng/mL at the end of the study (2 months after the last large dose), while those who did not receive large doses (most of whom received just 400 IU daily) and had fewer respiratory infections ended the study with levels averaging 24 ng/mL. (Martineau, Thorax 2015).

Similarly, a placebo-controlled study in people with mild to moderate asthma found that giving high-dose vitamin D (100,000 IU initial dose and 4,000 IU daily for 28-weeks) did not decrease the risk of developing a cold. In fact, with this vitamin D supplementation (which raised the mean vitamin D level to 42 ng/mL), the risk of a developing a cold was found to be 40% higher among those who reached vitamin D blood levels of 30 ng/mL or higher, and 70% higher among those who were African-American (Denlinger, Am J Resp and Crit Care Med 2015. Also see Castro study, above, for effects on asthma control in this same group.)

In contrast the above studies in adults, a study in Sweden found vitamin D supplementation to be quite helpful. The double-blind study was conducted in adults with frequent upper respiratory infections in whom vitamin D levels tended to be low (half had levels below 20 ng/mL). Many also had immunodeficiencies. Vitamin D3 (4,000 IU) or placebo was taken daily for one year. Although benefits were not seen until after 3 months, over the full course of the year vitamin D reduced the risk of infection by 36% and the total number of respiratory tract infections by 28% relative to placebo (Bergman BMC Res Notes, 2015). An earlier analysis of the same study additionally showed that vitamin D resulted in reductions of 50% in positive bacterial cultures and 60% in antibiotic consumption (Bergman, BMJ Open 2012).

A study among older men and women (average age 81) in a long-term care facility with average vitamin D blood levels of about 23 ng/mL who, each month, received either high dose (100,000 IU) or a lower dose (which was either 12,000 IU monthly or 400 IU to 1,000 IU daily as part of standard care) found that over the course of a year, those who received high dose vitamin D3 had a 40% lower incidence of acute respiratory infections compared to those who received the low dose. However, the high dose patients were also more than twice as likely to experience a fall (although not a fracture) during the study period (Ginde, J Am Geriatr Soc 2016) — a finding in line with other research showing that high dose vitamin D may weaken legs and increase the risk of falls (See "Muscle, balance and falls" for more about this).

Researchers in Japan studied the effect of vitamin D3 supplements (1,200 IU per day from December through March) on the incidence of seasonal influenza A in school children. Influenza A infection occurred in 18.6% of children in a placebo group versus 10.8% of children who received the supplement -- a 42% reduction in risk among those taking the supplement. The reduction was more prominent among children who had not been taking other vitamin D supplements. Influenza infection was not reduced among a subgroup of asthmatic children but those who became infected were significantly less likely to have an asthmatic attack if they had received vitamin D than if they had not. Supplementation did not affect the incidence of influenza B (which is less common than influenza A and is not seasonal).14

An analysis of 25 studies of vitamin D for cold and flu (including many of the studies noted above) concluded that vitamin D supplementation protected against acute respiratory tract infection, but the patients most likely to benefit were very deficient (blood levels of vitamin D below 10 ng/mL) and receiving daily or weekly doses rather than less frequent, large doses. Giving vitamin D reduced the risk of infection by 42% in people with levels below 10 ng/mL, and by 70% if dosing was daily or weekly. For those with levels above 10 ng/mL, the risk reduction with giving vitamin D was only statistically significant when given daily or weekly, resulting in a 25% reduction in risk of infection (Martineau, BMJ 2017).

Based on the studies above, vitamin D appears to be most effective in reducing respiratory infections when patients do not already have adequate levels (20 ng/mL) of vitamin D and when vitamin D is given daily, not in extremely large periodic doses.

Adequate vitamin D levels were associated with a lower risk of pneumonia in a study of men and women ages 53 to 73 in Finland which followed them for an average of nine years ( Aregbesola, J Epid Comm Hlth 2013). Compared to adults with vitamin D levels above 20 ng/mL, the likelihood of being hospitalized with pneumonia was 40% higher among those with levels below 20 ng/mL but above 13.5 ng/mL, and 140% higher among those with levels below 13.5 ng/mL, after adjusting for other factors which might predict pneumonia. The researchers found that a low vitamin D level was almost as strong a risk factor for pneumonia as smoking.

Ear infection (Otitis media)
Among children ages 1 to 5 years with a history of recurrent ear infections, those with higher blood levels of vitamin D had a decreased risk of developing uncomplicated ear infections (acute otitis media) during a 6-month study including wintertime. However, the study found that higher vitamin D levels did not reduce the risk of complicated ear infections (e.g., ear drum rupture). In fact, rates of complicated infections were actually higher at vitamin D levels above 30 and 40 ng/mL than at lower levels, leading the researchers to speculate that these higher vitamin D levels potentially foster certain bacterial infection in the ear. The study also found that giving 1,000 IU daily for 4 months raised vitamin levels from about 26 ng/mL to 37 ng/mL, while levels fell to about 19 ng/mL in children receiving placebo (due to reduced sun exposure in winter). Although the children receiving vitamin D experienced significantly fewer episodes of uncomplicated ear infections, there was no significant reduction in complicated infections (Marchisio, Pediatr Infect Dis J 2013). It would seem best for children to follow the recommendations for vitamin D outlined in the Summary above.

Depression
Lower levels are also associated with a higher risk and severity of depression. A study in Italy, for example, showed that older women with low vitamin D levels (below 20 ng/mL) were twice as likely to develop depressive mood as those with higher levels. Older men with low levels were 60% more likely to develop depressive mood.9 Data from the same study showed that those who were severely vitamin D deficient (below 10 ng/mL) were approximately 60% more likely than those with vitamin D levels above 30 ng/mL to experience substantial cognitive decline, although there was no such association with attention level.13 In a separate study lasting 3 years, the risk of depression was found to be 21% lower among women (aged 50 to 79) who reported total daily vitamin D intake (from foods and supplements) of at least 800 IU compared to women with intake of less than 100 IU. Excluding women with evidence of depression at the beginning of the study, a 20% lower risk of depression was seen with intake of just 400 IU or more per day. However, further analyses showed no reduction in the risk of depression resulting from vitamin D supplements alone. The reductions were only associated with higher vitamin D intake from foods.24 More recently, a 6-month pilot study in the U.S. suggested that high-dose vitamin D (50,000 IU of vitamin D2 per week) significantly improved mood in women with type 2 diabetes who had serious depressive symptoms. Mean serum blood levels of vitamin D increased from 18.8 ng/mL to 37.5 ng/mL during the intervention. The study also showed a modest improvement in systolic blood pressure and a slight decrease in weight (Penckofer, Abstract from ADA Scientific Sessions 2013). Although promising, the study had no control group and a larger, controlled study is underway using vitamin D3.

 Alzheimer's disease, dementia and cognitive decline
A study which followed 1,658 older adults in the U.S. for a mean period of 5.6 years found that the risk of developing dementia increased when starting blood levels of vitamin D were below 20 ng/mL. All participants were relatively healthy at the start of the study. People who began the study with a level of 10 ng/mL up to 20 ng/mL were 53% and 69% more likely to develop dementia and Alzheimer's disease, respectively, than those with starting levels of 20 ng/mL and above; and people with levels below 10 ng/mL were 125% and 122% more likely to develop dementia and Alzheimer's disease, respectively, than those starting with levels of 20 ng/mL or above. While the study suggests that higher levels of vitamin D may be beneficial, it did not test whether raising a person's vitamin D level reduces the risk of dementia. However, as the researchers note, it clarifies that having a level above approximately 20 ng/mL is unlikely to further reduce the risk of developing dementia (Littlejohns, Neurology 2014).

Similarly, a study which followed older, ethnically diverse adults in California for a mean period of 4.8 years found that rates of decline in two areas of cognitive functioning -- episodic memory (word list learning) and executive functioning -- were greater among those starting with vitamin D levels below 20 ng/mL than those starting with levels of 20 ng/mL and above. Decline in these two areas are strongly associated with Alzheimer's dementia. Vitamin D status was not associated with rates of decline in two other cognitive areas: semantic memory (object naming and picture association) and visuospatial ability. The average starting level of vitamin D among the participants was 19.2 ng/mL (Miller, JAMA Neurol 2015)

A study in France among women 75 years of age and older found those with higher intakes of vitamin D from their diets least likely to develop Alzheimer's disease over a seven-year study period.43 Women consuming more than 3,108 IU of vitamin D per week (444 IU per day) were 77% less likely to develop Alzheimer's disease than those with lower vitamin D intake. There was, however, no association between vitamin D intake and the risk of developing other types of dementia. The study excluded women who had taken vitamin D supplements.

 These studies suggest that maintaining a vitamin D of at least 20 ng/mL may be helpful in reducing the risk of developing Alzheimer's disease.

 Parkinson's disease
A study from Finland suggested that higher vitamin D status provides protection against Parkinson's disease. People with the highest vitamin D levels (above 20 ng/mL) had a 65% lower risk of developing Parkinson disease than those with the lowest vitamin D levels (below 10 ng/mL).

Multiple sclerosis
Vitamin D has been associated with a decreased risk of developing multiple sclerosis (MS) in adulthood. There is mixed evidence as to whether vitamin D levels of pregnant mothers correlate with MS risk in their children, but one study (in Finland) found that the risk of MS as an adult was 90 percent higher in children of mothers who were significantly deficient in vitamin D (levels less than 12.02 ng/mL) compared with the children of mothers with levels between 12.02 ng/mL and 20.03 ng/mL (Munger, JAMA Neurol 2016).

Autism
 A study in the Netherlands found that children whose mothers had very low vitamin D blood levels (< 10 ng/mL) during pregnancy (measured during the fifth month of gestation) were 3.8 times as likely to have autistic traits by age six than those whose mothers had sufficient vitamin D levels (20 ng/mL). Even with levels between 10 and 19 ng/mL, there was a 75% higher risk, although this was not deemed statistically significant (Vinkhuyze, Mol Psychiatry 2016). The researchers noted that vitamin D is involved in the production of the neurotransmitter serotonin, which may play a role in certain autistic characteristics.

 Researchers in Egypt noted an association between lower blood levels of vitamin D and higher severity of autism symptoms. They then conducted a study giving children with autism spectrum disorder (ages 3 to 10) high-dose (5,000 IU ) vitamin D (as drops), (or less for children under 36 lbs), daily for 4 months. Symptoms improved, on average, from "moderate" to "mild," while there was no change among children given placebo drops. Be aware that the dose given exceeds the upper tolerable intake level (UL) for vitamin D (3,000 IU to 4,000 IU for children this age) and vitamin D levels were boosted from an average of 26.3 ng/mL to 45.9 ng/mL, which seems excessive. Lower doses were not tested. The researchers note that additional studies are needed to validate these findings ( Saad, J Child Psychol Psychi 2016). 

Executive functioning
Executive functioning refers to the set of mental skills that help you get things done, like planning and strategic thinking. Maintaining a sufficient level of vitamin D appears to be associated with better executive functioning, according to a study in Norwegian adolescents. The study found that adolescents with low vitamin D blood levels (below 20 ng/mL) scored worse on tests of executive functioning and were more likely to report attention issues than those with higher levels. It also found that giving 1,520 IU (or 38 mcg) of vitamin D3 daily for three months (which increased average vitamin D blood levels from 17.6 ng/mL to 24.8 ng/mL) improved performance on the most demanding executive functioning tasks -- although not on easier tasks (Grung, Scan J Psychol 2017). A preliminary study among Norwegian men also suggests a positive association between vitamin D blood levels of 20 ng/mL and above and better executive functioning (Hansen, Percept Motor Skills 2011).

 Weight control
A 12-month study found that taking vitamin D3 had no overall effect on weight or fat loss in overweight or obese postmenopausal women consuming a reduced calorie diet and following a program of 45 minutes of aerobic 5 days per week (Mason, Am J Clin Nutr 2014). Regardless of whether they took 2,000 IU vitamin D3 daily or a placebo, women lost an average 16 lbs. (Note: The 2,000 IU dose of vitamin D is fairly high for regular daily use and 7% of the women taking vitamin D achieved levels above 50 ng/mL, which is potentially harmful. In fact, a subsequent analysis of this study found that those who received vitamin D lost strength in their leg muscles -- see "Muscle, balance, and falls" above.) Interestingly, among the vitamin D-treated women, those who achieved blood levels greater than 32 ng/mL lost more weight than those whose levels remained below 32 ng/mL (19 lbs vs. 12 lbs) and had greater reductions in their waistlines (3.5 inches vs. 2.2 inches) and body fat. However, it may just be that vitamin D levels in the blood rose more in women who lost more fat, due to the fact that vitamin D is fat soluble and stored within fat; indeed, an earlier study by the same researchers showed that weight loss raises vitamin D levels (Mason, Am J Clin Nutr 2011).

 Frailty
A study found that older women (69 years and older) whose vitamin D levels were not between 20 and 29.9 ng/mL had a greater risk of being frail.18 Frail individuals were those experiencing at least three of the following criteria: weight loss, weakness, exhaustion, slowness, and low physical activity. The risk of frailty was increased by 47% among those with vitamin D levels below 15 ng/mL, 24% among those with levels below 20 ng/mL, and 32% among those with levels above 29.9 ng/mL. An average of 4.5 years after these measurements were made, those originally not frail but whose blood levels had been below 20 ng/mL were 21% more likely to have become frail or died. These findings correspond with the 2010 report from the Institute of Medicine (IOM) indicating that 20 ng/mL is a sufficient level for vitamin D and that levels above 30 ng/mL may be associated with certain risks.17

Cancer
While there is conflicting evidence about whether vitamin D helps reduce the overall risk of dying from cancer, studies generally show that having vitamin D serum levels above 20 ng/mL are associated with lower risk of various cancers.

A moderately decreased risk of developing colorectal cancers, specifically, has been demonstrated with higher vitamin D levels as well as with higher vitamin D intakes (Ma, J Clin Oncol 2011). An analysis of data from two large studies of health professionals found higher vitamin D levels to be associated with a much lower risk of developing a subtype of colorectal cancer in which there is extensive immune cell infiltration within the tumor — perhaps explained by vitamin D's effects on the immune system. Compared to people with the lowest vitamin D blood levels (around 19 ng/mL), those with mid-range levels (around 27.9 ng/mL) had only 33% of the risk of developing this type of tumor, and those with the highest vitamin D levels (around 37.4 ng/mL) had just 10% of the risk (Song, Gut 2015).

In seeming contrast to this, a large, multi-year study in the U.S. found that daily supplementation with vitamin D3 (1,000 IU) and/or calcium (1,200 mg) did not reduce the risk of developing new precancerous colorectal polyps (adenomas) among people who had adenomas removed in the past. There was no statistically significant difference in the occurrence of adenomas between those who were or were not given the supplements. However, the vast majority of subjects began the study with adequate blood levels of vitamin D (averaging 24 to 25 ng/mL); in fact, anyone with a level below 12 ng/mL was excluded from the study (Baron, NEJM 2015). These findings, therefore, may not apply to people with vitamin D levels which are inadequate, i.e., under 20 ng/mL.

A study of 1,666 women (average age 59) with breast cancer found that those with higher vitamin D blood levels around the time of diagnosis had the highest overall survival rates over an average 7 years of follow up. Nineteen percent of women with the lowest levels of vitamin D (under 17 ng/mL) died during the follow up period, while only about 14% died among those with higher levels. After accounting for differences in tumors and treatments, it was calculated that women with vitamin D levels of 17 to 25 ng/mL and those with more than 25 ng/mL were, respectively, 22% and 28% less likely to have died than women with the lowest levels. The reduction in risk associated with vitamin D was greatest for premenopausal women. Women with lowest blood levels of vitamin D at the time of diagnosis were more likely to have the most advanced-staged tumors (Yao, JAMA Oncol 2016).

Somewhat similarly, an analysis in 2014 of five clinical studies found that women who had the highest vitamin D blood levels at the time of breast cancer diagnosis were twice as likely to survive during the studies (which lasted 5 to 20 years) as women with the lowest vitamin D levels (Mohr, Anticancer Research 2014). Due to differences in the studies analyzed, the "low" vitamin D groups included women with less than 14 to 30 ng/mL of vitamin D while the "high" groups included those with more than 22 to 32.4 ng/mL.

While this association between vitamin D levels and mortality with breast cancer is not proven to be "cause-and-effect," there is no scientific reason to believe that breast cancer would cause a decrease in vitamin D, suggesting a likely beneficial effect of vitamin D.

This potential beneficial link between vitamin D and breast cancer was somewhat strengthened by analysis of a study which gave 2,000 IU daily to overweight or obese postmenopausal women in the hope that it would aid weight loss during dieting -- although it did not (see Mason 2014 study in "Weight control" above). It was found that women whose vitamin D levels increased the most or to at least 32 ng/mL had the greatest reduction in blood estrogens, which are a known risk factor for breast cancer (Mason, Menopause 2016). However, most of the reduction in blood estrogens appeared to be due to dieting itself, with estrogen levels falling, on average, by about 14.5% among women who didn't receive vitamin D compared to about 19.5% among those who did.

A study in Spain found that lower levels of vitamin D in the blood were associated with higher risks of bladder cancer. Compared to people with vitamin D levels of 30 ng/mL or above, the risk of bladder cancer was 83% higher among those with levels under 10 ng/mL, 67% higher among those with levels of 10 up to 15ng/mL, and 63% higher among those with levels of 15 up to 20 ng/mL. There was no statistically significant difference in risk, however, between those with levels of 20 up to 30 ng/mL compared to those above 30 ng/mL. (Amaral, JNCI 2012). Even greater increases were found with the risk of metastatic bladder cancer.

Laboratory studies suggest that vitamin D may inhibit pancreatic cancer cell growth and a review of five large epidemiologic studies concluded that higher levels of serum vitamin D were associated with a lower risk of developing pancreatic cancer.27 Compared to people whose serum vitamin D levels were less than 20 ng/mL, the risk of developing pancreatic cancer over the following 12 to 18 years was 25% lower among those with levels of 20 mg to 29 ng/mL, and 29% lower among those with levels above 30 ng/mL.

Vitamin D inhibits prostate cancer cells in laboratory studies. Whether or not vitamin D supplementation actually reduces the risk of prostate cancer is not known, but some studies do suggest an association between vitamin D levels and prostate cancer risk. For example, a large study in the U.S. found that both low and high vitamin D concentrations in the blood to be associated with increased risk of prostate cancer, particularly high-grade prostate cancer. The middle "sweet spot" associated with the lowest risk (about half the risk of the higher or lower levels) was between 23 ng/mL and 29 ng/mL, leading the researchers to write that the optimal range "for prostate cancer prevention may be narrow" Kristal, Canc Epi Biomark, Prev 2014. This finding is somewhat consistent with a smaller study of men in Chicago undergoing radical prostatectomy (due to indications of possible cancer), in which those found not to have advanced cancer had a median blood level of 27.0 ng/mL, which was only slightly higher than that of men with advanced cancer (22.7 ng/mL). However, the study found that men with advanced cancer were more likely to be black, and the black men were more likely to have lower levels of vitamin D (as seen in other studies), so when the results were analyzed just among blacks or among whites, there was no longer an association between vitamin D levels and advanced prostate cancer (Nyame, J Clin Oncol 2016).

A study of men aged 40 to 79 in the U.S. undergoing their first prostate biopsy for potential cancer, found that, in African American men, having a vitamin D level below 20 ng/mL was associated with increased odds of the biopsy showing prostate cancer. In addition, among both European American and African American men, having a level below 12 ng/mL was associated with a higher grade and stage of prostate cancer (Murphy, Clin Cancer Res, 2014).

A study of male smokers in Finland concluded that "men with higher vitamin D blood levels are at increased risk of developing prostate cancer," but this assertion has been called misleading since the risk increased only among men with calcium intakes of 1,338 mg per day or greater — an intake that substantially exceeds the recommended intake for adult men (1,000 mg). Increased calcium intake itself is a potential risk factor for prostate cancer.33, 34

An unusual report published in 2016 suggests that, for white women aged 55 years and older, vitamin D levels at or above 40 ng/mL, as compared to levels below 20 ng/mL, are associated with greater than a 65% reduction in risk of all invasive cancers combined, excluding skin cancer. This study, however, has several weaknesses including the fact that it was based on pooled data from two unrelated studies, one of which, run by the group GrassrootsHealth (which derives revenue from vitamin D home tests), was based entirely on a self-selected group of women who chose to maintain relatively high levels of vitamin D and self-reported their health status via a questionnaire. While the data indicated much lower rates of cancers (predominantly breast cancer) at increasing mean levels of vitamin D, the greatest decrease was seen as mean levels increased from below 20 ng/mL into the high 30s with no significant benefit indicated above that level. In addition, potential adverse effects were not assessed (McDonnell, PLOS ONE 2016).

 In summary, to potentially reduce the risk of cancer, it would seem reasonable to maintain a vitamin D level above 20 ng/mL and possibly into the upper 30's, but not necessarily higher. For prostate cancer, the "sweet spot" may be more limited -- to between 23 ng/mL and 29 ng/mL.

Overall mortality
A review of studies involving vitamin D concluded that supplementation with vitamin D3 reduced overall mortality among older adults significantly by 11%, while vitamin D2 had no overall effect (Chowdhury, BMJ 2014). The review also found that, in the U.S., about 13% of all deaths could be attributable to "suboptimal" vitamin D levels, which is even greater than the risk of death associated with physical inactivity. The review did not define exactly when, or how much, vitamin D is most effective, but you can find sensible guidelines in the Summary, above.

On a similar note, an analysis of data from 3,509 patients recovering from noncardiac surgery at the Cleveland Clinic found that those with higher levels of vitamin D in their blood were less likely to experience serious post-operative complications, including death (Turan, Anesth Analg 2014). In fact, compared to the level of complications in patients with serum vitamin D levels below 13 ng/mL, the risk of having serious complications fell to 65% when vitamin D levels were between 13 to 20 ng/mL, to 53% at levels between 20 and 27 ng/mL, and to 44% at levels between 27 and 36 ng/mL. Interestingly, at levels above 36 ng/mL, the relative odds of complications did not fall further and rose slightly, to 49%, consistent with other studies that have shown a reversal in benefits with vitamin D levels above approximately 35 ng/mL. The researchers suggest a trial be conducted in which vitamin D supplementation is given preoperatively.

For more information about the uses, see the article about Vitamin D in the Natural Products Encyclopedia on this Web site.

Quality Concerns and What CL Tested for:
Like other supplements, neither the FDA nor any other federal or state agency routinely tests calcium or vitamin D supplements for quality prior to sale. However, quality issues can include the following:

 
  • Labeled Amount Does the product really contain the labeled amount of vitamin D (and other key listed ingredients such as calcium, magnesium, and vitamin K)?
  • Purity Vitamin D supplements for bone health often include calcium as an ingredient. Calcium may potentially be contaminated with heavy metals such as lead, arsenic and cadmium. In children, infants, and fetuses, even low levels of lead can adversely affect neurobehavioral development and cognitive function. In adults, lead at somewhat higher levels can cause elevated blood pressure, anemia, and adversely affect the nervous and reproductive systems. Lead is of particular concern during pregnancy as the mother can deliver it to the fetus. Arsenic is a carcinogen and can damage organs. Cadmium is a probable carcinogen (i.e., cancer-causing agent), can be toxic to the kidneys, can soften the bones, causing bone pain, and may affect fetal development.
  • Ability to Break Apart for Absorption For a tablet to be most useful, it must fully disintegrate prior to leaving the stomach, delivering its contents for absorption in the gut. Some tablets are not properly made and can pass through your body completely or partially intact, depriving you of its ingredients. Remnants of such products are sometimes found in the stool. This happens, for example, when a tablet is too tightly compressed (too "hard") or is too thickly coated.
ConsumerLab.com, as part of its mission to independently evaluate products that affect health, wellness, and nutrition, purchased vitamin D supplements (as well as those with calcium, magnesium, and vitamin K) sold in the U.S. and tested them to determine whether they 1) possessed the claimed amount and form of vitamin D, calcium, magnesium, and vitamin K, 2) were able to disintegrate fully to be available for absorption and, 3) if they contained calcium, were free from unacceptable levels of lead, cadmium, and arsenic (see Testing Methods and Passing Score).

What CL Found:
Among the 21 vitamin D-containing supplements that ConsumerLab.com selected for testing, three products failed to meet our quality criteria. The 18 products that passed are listed as Approved in the table below. Also listed as Approved are 22 products that passed the same testing through CL's voluntary Quality Certification Program, bringing the total number of Approved vitamin D supplements in this report to 39.

As described below, all products which failed to be Approved were combination products; each was found to contain an incorrect amount of vitamin D or other key ingredient:
 
  • Country Life Bone Solid contained its claimed amount of vitamin D, but did not contain its claimed amounts of vitamin K. It was found contain only 76.2% (127 mcg) of the 166.67 mcg vitamin K1, and none (0 mcg) of the 1.67 mcg of vitamin K2 (MK-7) listed per capsule.
  • Shaklee OsteoMatrix was found to contain much more vitamin D than listed. These caplets contained 182.7% of the listed amount of D3. So the suggested daily dose of 4 caplets would provide 1,096 IU of vitamin D rather than 600 IU. There are potential risks with getting too much (over 4,000 IU per day) vitamin D from supplements (see Vitamin D Product Review, Concerns and Cautions).
  • Hero Nutritionals Yummi Bears , the only children's product not to pass testing, provided only 89.3 IU of the 100 IU of vitamin D listed on the label.

Cost:
To help you get the best value from vitamin D supplements, we calculated the cost to obtain a set amount (400 IU) of vitamin D from the products based on the prices we paid. As shown in the last column of the table below, this cost ranged from less than 1 cent for several products that contained only vitamin D to $2.60 cents for a product that contained additional ingredients.

Among products that were Approved, those with the lowest cost to obtain vitamin D were, by category: 
  • Vitamin D Only: To get a moderate dose of vitamin D (2,000 IU or less), Source Naturals Vitamin D-3 liquid drops cost less than 1 cent per drop (400 IU). Some advantages of taking vitamin D as liquid drops are that you can easily adjust the dose (5 drops is 2,000 IU) according to your needs and, if you don't like taking pills, the drops are tasteless and easy to add to a food or beverage (ideally those which contains fats or oils). Another option is TwinLab D3 Dots, small dissolvable tablets that provide 2,000 IU each and cost less than one cent. If you prefer a pill, Simply Right (Sam's Club) Vitamin D-3 provides 2,000 IU in a single softgel for just 2 cents. If you want a 1,000 IU pill, Swanson® High-Potency Vitamin D-3 also costs just 2 cents — but be aware that you are paying the same price for half as much vitamin D. For a higher dose, Nature's Bounty D3 costs just 10 cents for a 5,000 IU softgel (Be aware that too much vitamin D can be harmful. See How Much Is Too Much)
  • Children's Vitamin D: Carlson® Super Daily D3 (the only product tested in this category) costs just 3 cents per 400 IU drop and offers the benefits of a liquid (noted above) which can be very important for children. Just be careful not to shake out more than one drop if you intend to give 400 IU -- it's easy to double or triple a dose if you are not careful.
  • Vitamin D and Calcium: DG Health (Dollar General) provides 800 IU vitamin D3 and 600 mg calcium for 6 cents.
  • Children's Vitamin D and Calcium: Bayer Flintstones Healthy Bone Support Calcium & Vitamin D3 (26 cents for two gummies containing 250 IU of vitamin D and 250 mg of calcium))
  • Vitamins D and K: NOW Vitamin D-3 & K-2 (6 cents per capsule containing 1,000 IU of vitamin D and 45 mcg vitamin K2)
  • Vitamins D and K and Calcium: None passed testing.
  • Vitamin D, Calcium & Magnesium: Caltrate 600 + D Plus Minerals (8 cents for a tablet containing 800 IU of vitamin D, 600 IU of calcium, and 100 mg of magnesium)
  • Children's Products Containing Vitamin D, Calcium & Magnesium: ChildLife Liquid Calcium With Magnesium (the only product tested in this category) costs 53 cent per tablespoon, which provides 100 IU D3, 252 mg of calcium and 115 mg of magnesium.
  • Vitamins D and K, Calcium & Magnesium: It is very difficult to compare these products on cost as each has a unique formula with multiple and varied ingredients. However, the product with vitamin D at the lowest cost was Jarrow Formulas Bone Up (39 cents for 6 capsules providing 1,000 IU of vitamin D along with other vitamins and minerals)
Be aware that the suggested dosage of vitamin D varies widely across the products from 250 IU to 5,000 IU. Some of these amounts exceed the Upper Tolerable Intake Levels (ULs) for vitamin D for certain age groups and are footnoted as such next (see Concerns and Cautions for more about ULs).

Test Results by Product:
Listed below are the test results for 43 supplements containing vitamin D. Products are grouped by main ingredients, and there are subgrouping for children's products. Within each group, products are listed alphabetically. ConsumerLab.com selected 21 of these products. Twenty-two other products (each indicated with a CL flask) were tested at the request of their manufacturers/distributors through CL's voluntary Quality Certification Program and are included for having passed testing. Also listed are 2 products that are the same as ones that passed testing but are sold under different brand names.

Shown for each product are the claimed amount and form of the tested ingredient(s), serving size recommended on its label, price information and, for comparison purposes, the cost per 400 IU of vitamin D. Products listed as "Approved" met their label claims and ConsumerLab.com's quality criteria (see Passing Score). The full list of ingredients (including special dietary designations) is available for each product by clicking on the word "Full Ingredients" in the first column.

  Jump to results by ingredient: 
RESULTS OF CONSUMERLAB.COM TESTING OF VITAMIN D SUPPLEMENTS
(INCLUDING COMBINATIONS WITH VITAMIN K, CALCIUM AND/OR MAGNESIUM)
Click on beneath a product name to find a vendor that sells it.
To find retailers that sell some of the listed products click here.
Product Name, Amount Listed of Vitamin D per Unit, Serving Size, and Servings Per Day Suggested on Label

Click on "Ingredients" for Full Listing
Claimed Amount and Form of Vitamins D & K, Calcium and Magnesium Per Labeled Daily Serving --TEST RESULTS-- Cost for Daily Suggested Serving on Label

[Cost 400 per IU of Vitamin D]

Other Notable Ingredients/Features2

Price Paid
OVERALL RESULTS:

APPROVED or NOT
APPROVED
Contained Labeled Amount of Vitamins D & K, Calcium and Magnesium Did Not Exceed Contamination Limit for Lead, Arsenic and Cadmium1 Disintegrated Properly

(NA=Not Applicable)
Vitamin D Only:
Bluebonnet Earth Sweet® Chewable Vitamin D3 5000 IU (5,000 IU per chewable tablet; 1 chewable tablet, once daily)

Mfd. by Bluebonnet Nutrition Corporation
Ingredients
5,000 IU3
(D3)
APPROVED NA NA $0.18

[$0.01]

$15.96/90 chewable tablets
Garden of Life® Vitamin Code® Raw D3™ 5000IU (5,000 IU per vegetarian capsule; 1 vegetarian capsule, once daily)

Dist. by Garden of Life LLC
Ingredients
5,000 IU3
(D3)
APPROVED NA NA $0.31

[$0.02]

High omega-9 cracked-wall chlorella, RAW organic fruit & vegetable blend, RAW probiotic & enzyme blend

 Kosher, suitable for vegetarians, non-GMO, gluten free

$18.49/60 vegetarian capsules
GNC Vitamin D-3 1000 IU (1,000 IU per tablet; 1 tablet, once daily) 

Dist. by General Nutrition Corporation
Ingredients
1,000 IU
(D3)
APPROVED NA $0.06

[$0.02]

 Contains no wheat, gluten free, yeast free

$9.99/180 tablets
Jamieson™ D (1,000 IU per tablet; 1 tablet, once daily) 

Dist. by Jamieson Laboratories
Ingredients
1,000 IU
(D3)
APPROVED NA $0.09

[$0.04]

$9.15/100 tablets
Life Extension® Vitamin D3 (5,000 IU per softgel; 1 softgel, once daily) 

Dist. by Quality Supplements and Vitamins, Inc
Ingredients
5,000 IU3
(D3)
APPROVED NA NA $0.14

[$0.01]

$8.25/60 softgels
Metagenics® D3 1000™ (1,000 IU per tablet; 1 tablet, once daily)

Mfd. by Metagenics
Ingredients
1,000 IU
(D3)
APPROVED NA $0.16

[$0.06]

 Contains no wheat, gluten free

$18.75/120 tablets
Nature Made® Vitamin D 2000 IU (2,000 IU per tablet; 1 tablet, once daily) 

Dist. by Nature Made Nutritional Products
Ingredients
2,000 IU
(D3)
APPROVED NA $0.10

[$0.02]

 Gluten free, yeast free

$10.49/100 tablets
Nature's Bounty® D3 - 5000 IU (5,000 IU per softgel; 1 softgel, once daily) 

Mfd. by Nature's Bounty, Inc.
Ingredients
5,000 IU3
(D3)
APPROVED NA NA $0.10

[$0.018]

 Contains no wheat, gluten free, yeast free

$14.84/150 softgels
RiteAid® Pharmacy Vitamin D-3 (5,000 IU per softgel; 1 softgel, once daily)

Dist. by Rite Aide
Ingredients
5,000 IU3
(D3)
APPROVED NA NA $0.12

[$0.018]

 Contains no wheat, gluten free, yeast free

$12.49/100 softgels
Simply Right™ [Sam's Club] Vitamin D-3 (2,000 IU per softgel; 1 softgel, once daily) 

Dist. by SAM's West, Inc.
Ingredients
2,000 IU
(D3)
APPROVED NA NA $0.02

[$0.018]

 Contains no wheat, gluten free, yeast free

$8.48/400 softgels
Source Naturals® Vitamin D-3 (2,000 IU per 5 drops [0.16 mL]; 5 drops, once daily)

Dist. by Source Naturals, Inc.
Ingredients
2,000 IU
(D3)
APPROVED NA NA $0.01

[$0.018]

 Contains no wheat, gluten free, yeast free, hypoallergenic

$10.36/4 fl. oz. (118.28 mL) bottle (approx. 739 servings)
Swanson® High-Potency Vitamin D-3 Cholecalciferol (1,000 IU per tablet; 1 tablet, once daily) 

Dist. by Swanson Health Products
Ingredients
1,000 IU
(D3)
APPROVED NA NA $0.02

[$0.018]

$4.99/250 capsules
TwinLab® D3 Dots - All-Natural Tangerine Flavor (2,000 IU per tablet; 1 tablet, twice daily) 

Mfd. by TwinLab Corporation
Ingredients
4,000 IU4
(D3)
APPROVED NA $0.06

[$0.018]

$6.19/100 tablets
WHC UnoCardio® 1000 (1,00 IU per softel; 1 softgel, once daily)10

Dist. by QuattroMega Inc.
Ingredients
1,000 IU
(D3)
APPROVED

Also Approved for Omega-3
NA $0.73

[$0.29]

Omega-3 fish oil (EPA & DHA)  

Suitable for pesco-vegetarians, gluten free

$43.95/60 softgels
Whole Foods™ Vitamin D3 (2,000 IU per softgel; 1 softgel, once daily)

Dist. by Whole Foods Market
Ingredients
2,000 IU
(D3)
APPROVED NA NA $0.06

[$0.01]

$13.99/250 softgels
Similar to Approved Vitamin D-Only Products*:
Puritan's Pride® Sunvite® Mega-Potency Vitamin D3 5000 IU (5,000 IU per softgel; 1 softgel, once daily)

Mfd. by Puritan's Price, Inc.
Ingredients
Similar to Nature's Bounty® D3 - 5000 IU. $0.08

[$0.018]

 Contains no wheat, gluten free, yeast free

$16.999/200 softgels
Vitamin World® Sunvite® Vitamin D3 (5,000 IU per softgel; 1 softgel, once daily)

Mfd. by Vitamin World, Inc.
Ingredients
Similar to Nature's Bounty® D3 - 5000 IU. $0.10

[$0.018]

 Contains no wheat, gluten free, yeast free

$49.9910/500 softgels
Children's Products Containing Vitamin D:
Carlson® Super Daily D3 for Baby (400 IU per drop [0.027 mL]; 1 drop, once daily)

Dist. by Carlson Division of J.R. Carlson Laboratories, Inc.
Ingredients
400 IU
(D3)
APPROVED NA NA $0.03

[$0.03]

Vitamin E

 Contains no wheat, gluten free

$10.79/0.36 fl. oz. [10.6 mL] bottle (approx. 365 servings)
Vitamin D & Calcium:
Andorra Life Collagen Calcium (100 IU per capsule; 4 capsule, once daily)

Dist. by Andorra Life LLC
Ingredients
400 IU
(D3)

300 mg
(KoACT® calcium collagen chelate)
APPROVED NA $2.60

[$2.60]

Zinc, rose hips powder

 Contains no wheat

$39.00/60 capsules
Bayer Citracal® Petites (250 IU per tablet; 2 tablets, twice daily)

Dist. by Bayer HealthCare LLC
Ingredients
1,000 IU
(D3)

800 mg
(Calcium citrate)
APPROVED $0.24

[$0.10]

$12.19/200 coated tablets
CVS/pharmacy™ Calcium (400 IU per gummy; 2 gummies, once daily)

Dist. by CVS Pharmacy, Inc.
Ingredients
800 IU
(D3)

500 mg
(Tricalcium phosphate)
APPROVED NA $0.51

[$0.26]

 Contains no wheat, gluten free

$12.79/50 gummies
DG Health™ [Dollar General] Calcium 600mg (800 IU per caplet; 1 caplet, once or twice daily)

Dist. by Dolgencorp, LLC
Ingredients
800 IU to 1,600 IU
(D3)

600 mg to 1,200 mg
(Calcium carbonate)
APPROVED $0.06-$0.12

[$0.03]

 Contains no wheat, gluten free, yeast free

$3.50/60 caplets
Finest Nutrition [Walgreens] Calcium (500 IU per softgel; 2 softgels, once daily) 

Dist. by Walgreen Co.
Ingredients
1,000 IU
(D3)

1,200 mg
(Calcium carbonate)
APPROVED NA $0.21

[$0.08]

 Contains no wheat, gluten free, yeast free

$10.49/100 softgels
Nature's Way® Alive!® Calcium Gummies Plus Vitamin D3 (500 IU per gummy; 2 gummies, twice daily) 

Dist. by Nature's Way Products, LLC
Ingredients
2,000 IU
(D3)

1,000 mg
(Tricalcium phosphate)
APPROVED NA $0.64

[$0.13]

Phosphorus, orchard fruits™/garden veggies™ blend

 Contains no wheat, gluten free, yeast free

$9.60/60 gummies
Solgar® Calcium Citrate With Vitamin D3 (150 IU per tablet; 4 tablets, once daily) 

Mfd. by Solgar, Inc.
Ingredients
600 IU
(D3)

1,000 mg
(Calcium citrate)
APPROVED $0.33

[$0.22]

 Kosher, contains no wheat, gluten free, yeast free

$19.76/240 tablets
Spring Valley™ [Walmart] Calcium (500 IU per softgel; 2 softgels, once daily) 

Dist. by Wal-Mart Stores, Inc.
Ingredients
1,000 IU
(D3)

1,200 mg
(Calcium citrate)
APPROVED NA $0.11

[$0.04]

 Contains no wheat, gluten free, yeast free

$7.98/150 softgels
Trader Joe's® Calcium Citrate With Vitamin D (133.3 IU per tablet; 3 tablets, once daily)

Dist. by Trader Joe's
Ingredients
400 IU
(D3)

1,000 mg
(Calcium citrate)
APPROVED $0.50

[$0.50]

 Gluten free

$14.97/90 tablets
Children's Products Containing Vitamin D & Calcium:
Bayer Flintstones™ Healthy Bone Support Calcium & Vitamin D3 (125 IU per gummy; 2 gummies, once to twice daily5)

Dist. by Bayer HealthCare LLC
Ingredients
250 IU to 500 IU
(D3)

250 mg to 500 mg
(Tricalcium phosphate)
APPROVED NA $0.26-$0.53

[$0.42]

Phosphorus, sodium

$17.09/130 gummies
Hero Nutritionals® Yummi Bears® Vegetarian Sour Calcium + Vitamin D3 (100 IU per gummy; 3 gummies, 1/3 to once daily6)

Dist. by Hero Nutritionals, Inc.
Ingredients
100 IU to 300 IU
(D3)

125 mg to 375 mg
(Tricalcium phosphate)
NOT
APPROVED
Found only 89.3 IU vitamin D per gummy (89.3% of labeled amount) NA $0.14-$0.43

[$0.58]

Phosphorus, sodium

 Contains no wheat, gluten free, yeast free

$12.97/90 gummies
Vitamin D & Vitamin K:
NOW® Vitamin D-3 & K-2 (1,000 IU per veg capsule; 1 veg capsule, once to twice daily)

Mfd. by NOW Foods
Ingredients
1,000 IU to 2,000 IU
(D3)

45 mcg to 90 mcg
(K2)
APPROVED NA NA $0.06-$0.12

[$0.02]

Vitamin C

 Contains no wheat, gluten free

$6.99/120 veg capsules
USANA® Vitamin D (2,000 IU per tablet; 1 tablet, once daily)

Dist. by USANA Health Sciences, Inc.
Ingredients
2,000 IU
(D3)

30 mcg
(MK-4 & MK-7)
APPROVED NA $0.24

[$0.05]

$19.95/84 tablets
Vitamin D, Vitamin K & Calcium:
Viactiv® Calcium Plus D - Milk Chocolate (500 IU per soft chew; 1 soft chew, once to twice daily)

Dist. by Viactiv Lifestyle, LLC
Ingredients
500 IU to 1,000 IU
(D3)
40 mcg to 80 mcg
(K1)

500 mg to 1,000 mg
(Calcium carbonate)
APPROVED NA $0.09-$0.18

[$0.07]

Sodium

$10.39/115 soft chews
Vitamin D, Calcium & Magnesium:
Bayer Citracal® Slow Release 1200 (500 IU per coated tablet; 2 coated tablets, once daily)

Dist. by Bayer HealthCare LLC
Ingredients
1,000 IU
(D3)

1,200 mg
(Calcium carbonate and calcium citrate)

80 mg
(Magnesium hydroxide, magnesium silicate and magnesium stearate)
APPROVED NA $0.27

[$0.11]

Sodium

Slow Release

$10.92/80 coated tablets
Caltrate® 600 + D Plus Minerals (800 IU per tablet; 1 tablet, once to twice daily)

Dist. by Pfizer
Ingredients
800 IU to 1,600 IU
(D3)

600 mg to 1,200 mg
(Calcium carbonate)

50 mg to 100 mg
(Magnesium oxide and magnesium stearate)
APPROVED $0.13-$0.27

[$0.07]

Zinc, copper, manganese, boron

$15.99/120 tablets
GNC Calcium Plus® 1000 With Magnesium & Vitamin D-3 (266.67 IU per caplet; 3 caplets, once daily)

Dist. by General Nutrition Corporation
Ingredients
800 IU
(D3)

1,000 mg
(Calcium carbonate)

500 mg
(Magnesium oxide)
APPROVED $0.22

[$0.11]

 Contains no wheat, gluten free, yeast free

$12.99/180 caplets
Kirkland Signature™ [Costco] Calcium Citrate Magnesium And Zinc (400 IU per tablet; 2 tablets, once daily)

Dist. by Costco Wholesale Corporation
Ingredients
800 IU
(D3)

500 mg
(Calcium citrate)

80 mg
(Magnesium oxide, magnesium stearate)
APPROVED $0.05

[$0.02]

Vitamin B6, zinc, copper, manganese, boron

 Gluten free

$12.49/500 tablets
Nature Made® Calcium Magnesium Zinc (200 IU per tablet; 1 tablet, once to three times daily)

Dist. by Nature Made Nutritional Products
Ingredients
200 IU to 600 IU
(D3)

333 mg to 999 mg
(Calcium Carbonate)

133 mg to 399 mg
(Magnesium oxide)
APPROVED
(Also approved for Zinc)
$0.04-$0.13

[$0.09]

Zinc

 Gluten free, yeast free

$12.99/300 tablets
Nutrilite® Cal Mag D Advanced (200 IU per tablet; 3 tablets, once daily)

Dist. by Amway Corp.
Ingredients
600 IU
(D3)

600 mg
(Calcium carbonate and calcified seaweed)

200 mg
(Magnesium oxide)
APPROVED $0.48

[$0.32]

Zinc, manganese

 Kosher

$28.84/180 tablets
Rainbow Light® Food Based Calcium™ (500 IU per tablet; 1 tablet, once to twice daily)

Dist. by Rainbow Light Nutritional Systems®
Ingredients
500 IU to 1,000 IU
(D3)

500 mg to 1,000 mg
(Calcium carbonate, calcium amino acid chelate and calcium citrate-malate)

250 mg to 500 mg
(Magnesium oxide and magnesium aspartate)
APPROVED $0.33-$0.67

[$0.27]

Betaine HCl, stinging nettle, horsetail, organic spirulina

 Gluten free

$59.97/180 tablets
Children's Products Containing Vitamin D, Calcium & Magnesium:
ChildLife® Liquid Calcium With Magnesium - Natural Orange Flavor (100 IU per tbsp.; 1 tbsp, 1/3 to twice daily7)

Dist. by ChildLife
Ingredients
33.3 IU to 200 IU
(D3)

84 mg to 504 mg
(Calcium citrate)

38.3 mg to 230 mg
(Magnesium citrate)
APPROVED NA $0.18-$1.06

[$2.12]

Zinc

 Contains no wheat, gluten free, yeast free

$16.99/16 fl. oz. [474 mL] bottle (approx. 32 servings)
Vitamin D, Vitamin K, Calcium & Magnesium:
Country Life® Bone Solid® (166.67 IU per capsules; 6 capsules, once daily)

Mfd. by Country Life, LLC
Ingredients
1,000 IU
(D3)
1,000 mcg
(K1)
10 mcg
(MK-7 K2)

1,011 mg
(Microcrystalline hydroxyapatite and calcium fructoborate)

500 mg
(Magnesium oxide, magnesium ascorbate, magnesium alpha-ketoglutarate, magnesium aspartate, magnesium citrate, magnesium taurinate)
NOT
APPROVED
Found only 127 mcg vitamin K1 (76.2% of labeled amount) and 0 mcg vitamin K2 (MK-7) per capsule NA $0.60

[$0.24]

Phosphorus, zinc, copper, manganese, chromium, potassium, microcrystalline hydroxyapatite (MCHA), calcium fructoborate (FruiteX-B®)

 Contains no wheat, gluten free, yeast free

$17.99/180 capsules
Jarrow Formulas® Bone-Up (166.67 IU per capsule; 6 capsules, once daily) 

Dist. by Jarrow Formulas®
Ingredients
1,000 IU
(D3)

45 mcg
(MK-7 K2)

1,000 mg
(StimuCal™ microcrystalline hydroxyapatite)

500 mg
(Magnesium oxide)
APPROVED NA $0.59

[$0.24]

Vitamin C, zinc, copper, manganese, potassium, boron

 Non-GMO, contains no wheat, no gluten

$11.89/120 capsules
Nature's Way® Alive!® Calcium Bone Formula (500 IU per tablet; 4 tablets, once daily)

Dist. by Nature's Way Products, LLC
Ingredients
2,000 IU
(D3)

100 mcg
(MK-7 K2)

1,000 mg
(Calcium from Aquamin® calcified mineral source Red Algae Lithothamnion sp., organic kale, organic spinach and organic collard greens)

500 mg
(Magnesium citrate, magnesium oxide and magnesium Aquamin® calcified mineral source Red Algae Lithothamnion sp.)
APPROVED $0.80

[$0.16]

Vitamin C, sodium, strontium, silica, boron, vanadium

 Contains no wheat, gluten free, yeast free

$23.99/120 tablets
Shaklee® OsteoMatrix® (150 IU per caplet; 4 caplets, once daily)

Dist. by Shaklee Corporation
Ingredients
600 IU
(D3)

40 mcg
(K1)

1,000 mg
(Calcium carbonate, calcium citrate and calcium citrate malate)

400 mg
(Magnesium oxide, magnesium citrate and magnesium gluconate)
NOT
APPROVED
Found 274 IU vitamin D per caplet (182.7% of labeled amount) $0.56

[$0.37 based on amount claimed]
[$0.20 based on amount found]

Zinc, copper, manganese, sodium

 Kosher, gluten free

$16.75/120 caplets
USANA® Active Calcium™ (100 IU per tablet; 4 tablets, once daily)

Dist. by USANA Health Sciences, Inc.
Ingredients
400 IU
(D3)

60 mcg
(K1)

800 mg
(Calcium citrate and calcium carbonate)

400 mg
(Magnesium citrate, magnesium amino acid chelate and magnesium oxide)
APPROVED $0.68

[$0.68]

Boron

 Contains no wheat, gluten free, yeast free

$18.95/112 tablets

Tested through CL's Quality Certification Program prior to, or after initial posting of this Product Review.

* Product identical in formulation and manufacture to a product that has passed testing but sold under a different brand. For more information see CL's Multi-Label Testing Program.

 - Canadian Product

 1 Products were only tested if they contained calcium.
 2 Not tested but claimed on label.
 3 Exceeds Upper Tolerable Limit (UL) for Vitamin D for all ages. The UL for children 1 to 3 years of age is 2,500 IU of vitamin D, for children 4 to 8 years of age is 3,000 IU of vitamin D, for children and adults 9 plus years of age is 4,000 IU of vitamin D.
 4 Exceeds Upper Tolerable Limit (UL) for Vitamin D for children under 9 years of age, and is at the UL for all children and adults 9 plus years of age . The UL for children 1 to 3 years of age is 2,500 IU of vitamin D, for children 4 to 8 years of age is 3,000 IU of vitamin D, for children and adults 9 plus years of age is 4,000 IU of vitamin D.
 5 Label states: "Children 2 to 3 years of age: Chew two gummies daily. Adults and children 4 years of age and older: Chew four gummies daily)."
 6 Label states: "As a dietary supplement, parent may give each child up to three (3) beats per day."
 7 Label states: "For infants 6 months - 1 year: 1 teaspoon daily. For children 1 - 3 years: 2 teaspoons daily. For children 4 - 8 years: 1 tablespoon daily. For children 9 - 12 years: 2 tablespoons daily."
 8 Price was rounded up to $0.01.
 9 Price based on listed price from puritanspride.com.
 10 Product added on 3/17/2017.

Unless otherwise noted, information about the products listed above is based on the samples purchased by ConsumerLab.com (CL) for this Product Review. Manufacturers may change ingredients and label information at any time, so be sure to check labels carefully when evaluating the products you use or buy. If a product's ingredients differ from what is listed above, it may not necessarily be of the same quality as what was tested.

The information contained in this report is based on the compilation and review of information from product labeling and analytic testing. CL applies what it believes to be the most appropriate testing methods and standards. The information in this report does not reflect the opinion or recommendation of CL, its officers or employees. CL cannot assure the accuracy of information.
Copyright ConsumerLab.com, LLC, 2015. All rights reserved. Not to be reproduced, excerpted, or cited in any fashion without the express written permission of ConsumerLab.com LLC.


ConsumerTips:

What to Consider When Buying:
 Before buying a vitamin D supplement, be aware that vitamin D can be obtained in sufficient amounts from exposure to sunlight, fortified milk (400 IU per quart or 100 IU per cup), and other fortified foods (e.g., many breakfast cereals and nutrition bars, some brands of orange juice, yogurt, margarine, and soy beverages). Fatty fish are also good sources of vitamin D. Small amounts of vitamin D are found in beef liver, cheese, egg yolks, and mushrooms.

Ten to fifteen minutes of sun exposure at least two times per week to the face, arms, hands, or back without sunscreen is usually sufficient to provide adequate vitamin D. It has been estimated that getting the equivalent of a 1,000 IU dose of vitamin D requires exposing the face, hands and arms to full sunlight at noon for 6 to 15 minutes in Miami or 9 to 19 minutes during non-winter months in Boston, based on a darker-skinned Caucasian. Times are shorter by about 33% for people with very fair skin and double for those with dark skin. To get only 400 IU, times would be 40% as long. All of these exposures are significantly less than the amount required to cause sunburn. (It should be noted that sun exposure cannot result in toxic levels of vitamin D because excessive exposure to sunlight degrades previtamin D3 (which is normally converted by sunlight into vitamin D3 in the skin) and degrades vitamin D3 itself (Holick, N Engl J Med 2007)). Nevertheless, the researchers who made these calculations suggest that oral supplements of vitamin D would probably represent the safest way to increase vitamin D status due to the difficulty getting just the right amount of sun exposure and the detrimental side effects of UV exposure.12

Furthermore, inadequate vitamin D intake is common in people who live in northern climates (north of a line from Boston to the northern border of California), especially if they are dark-skinned. Also, increased concern about skin cancer has caused people to avoid the sun or use sunscreen. This creates a potential risk of reduced vitamin D.

Older individuals are at increased risk of vitamin D insufficiency (Omdahl, Am J Clin Nutr 1982; Holick, J Clin Endocrinol Metab 2005; van der Wielen RP, Lancet 1995), particularly the very old (Passeri, J Clin Endocrinol Metab 2003). This may be due to a variety of factors, including reduced time outdoors with reduced skin exposure to the sun. A study showed that surgical skin samples from older people was less able to convert a vitamin D precursor compound toward vitamin D than skin from younger individuals and there was less of this precursor in the top (epithelial) layer of older skin - although amounts in the lower layer were the same (MacLaughlin J, J Clin Invest 1985). However, an experiment in living people found that exposing the backs or entire bodies of old and young people to equal amounts of light produced the same amounts of vitamin D (Davie, Clin Sci 1980).

People who are obese also tend to have a low plasma concentration of 25-hydroxyvitamin D, as subcutaneous fat may sequester the vitamin.

Because vitamin D is a fat-soluble vitamin, people with reduced ability to absorb fat in the gut may also require vitamin D supplementation.

Vitamin D oral sprays are commercially available (although not legally, as sprays are not considered dietary supplements) and have been promoted as an alternative for people with gastrointestinal issues (such as Crohn's disease, ulcerative colitis and steatorrhea) which can reduce intestinal absorption of vitamin D. This is based on the premise that sprayed vitamin D can be absorbed directly through the lining of the mouth. However, there do not appear to be studies proving that oral absorption actually occurs. Nevertheless, sprays can certainly work as well as any other type of oral delivery, possibly because one is still swallowing 
the liquid. In fact, a small study in India in people having various bowel diseases and very low levels of vitamin D found that 1,000 IU of vitamin D3 given as an oral spray daily for one month significantly increased blood levels of vitamin D (by an average of 10.5 ng/mL) compared to the same dose of D3 taken as a softgel (which resulted in an average increase of 4 ng/mL) (Satia, Nutr J 2015). In the same study, vitamin D3 spray also significantly increased vitamin D blood levels of healthy people compared to supplementation with the softgel — resulting in average increases of 8 ng/mL and 4 ng/mL, respectively. However, this may not have been a fair comparison, since both the spray and capsules were taken 30 minutes following a meal. This is not an ideal way to take vitamin D from a pill, which should be taken with a meal for best absorption -- and properly taking 1,000 IU of vitamin D as a softgel daily should increase blood levels by about 10 ng/mL in a lean individual. A study in Ireland compared 3,000 IU of vitamin D given daily to healthy adults as an oral spray (DLux3000 from Better You, UK, which includes lecithin -- a fat) or as a capsule. After 4 weeks, the spray and capsule  were found to increase vitamin D levels, respectively, by 10.6 ng/mL and 12.2 ng/mL, with the difference between the two not statistically significant. No instruction was given to take either formulation at the time of a meal, perhaps explaining the modest increases despite the large dose (Todd, Br J Nutr 2016). Sprays tend to be more expensive: about 8 to 10 cents per 1,000 IU dose. The same dose can be obtained from a vitamin D liquid drop or pill for little as 1 or 2 cents as shown in this Review. In short, in healthy individuals, non-sprays can be as effective as sprays and are less expensive. In people with intestinal absorption problems, either may raise vitamin D levels but absorption may be greater with a spray.

When buying vitamin D, be aware that it is measured in International Units (IU) of vitamin D activity or as micrograms of cholecalciferol (D3) or ergocalciferol (D2). One microgram is equivalent to 40 IU.

A small news article appeared in 2010 regarding research on the content of vitamin D supplements presented at a Multiple Sclerosis conference by a team at Johns Hopkins University. The results showed the mean actual dose in 10 supplements to be only 33.5% of the labeled dose, with a range from 0.24% to 81.7%. ConsumerLab.com contacted the research team to learn more about the findings. We spoke with Dr. Norman Haughey who oversaw the testing. It appears that the report was preliminary: The team had not yet performed extraction efficiency testing, i.e., making sure that they got all of the vitamin D out of the tested samples. Poor extraction recovery will yield low results and is a well-known problem with vitamin D in supplements where other components of the product can interfere with measurements.

What to Consider When Using:
In November 2010, recommended intake levels of vitamin D for Americans and Canadians were increased by the Institute of Medicine (IOM). For infants up to 12 months of age, the daily Adequate Intake (AI) was set at 400 IU (10 micrograms). Note that the AI is only relevant if an infant is not getting adequate exposure to sunlight. The following Recommended Dietary Allowances (RDAs) were established for other age groups: 600 IU (15 micrograms) for people aged 1 to 70 and 800 IU (20 micrograms) for those aged 71 and older.17

While some studies suggest that even higher intakes of vitamin D may be useful for a range of purposes, the IOM considered the data behind those suggestions preliminary. Nevertheless, based on studies that showed a decreased risk of cancer associated with increased vitamin D intake and/or blood levels, the Canadian Cancer Society recommends a daily intake of 1,000 IU for adults in the fall and winter. The Canadian recommendation reflects the fact that there is reduced sun exposure in northern latitudes. The recommendation is for 1,000 IU intake year-round for people who are older, have dark skin, don't go outside often, or wear clothing that covers most of their skin.

In infants, the IOM and American Academy of Pediatrics recommend a vitamin D target level of 20 ng/dL. Both organizations recommend 400 IU daily to achieve this level (Wagner, Pediatrics 2008). A convenient way to give this is to add a single 400 IU drop of a liquid vitamin D (such as Carlson Super Baby Daily D3 — 400 IU per drop -- as listed in the Results table above) to bottled milk per day.Supplementation should occur even if children are breastfed -- particularly if breastfeeding continues for more than one year: A study in Canada found that without supplementation, the probability of breastfed children being vitamin D deficient was 16% by age 2 and 29% by age 3 (Darmawikarta, Am J Pub Health 2016).

Some groups suggest higher levels in infants of 30-60 ng/dL, however, this is controversial (Endo Soc, J C Endrocrinol Metab, 2011; Can Paed Soc Paediatr Child Health 2007). A clinical study shows that 400 IU of vitamin D3 daily was adequate to achieve the target level of 20 ng/dL in 97.5% of healthy, breastfed infants after 3 months of treatment. Higher doses were also studied (800 IU, 1200 IU, and 1600 IU daily). The 1600 IU dose caused excessively high levels in many infants. Additionally, there was no difference in bone mineral content between the lower and higher doses after a year of treatment (Gallo, JAMA 2013). These data confirm that 400 IU daily is an adequate dose for most healthy infants. Higher doses should be used cautiously. See Concerns and Cautions.

For building bone in young girls (ages 9 to 13), a study found benefit with a supplement providing, on a daily basis, 800 mg of calcium (from calcium citrate and calcium carbonate), 400 IU of vitamin D2, and 400 mg of magnesium (from magnesium citrate) when taken regularly for six months (Greene, Osteoporosis Int 2011). The supplement (Active Calcium Chewable, USANA Health Sciences, Inc. - not tested in this Review) was taken as four chewable tablets, two with breakfast and two with dinner as it is best to divide doses when taking large amounts of minerals. Another study found that a weekly dose of 1,400 IU or 14,000 IU of vitamin D3 resulted in significant increases in the mineral content of hip bones -- although the majority of the girls started the study deficient in vitamin D. Interestingly, the higher weekly dose appeared to have somewhat less effect than the lower dose (Al-Shaar, Bone 2013).

For reducing the risk of fracture of the hip and nonverterbral bone in people 65 years of age or older, maintaining a serum vitamin D level above 24 ng/mL appears to be beneficial.39

For reducing the risk of cardiovascular disease and stroke in men, 600 IU or more of vitamin D per day from food and supplements may be helpful. (A similar cardiovascular benefit in women has not been shown).21

For reducing high blood pressure in people already taking a calcium channel blocker (nifedipine), 2,000 IU of vitamin D3 per day has been shown reduce systolic and diastolic pressures by a few points (Chen, Atherosclerosis 2014). However, a study giving 100,000 IU of vitamin D3 quarterly showed no benefit (Witham, JAMA 2013) and a review of 46 studies concluded that vitamin D appears ineffective for lowering high blood pressure (Beveridge, JAMA Int Med 2015).

For improving cholesterol levels in people already taking a statin medication, 2,000 IU of vitamin D3 per day has been shown to be effective, particularly among people with lower blood levels of vitamin D (Qin, Clin Nutr 2015).

For improving balance and muscle strength in older adults 800 to 1,000 IU daily of vitamin D may be beneficial.30 (Cangussu, Osteoporos Int 2015).In older women deficient in vitamin D, 4,000 IU daily of vitamin D3 has been shown to increase muscle fiber size, although not physical functioning (Ceglia, J Clin Endocrin Metab 2013).

For reducing symptomatic pain in fibromyalgia, 2,400 IU of vitamin D3 for people with vitamin D levels below 24 ng/mL, and 2,400 IU for those starting with levels between 24 ng/mL and 32 ng/mL have been successfully used (although treatment was stopped as a precaution when levels exceeded 48 ng/mL, which occured with several patients) (Wepner, Pain 2013).

For reducing menstrual pain in women, a single high dose of 300,000 IU vitamin D3 taken 5 days before the start of menstruation may be beneficial for the following two months.29 However, there are potential concerns with such a high dose (see (Concerns and Cautions).

During pregnancy, raising vitamin D blood levels to 32 ng/mL in a population with a high rate of vitamin D deficiency decreased by half the incidence of pre-term labor, pre-eclampsia, and/or gestational diabetes. Women were given vitamin D starting at week 20 and dosage depended on initial vitamin D status, ranging from one dose of 60,000 IU to monthly doses of 120,000 IU for two to four months (Sablok, Clin Endocrinol 2015).

For reducing the risk of exacerbations of COPD, 100,000 IU of vitamin D monthly or 120,000 IU every two months has been helpful among people deficient in vitamin D (Martineau, Lancet Resp Med 2014; Lehouck, Ann Intern Med 2012).

D2 or D3?
A number of studies have compared the abilities of vitamin D2 and vitamin D3 to raise vitamin D blood levels. Some have found them equally effective and some have found D3 more effective.2,3,5,7 As either form can be obtained inexpensively, it seems prudent to use supplements containing the D3 form, particularly as D2 may cause erroneously low vitamin D blood test results.

The potential advantage of D3 was recently illustrated in a small, but well-controlled, study in New Zealand in which 1,000 IU of vitamin D2 or D3, or a placebo, was given to healthy, non-obese individuals (ages 18 to 50) from the end of summer to the end of winter.40 On average, vitamin D levels dropped 18 ng/mL among those taking placebo and 8 ng/mL among those taking vitamin D2, while those taking D3 maintained their levels (at 32 ng/mL). It's worth noting that, unlike the U.S., there is little vitamin D fortification of milk or other foods in New Zealand. Also, due to the relatively high latitude of the study region (46o-- similar, for example, to Portland, Oregon) sunlight was relatively limited during the period of the study. Consequently, the dose of vitamin D3 given may have been greater than needed to maintain vitamin D levels in similar individuals in much of the U.S.

How Much Do You Need and "How Much is Too Much?"
After being ingested, both vitamin D2 and D3 are metabolized in the liver to form 25-hydroxy vitamin D and in the kidneys to 1,25-hydroxy vitamin D. Total serum levels (sometimes referred to as "blood levels") of 25-hydroxyvitamin D (also referred to as 25-(OH)D) are commonly used clinically to evaluate vitamin D status.

Based on the latest recommendations of the Institute of Medicine (IOM), the Estimated Average Requirement (EAR) for vitamin D among individuals ages 1 to 70 for bone growth and maintenance is daily intake of 400 IU of vitamin D, assuming minimal to no sun exposure, corresponding to a blood level of vitamin D (known as serum 25-(OH)D levels) of just 16 ng/mL. Some people will need more than this "average" requirement" so the IOM calculated an amount which would satisfy the requirements of practically all (97.5%) individuals; this amount, the Recommended Daily Allowance (RDA), is 600 IU of vitamin D, corresponding to a vitamin D blood level of 20 ng/mL. [Another way of expressing these levels is in nanomoles per liter (the unit of measurement commonly used in Canada): 1 ng/mL = 2.5 nmol/L, so 20 ng/mL = 50 nmol/L and 30 ng/mL = 75 nmol/L]. For individuals over age 70, the RDA is 800 IU.

From reviewing national surveys of blood levels, the IOM concluded that the majority of Americans and Canadians are getting enough vitamin D (as well as calcium), although elderly individuals are more likely to fall short on both and some adolescent girls may not get quite enough calcium. The IOM has determined that just 6% of U.S. population is vitamin D deficient (≤ 12.5 ng/mL), and 13% of Americans between the ages of 1 and 70 are "at risk" for vitamin D inadequacy (Manson, N Engl J Med 2016).

The IOM has cautioned that vitamin D blood levels ≥ 50 ng/mL (and daily intakes above 4,000 IU) can put people risk for adverse effects. This is based on studies showing an increase in adverse events (including overall mortality, some cancers, cardiovascular disease, and fractures and falls) associated with serum 25-(OH)D levels starting at about 30 ng/mL to 48 ng/mL and higher (75 to 120 nmol/L). Examples of such adverse events include the following:
  • A population study following nearly a quarter million people in Denmark for three years found that vitamin D levels of 20 to 24 ng/mL were associated with the lowest risk of dying during the study.35 A high serum level (56 ng/mL) was associated with a 42% higher risk of dying during the study than people with a level of 20 ng/mL.
  • An analysis of the vitamin D levels of more than 14,000 Americans aged 17 years and older found that mortality rates fell with increasing vitamin D levels until reaching 39 ng/mL (Kramer, PLoS One 2012). The lowest mortality rate was among those in the 30 to <40 ng/mL group, however, mortality rates were similar across the range of 20 to 40 ng/mL.
  • A population study following nearly half a million people aged 45 years and older for 4.5 years in Israel found that people with vitamin D levels of 20 to 36 ng/mL had the lowest risk of heart attack or death. Compared to people in this range, risk of heart attack and death was 91% higher among those with levels below 10 ng/mL, 26% higher among those with levels 10 to 20 ng/mL, and 13% higher when levels were above 36 ng/mL (Dror, J Clin Endocrinol Metab 2013).
  • A study comparing low-dose to high-dose vitamin D3, found that those achieving the highest blood levels fell about twice as often as those just above sufficiency (Bischoff-Ferrari, 2016).
A possible explanation for why taking high-dose vitamin D has been linked with muscle weakness and increased risk of fractures and falls, comes from a study among professional athletes in Europe which found that a dose of 70,000 IU vitamin D3 taken weekly for three months increased the production of an enzyme (24-hydroxylase) which breaks down vitamin D in the blood and inactivates the hormonally active form of vitamin D in the body. The increase in this enzyme persisted for up to 6 weeks after supplementation was discontinued (Owens, Med Sci Sports Exerc 2017). The researchers recommended that "lower doses of vitamin D3 ingested frequently may be most appropriate and gradual withdrawal from supplementation as opposed to rapid withdrawal may be favorable."

It would seem prudent, based on the latest IOM recommendations and recent studies, to maintain blood levels of vitamin D above 20 ng/mL, but not much higher than 30 ng/mL. Misinterpretation and misapplication of the IOM reference standards can have adverse implications for patient care, including unnecessary vitamin D screening and supplementation. For healthy patients, routine screening is not recommended (Manson, N Engl J Med 2016).

With regard to the combination of vitamin D and calcium, an analysis of clinical trials involving older adults found a 9% lower risk of dying over a 3-year period among those who took vitamin D along with calcium supplementation (1,000 mg) compared to those not taking these supplements.35 The benefit was only found with low dose (400 IU) and not higher dose (800 IU or more) vitamin D, and only with daily dosing as opposed to intermittent (e.g., annual) dosing of vitamin D. The benefit was not seen among people taking vitamin D without calcium, although this does not suggest a protective effect of calcium. It is difficult to draw useful conclusions for individuals from this study particularly because blood levels of vitamin D were not part of the analysis, i.e., it is possible that results would vary depending one's vitamin D status.

From reviewing national surveys of blood levels, the IOM concluded that the majority of Americans and Canadians are getting enough vitamin D (as well as calcium), although elderly individuals are more likely to fall short on both and some adolescent girls may not get quite enough calcium.

It should be noted that some researchers have set higher benchmarks for vitamin D sufficiency typically 30 ng/mL or above. For example, using 30 ng/mL as the benchmark for sufficiency and less than 15 ng/mL to define deficiency, a study of vitamin D levels concluded that 61% of American children and adolescents had insufficient levels of vitamin D and an additional 9% were deficient. Deficient children tended to have higher blood pressure and lower levels of HDL ("good") cholesterol than other children. Older children were more likely to be deficient, as were those who were obese, drank milk less than once a week, or spent more than four hours a day with TV, video, or computers. Those who used vitamin D supplementation were less likely to be deficient.4

When laboratories report your vitamin D level, they will typically show a "standard range" or "reference range" of about 20 ng/mL to 100 ng/mL. These ranges vary with the laboratory and are based on levels the lab has found in 95% of a "healthy" population. However, these numbers do not reflect the range which has been recommended by the Institute of Medicine, as described above, which falls at the lower end of this range. If your level is 25 ng/mL, for example, you should not interpret the results as suggesting that your level is low. Similarly, if your level is 60 ng/mL, this does not mean your level is ideal -- current evidence, as noted in the Review, suggests that it is too high.

A rule of thumb for raising serum levels of 25-hydroxyvitamin D is that about 100 IU of vitamin D2 or D3 daily will raise serum levels by about 1 ng/mL in an adults and adolescents. However, more vitamin D is required by obese individuals to get this same increase: A study of obese adolescents found that about 200 IU was needed to for every 1 ng/mL increase in serum levels.26 With moderate (1,000 IU per day) supplementation, it has been shown to take about 6 weeks for serum levels to reach their peak. For example, during winter with no significant sun exposure, supplementation with 1,000 IU has been shown to increase levels of around 20 ng/mL up to about 30 ng/ml at 6 weeks. In such a scenario, sun exposure or a dosage higher than 1,000 IU would be necessary to further elevate levels above 30 ng/mL.4

In people who are black, the traditional measurement of vitamin D levels using total serum 25-hydroxyvitamin D may not be appropriate as it may overestimate vitamin D deficiency. Due to a genetic variant, many blacks have lower levels of binding protein for vitamin D (which binds 85 to 90% of total vitamin D), allowing more of the total vitamin D to be bioavailable, i.e., available for use. Consequently, although total vitamin D levels may seem low in blacks, the bioavailable amount of vitamin D may be sufficient. In fact, a study in Baltimore found mean total vitamin D levels to be 15.6 ng/mL in blacks and 25.8 ng/mL in whites, while amounts of bioavailable vitamin D were the same in both groups. Furthermore, bone mineral density and calcium levels were higher among the blacks than whites (Powe, NEJM 2013). The measurement of bioavailable vitamin D may, therefore, be more accurate for assessing the vitamin D status of black individuals. Unfortunately, this is more difficult than measuring total vitamin D and currently relies on an indirect method in which vitamin D-binding protein must be measured and the amount of vitamin D bound to the protein is subtracted from total vitamin D.

Vitamin D Tests — Not Always Reliable
Tests to determine vitamin D levels may not always be reliable. Thousands of vitamin D readings taken in 2007 and 2008 turned out to be too high because the test was not properly performed. Newer, faster, and less expensive immunoassay tests are now widely used. However, a preliminary study found these devices to yield inaccurate results at least 40% of the time — tending to provide low results.38 In the study, blood samples were run with an older established method (LC/MS) and two newer devices. The established method found vitamin D deficiency (less than 20 ng/mL) in 20% of the samples, but the Abbot Architect and Siemens Centaur-2 immunoassay devices respectively found deficiency in 28% and 44% of the samples, classifying some people as deficient who were not. The inaccuracies tended to occur with samples containing vitamin D2. If your test results don't seem to jive with your vitamin D intake and level of sun exposure, consider a retest using the LC/MS method, particularly if you are getting vitamin D2 from supplements or foods.

Take Vitamin D with Food
It is not uncommon for a person being treated for vitamin D deficiency to fail to achieve adequate serum levels. A small but striking study at the Cleveland Clinic Foundation Bone Clinic suggests that one reason may be that such people are taking vitamin D supplements on an empty stomach or with a small meal, usually breakfast or lunch.25 In the study, 17 such people were instructed, instead, to take the same supplement with the largest meal of the day, usually supper. After 2 to 3 months, researchers found that serum vitamin D levels had increased, on average, by 56.7%. This magnitude of increase was seen across a wide range of vitamin D dosage and forms (D2 and D3). As vitamin D is fat soluble, it is generally recommended that it be taken with a meal containing fats. However, based on this study, it may be best to take vitamin D with your largest meal of the day, which is likely to contain the most fat. A more recent study re-emphasized this point. In this 1-day study, 50,000 IU of vitamin D3 was given with a breakfast that was fat-free or which included fats. Mean peak vitamin D blood levels (12 hours after taking the supplement) were 32% greater in subjects who took the supplement with a fat-containing meal than in those who took it with the fat-free meal. The ratio of monounsaturated to polyunsaturated fats in the meal did not matter (Dawson-Hughes, J Acad Nutri and Dietetics 2014). The researchers postulate that the presence of fat favors vitamin D absorption by stimulating the secretion of bile which promotes fat absorption.

Concerns and Cautions:
Excessive intake of vitamin D as a supplement can potentially result in hypercalcemia (too much calcium in the blood) with symptoms including constipation, confusion, weakness, loss of appetite and painful calcium deposits. Although this is unlikely to occur when daily intake is under 10,000 IU, to avoid hypercalcemia and other potential problems associated with higher blood levels of vitamin D, keep total intake of vitamin D from supplements and food under the established Upper Tolerable Intake Level (UL) above which the risk of harm increases. The ULs are 1,000 IU for infants up to 6 months, 1,500 IU for infants 6 months to 12 months, 2,500 IU for children 1 to 3 years, 3,000 for children 4 to 8 years, and 4,000 IU for all other people.17 Note: It is not thought to be necessary to factor in the amount of vitamin D produced by sun exposure when adding up total vitamin D intake. 4,000 IU daily, given for 6 months to obese adolescents who were deficient in vitamin D, was found to be safe (no hypercalcemia) as well as effective at raising vitamin D to sufficient levels.26

A large study in Minnesota found that, due to increased use of vitamin D supplements, the percentage of people with vitamin D blood levels above 50 ng/mL increased 26-fold from 2002 to 2011, rising from 9 to 233 cases per 100,000 person-years; although hypercalcemia was rare among this group (0.2%), occurring only among those taking 50,000 IU weekly or more often. However, as noted in the study, levels above 50 ng/mL have not been found to be beneficial and pose potential long-term risks (Dudenkov, Mayo Clinic Proc 2015).

Giving high-dose vitamin D (96,000 to 120,000 IU) every two months has been shown to increase the risk of upper respiratory infections, compared to taking a low dose (400 IU) daily (Martineau, Thorax 2015)

High-dose vitamin D may decrease the natural production of melatonin (a mediator of sleep). A small, but well-controlled study in people with multiple sclerosis being treated with interferon found that, after 3 months, those also given high dose vitamin D3 (800 IU daily plus 75,000 IU every 3 weeks — averaging 4,370 IU per day) had a significant decrease in nighttime melatonin production, while those given a low dose (800 IU daily) did not. The study continued for full year during which vitamin D levels in the both groups fell (possibly due to shorter days of winter), and, melatonin product began to increase toward original levels (Golan, Brain, Behav, Immun 2013). Consistent with this, a study found that among overweight, postmenopausal women given 2,000 IU of vitamin D daily for 12 months, those whose vitamin D blood levels rose to over 32 ng/mL showed a modest deterioration of sleep quality (6.2% reduction) compared to those with blood levels that remained below 32 ng/mL (5.7% improvement). The deterioration in sleep quality -- as well an increased need for sleep medication -- was also associated with larger increases in vitamin D blood levels. Most women started study with vitamin D levels ranging from about 16 to 27 ng/mL and all participated in a weight loss/exercise program as part of the study (Mason, Preventive Medicine, 2016).

The FDA has cautioned that some liquid vitamin D supplements are sold with droppers that could allow for excessive dosing of vitamin D to infants. It recommends that droppers hold no more than 400 IU of vitamin D to avoid this problem.

It is particularly important to avoid excessive vitamin D during pregnancy, as hypercalcemia in a mother can lead to seizures, mental and/or physical retardation, and other problems in an infant.

Women taking a daily calcium (1,000 mg) and vitamin D (400 IU) supplement showed a 17% greater incidence of kidney stones compared to women who did not receive the supplement.22 The increased risk, however, is small, as only 0.35% of the women taking the calcium and vitamin D supplement reported kidney stones, compared to 0.30% of the women in the control group. A similar (17% to 20%) increase in kidney stones has been reported in studies with calcium supplementation alone, suggesting that calcium, rather than vitamin D, is the causative factor.

For more information see the articles about and calcium and vitamin D in the Natural Products Encyclopedia on this Web site. Also see the government report on vitamin D at http://ods.od.nih.gov/factsheets/vitamind.asp.


REFERENCES:
1 Fiscella, et al, Vitamin D, Race, and Cardiovascular Mortality: Findings From a National US Sample, Annals of Family Medicine, 2010; 8:11-18.

2 Armas, et al, Vitamin D2 is Much Less Effective than Vitamin D3 in Humans, The Journal of Clinical Endocrinology & Metabolism, 2004; 89(1):5387-5391.

3 Trang, et al, Evidence that vitamin D3 increases serum 25-hydroxyvitamin-D more efficiently than does vitamin D2, American Journal of Clinical Nutrition, 1998; 68:854-8.

4 Kumar, et al, Prevalence and Associations of 25-Hydroxyvitamin D Deficiency in US Children: NHANES 2001-2004, Pediatrics, 2009; 124(3):362-370.

5 Holick, et al, Vitamin D2 is as Effective as Vitamin D3 in Maintaining Circulating Concentrations of 25-Hydroxyvitamin D, J Clin Endocrinol Metab, March 2008, 93(3):677-681.

6 Hollis, B. W., Circulating 25-Hydroxyvitamin D Levels Indicative of Vitamin D Sufficiency: Implications for Establishing a New Effective Dietary Intake Recommendation for Vitamin D, J.

Nutri. 135:317-322, February 2005.

7 Biancuzzo, et al, Fortification of orange juice with vitamin D2 or vitamin D3 is as effective as an oral supplement in maintaining vitamin D status in adults, Am J Clin Nutr, April 28, 2010 (Epub ahead of print].

8 Vitamin D Consumer Fact Sheet, Office of Dietary Supplements, National Institutes of Health, Updated: 3/5/2010.

9 Milaneschi, et al, Serum 25-Hydroxyvitamin D and Depressive Symptoms in Older Women and Men, J. Clin Endocrinol Metab, May, 5 2010 [Epub ahead of print].

10 Sanders, et al, Annual High-Dose Oral Vitamin D and Falls and Fractures in Older Women, JAMA. 2010;303(18):1815-1822.

11 Dawson-Hughes, et al, High-Dose Vitamin D Supplementation: Too Much of a Good Thing? JAMA. 2010;303(18):1861-1862.

12 Terushkin, et al, Estimated equivalency of vitamin D production from natural sun exposure versus oral vitamin D supplementation across seasons at two US latitudes, J. Am Acad Dermatol 2010; 62(10), 929.e1-929.e9.

13 Llewellyn, et al, Vitamin D and Risk of Cognitive Decline in Elderly Persons, Arch Intern Med, July 12, 2010; 170(13):1135-1141.

14 Knekt, et al, Serum Vitamin D and the Risk of Parkinson Disease, Arch Neurol, July 2010; 67(7): 808-811.

15 Urashima, et al, Randomized Trial of Vitamin D Supplementation to Prevent Seasonal Influenza A in Schoolchildren, Am J Clin Nutr 2010; 91(5):1255-60.

16 Sandu, et al, The Role of Vitamin D in Asthma, Ann Allergy Asthma Immunol 2010; 105(3):191-199.

17 Dietary Reference Intakes for Calcium and Vitamin D (2010), Food and Nutrition Board, National Acadamies Press.

18 Ensrud, et al, Circulating 25-Hydroxyvitamin D Levels and Frailty Status in Older Women, J. Clin Endocrinol Metab, 2010 95: 5266-5273.

19 Sharief, at al, Vitamin D levels and food and environmental allergies in the United States: Results from the National Health and Nutrition Examination Survey 2005 - 2006, J. Allergy Clin Immunol, 2011 Published online February 17, 2011.

20 Green, et al, Calcium and vitamin-D supplementation on bone structural properties in peripubertal female identical twins: a randomised controlled trial, Osteoporosis Int 2011; 22(2):489-981.

21 Sun et al, Vitamin D intake and risk of cardiovascular disease in US men and women, Am J Clin Nutr. 2011 June 8 [Epub ahead of print].

22 Wallace, et al, Urinary tract stone occurrence in the Women's Health Initiative (WHI) randomized clinical trial of calcium and vitamin D supplements, Am J Clin Nutr 2011; 94: 5-6.

23 Mitri, et al, Vitamin D and type 2 diabetes: a systematic review, Eur J Clin Nutr, 2011, 1-11.

24 Bertone-Johnson, et al, Vitamin D intake from foods and supplements and depressive symptoms in a diverse population of older women, Am J Clin Nutr 2011 August 24 [Epub ahead of print].

25 Mulligan, Taking vitamin D with the largest meal improves absorption and results in higher serum levels of 25-hydroxyvitamin D, J Bone and Min Res 2010; 25(4): 928-930.

26 Belenchia, et al, Safety and efficacy of using high-dose (4,000 IU) vitamin D supplementation to improve the vitamin D status of obese adolescents, The FASEB Journal. 2011; 25:343.4., The FASEB Journal. 2011; 25:343.4

27 Wolpin, et al, Plasma 25-Hydroxyvitamin D and Risk of Pancreatic Cancer, Cancer Epidemiol Biomarkers Prev. 2011 Dec.7 [Epub ahead of print]

28 Amer, et al, Relation between serum 25-vitamin D and C-reactive protein in asymptomatic adults (from the continuous national health and nutrition examination survey 2001 to 2006), Am J Cardiol 2012 Jan.15 [Epub ahead of print], Am J Cardiol 2012 Jan.15[Epub ahead of print]

29 Lasco, et al (2012). Improvement of Primary Dysmenorrhea Caused by a Single Oral Dose of Vitamin D: Results of a Randomized, Double-blind, Placebo-Controlled Study. Arch Intern Med. 172(4):366-7.

30 Muir, et al (2011). Effect of vitamin D supplementation on muscle strength, gait and balance in older adults: a systematic review and meta-analysis, J Am Geriatr Soc. 59(12):2291-300.

31 Salehpour A, et al (2012). Vitamin D3 and the risk of CVD in overweight and obese women: a randomised controlled trial. Br J Nutr. Feb 9 2012 [Epub ahead of print]

32 Vacek, et al, Vitamin D Deficiency and Supplementation and Relation to Cardiovascular Health, Prev Cardio 2012; 109(3): 359—363.

33 Albanes, et al, Serum 25-Hydroxy Vitamin D and Prostate Cancer Risk in a Large Nested Case-Control Study, Canc Epidemiol Biomarkers Prev 2011; 20(9): 1850-1860.

34 Schwartz, G, Circulating Vitamin D and Risk of Prostate Cancer — Letter, Canc Epidemiol Biomarkers Prev 2012; 21(1): 246.

35 Durup, et al, A Reverse J-Shaped Association of All-Cause Mortality with Serum 25-Hydroxyvitamin D in General Practice, the CopD Study, J Clin Endocrinol Metab, August 2012 [Epub ahead of print]

36 Rejnmark, et al, Vitamin D with Calcium Reduces Mortality: Patient Level Pooled Analysis of 70,528 Patients from Eight Major Vitamin D Trials, J Clin Endocrinol Metab, August 2012 [Epub ahead of print]

37 LeBlanc, et al, Associations Between 25-Hydroxyvitamin D and Weight Gain in Elderly Women, Journal of Women's Health, June 2012 [Epub ahead of print]

38 Holmes, et al, Analytical Performance Characteristics of Two New Automated Immunoassays for 25 Hydroxy Vitamin D, Endocrine Soc. 2012 Meeting, (Poster presentation)

39 Bischoff-Ferrari, et al, A Pooled Analysis of Vitamin D Dose Requirements for Fracture Prevention, N Engl J Med; 367:40-9.

40 Logan, et al, Long-term vitamin D3 supplementation is more effective than vitamin D2 in maintaining serum 25-hydroxyvitamin D status over the winter months, Br J Nutr, July 2012 [Epub ahead of print]

41 Kabadi et al. Joint Effects of Obesity and Vitamin D Insufficiency on Insulin Resistance and Type 2 Diabetes: Results from the NHANES 2001-2006. Diabetes Care, 2012 [Epub ahead of print]

42 Coussens, et al, Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment, PNAS, September 4, 2012 [Epub ahead of print]

43 Annweiler, et al, Higher Vitamin D Dietary Intake Is Associated With Lower Risk of Alzheimer's Disease: A 7-Year Follow-up, J Gerontol A Biol Sci Med, April 2012 [Epub ahead of print]

Information on this site is provided for informational purposes only. It is not an endorsement of any product nor is it meant to substitute for the advice provided by physicians or other healthcare professionals. The information contained herein should not be used for diagnosing or treating a health problem or disease. Consumers should inform their healthcare providers of the dietary supplements they take.
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