Hypothesizing an explanation for vitamin D's wide-ranging protective effects, the authors noted vitamin D's ability to inhibit the proliferation of cancer cells, improve blood vessel function and boost immunity. They also suggest that statin drugs' ability "to decrease all-cause mortality could partly be due to increases in vitamin D levels they would provoke or through acting as vitamin D analogues on vitamin D receptors."

In an accompanying editorial, Edward Giovannucci, MD, ScD, of the Harvard School of Public Health questioned: "Would even a greater reduction in mortality accrue than that suggested in this meta-analysis if intakes of vitamin D were higher, if compliance was improved, if higher levels of 25-hydroxyvitamin D [vitamin D3] were attained, and if the duration of supplementation was longer?"

"From a broader public health perspective, the roles of moderate sun exposure, food fortification with vitamin D, and higher-dose vitamin D supplements for adults need to be debated," Giovannucci urged.

While scientists debate, one thing is clear: ensuring intake of vitamin D in amounts sufficient to produce blood levels in the range of 70-80 nmol/L, which research now indicates should be around 2,000 IU of vitamin D3 per day, helps protect against all causes of death.

Autier P, Gandini S. Vitamin D Supplementation and Total Mortality: A Meta-analysis of Randomized Controlled Trials. Arch Intern Med. 2007 Sep 10;167(16):1730-7.
Abstract

Giovannucci E. Can vitamin d reduce total mortality? Arch Intern Med. 2007 Sep 10;167(16):1709-10.
Abstract

Vitamin D Supplements May Lower Mortality Rates

The September 10, 2007 issue of Archives of Internal Medicine reported the results of a meta-analysis that examined 18 previously published studies which had suggested that deficiencies in vitamin D lead to a higher risk of death from cancer, heart disease and diabetes.

The report stated that those individuals isolated from the studies who took vitamin D supplements had a seven percent lower risk of death than those who did not take supplements.

"If the associations made between vitamin D and these conditions were consistent, then interventions effectively strengthening vitamin D status should result in reduced total mortality," wrote the researchers from the International Agency for Research on Cancer in France and from the European Institute of Oncology in Italy.

The meta-analysis looked at randomized controlled trials of vitamin D supplements published before November 2006. They found and analyzed 18 separate trials involving 57,311 individuals.

The average vitamin D dose was 528 iu (international units), but ranged from 300 to 2,000 iu. Commercially available vitamin D supplements typically range from 400 to 600 iu.

Over a follow-up period of 5.7 years, 4,777 of the participants died. In the nine trials that had collected blood samples, those individuals who took vitamin D supplements had an average of between 1.4 and 5.2 times higher blood levels of vitamin D than those who didn’t.

“In conclusion, the intake of ordinary doses of vitamin D supplements seems to be associated with decreases in total mortality rates,” said the authors.

However, the relationship between vitamin D status and supplementation remains to be fully understood and the authors are calling for additional population-based, placebo-controlled randomized trials to further investigate their findings.

“Mechanisms by which vitamin D supplementation would decrease all-cause mortality are not clear,” said the researchers.

It is widely known that vitamin D deficiency can lead to osteoporosis, osteopenia, muscle weakness, fractures, common cancers, infectious diseases, autoimmune diseases, and cardiovascular diseases.

Median adult intake of vitamin D in the US is said to be only 230 iu per day, much lower than what nutrition experts have said should instead be 2,000 iu per day.

Autier, Philippe and Sara Gandini. "Vitamin D Supplementation and Total Mortality: A Meta-analysis of Randomized Controlled Trials." Arch Intern Med. 2007;167:1730-1737.
Abstract

Optimal Vitamin D Levels Protective Against Colorectal Cancer

Previous studies, including the Women's Health Initiative, found that a low dose of vitamin D (400 iu/day) was not protective against colorectal cancer, but new research shows that vitamin D offers significant protection when taken at a higher dose (1,000 – 2,000 iu/day).

The new research reviewed 5 studies involving a total of 2,896 subjects. Study participants with blood levels of D3 of at least 33 ng/mL (nanograms per mililiter)—the equivalent of 82.5 nmol/l (nanomoles per liter) were found to have a 50% lower risk of colorectal cancer compared to those whose blood levels of D3 were 12 ng/mL (30 nmol/l) or less.

The authors of this review recommend a daily intake of 2,000 iu/day of vitamin D3 to reduce incidence of colorectal cancer with minimal risk. This supports their recommendation by referring to an analysis of 30 studies, that found no reproducible toxicity when blood levels of D3 were below 100 ng/mL (250 nmol/l).

In addition, a “No Adverse Effect Level” (NoAEL) level of 2,000 iu/day of vitamin D3 has been established by the National Academy of Sciences (NAS). The NAS reported that no illness from vitamin D intoxication has been described for intakes <3,800 iu/day. One study reported that no cases of toxicity have ever been documented at doses <40,000 iu per day.

A vitamin D3 intake of 1,000–2,000 iu/day, with a target of 33 ng/mL (82.5 nmol) for blood levels of D3 are safe, practical recommendations to reduce risk of colon cancer.

Gorham ED, Garland CF, Garland FC, Grant WB, Mohr SB, Lipkin M, Newmark HL, Giovannucci E, Wei M, Holick MF. Optimal vitamin D status for colorectal cancer prevention: a quantitative meta analysis. Am J Prev Med. 2007 Mar;32(3):210-6.
Abstract

Vitamin D – Protective Against Breast Cancer

A review of two studies involving 1,760 women found that those who had blood levels of vitamin D3 of at least 52 ng/ml (the equivalent of 130 nmol/l) had a 50% lower risk of breast cancer than those whose blood levels of D3 were <13 ng/ml (32.5 nmol).

Since a vitamin D3 blood level of 52 ng/ml (130 nmol/l) would necessitate an intake of 4,000 iu of D3 daily, which exceeds the National Academy of Sciences upper limit of 2,000 iu per day, the researchers recommend supplementing with 2,000 iu/day plus 12 minutes of sun exposure.

Moderate exposure to sunlight (about 12 minutes during late spring, summer and early fall in northern latitudes [above 51º] or throughout the year in southern latitudes [below 35º]) is thought to produce an amount of D3 equivalent to supplementing with 3,000 iu.

Women who are at high risk for breast cancer and who live in northern latitudes may wish to talk to their health care provider about supplementation with doses higher than 2,000 iu/day of vitamin D3 during the winter.

Garland CF, Gorham ED, Mohr SB, Grant WB, Giovannucci EL, Lipkin M, Newmark H, Holick MF, Garland FC. Vitamin D and prevention of breast cancer: pooled analysis. J Steroid Biochem Mol Biol. 2007 Mar;103(3-5):708-11.
Abstract

Insufficient Vitamin D – the Principal Cause of Preeclampsia

In preeclampsia, the most common, dangerous complication of pregnancy, blood pressure rises along with the appearance of significant amounts of protein in the urine. The condition can cause significant damage to the blood vessels, kidneys and liver of the mother, and has no known cure apart from ending the pregnancy.

A recent study involving 1,198 women in their first pregnancy has shown that vitamin D deficiency is a strong, independent risk factor for preeclampsia.

Women with low blood levels of vitamin D (>45.4 nmol/l) in early pregnancy were much more likely to develop preeclampsia than women whose vitamin D levels were higher (<53.1 nmol). Early pregnancy blood levels of vitamin D <37.5 nmol/l were associated with a 5-fold increase in risk of developing preeclampsia.

Babies born to mothers with preeclampsia were much more likely to be deficient in vitamin D, despite the widespread use of prenatal vitamins, which provide 400 iu of vitamin D.

On the positive side, as mothers' blood levels of vitamin D increased, their risk of pre-eclampsia strikingly decreased, as did their babies' risk of vitamin D deficiency.

A recent review study found that blood levels of vitamin D3 needed for bone mineral density, dental health, and to lessen risk of falls, fractures and colorectal cancer, begin at 75 nmol/l, and are best between 90 and 100 nmol/l. Many experts now recommend daily intake of 1,000 iu of vitamin D3 to bring blood levels up to 75 nmol/l.

Women who are pregnant or hoping to conceive should ask their doctor to check their blood levels of vitamin D3 and to consider supplementation (D3, 1,000 iu/day) if their blood levels are lower than 75 nmol/l.

Bodnar LM, Catov JM, Simhan HN, Holick MF, Powers RW, Roberts JM. Maternal vitamin D deficiency increases the risk of preeclampsia. : J Clin Endocrinol Metab. 2007 May 29; [Epub ahead of print]
Abstract

Vitamin D Levels Affect Cardiovascular Risk

Low blood levels of vitamin D are strongly associated with risk factors for cardiovascular disease, reveals data on 7,186 men and 7,902 women from the Third National Health and Nutrition Examination Survey. (Martins D, Wolf M, Arch Intern Med 2007 June)

Vitamin D refers to two biologically active precursors: D2, which is known as ergocalciferol and is derived from foods such as fatty fish, egg yolk and liver, and D3, cholecalciferol, which is produced in the skin upon exposure to sunlight. Both D2 and D3 are processed in the liver and kidneys to form 25(OH)D, the "storage" form in which vitamin D circulates in the bloodstream.

Compared to higher blood levels of this storage form of vitamin D, 25(OH)D, (at least 37 ng/mL [92 nmol/L]), low levels (less than 21 ng/mL [52 nmol/L]) were associated with greatly increased odds of:

• Hypertension (130% or 1 ? times the risk)
• Diabetes mellitus (198%, double the risk)
• Obesity (229% or 2 ? times the risk)
• High triglycerides (147%, 1½ times the risk)

According to researchers, this study indicates it is time to reassess the current position on the levels of vitamin D considered adequate and optimal. Current recommended blood levels of vitamin D [25(OH)D] are primarily based on levels needed to maintain bone health and prevent rickets, but do not address the levels necessary to minimize cardiovascular risk factors.

Since prevalence of CVD risk factors continued to decline as vitamin D levels reached and surpassed 37 ng/mL (92 nmol/L), researchers think higher levels may confer additional benefits.

Prevalence of Insufficient Vitamin D Levels “Alarmingly High”

In the UK, British researchers measured vitamin D levels in 7,437 adults over age 45 and found the prevalence of low levels of vitamin D “alarmingly high.”

In winter and spring, 87.1% of subjects had vitamin D levels less than 75 nmol/L (30 ng/mL). Even during the summer and fall, vitamin D levels in 60.9% of subjects were below 75 nmol/L (30 ng/mL). Low vitamin D levels (<40 nmol/L or 16 ng/mL) were twice as likely in obese subjects. (Hyppönen E, Power C., Am J Clin Nutr 2007 March)

Daily Dosage Recommendations for Vitamin D Should Be Greatly Increased

Researchers who conducted a review of numerous well-designed human clinical trials published since 1997 feel that the upper tolerable limit (UL) of 2,000 iu per day set for vitamin D by the Food and Nutrition Board at that time, is way too low and should be increased five-fold.

They are confident that, in healthy adults, even a dose of vitamin D3, the most biologically active form of the vitamin, of up to 10,000 iu per day can be safely recommended. (Hathcock JN, Shao A. et al. Am J Clin Nutr 2007 Jan)

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