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Optimum Vitamin D level: Evidence for 30 and 40 ng – Grant Aug 2013

Evidence that the minimum optimal serum 25(OH)D concentration is 30 ng/ml (or 40 ng/ml)

November 16, 2012; Revised April 3, 2013; August 16, 2013

William B. Grant, Ph.D.
Sunlight, Nutrition, and Health Research Center
P.O. Box 641603
San Francisco, CA 94164-1603, USA
www.sunarc.org, wbgrant at infionline.net


From my review of the journal literature, 30 ng/ml is the minimum 25(OH)D concentration associated with optimal health. This value has been reported for pregnancy outcomes, breast cancer in case-control studies, colorectal cancer in case-control and cohort studies, cardiovascular disease, all-cause mortality rate, and agreed to in several reviews [Bischoff-Ferrari, 2006, 2008; Holick, 2011; Miller, 2011; Pérez-López, 2012; Souberbielle, 2010; Vieth, 2011].

The Institute of Medicine recommended 20 ng/ml in part since they accepted only randomized controlled trials (RCTs), and then, only for fractures [Ross, 2011]. They were using the tenets of “evidence based medicine”, which puts meta-analyses of RCTs as the strongest evidence. That approach may or may not be appropriate for pharmaceutical drugs [Biesalski et al., 2011; Hickey and Roberts, 2011], but is not appropriate for vitamin D, which is not a drug but a molecule largely derived from the interaction of solar ultraviolet-B (UVB) irradiance on 7-dehydrocholesterol in the skin. Thus, observational and ecological studies can provide much of the evidence.

One of the problems with nested case-control studies with long follow-up times is that serum 25(OH)D concentration changes with time, so the longer the follow-up time, the lower the beneficial effect found for 25(OH)D as I’ve demonstrated in two recent papers [Grant, 2011a, 2012a].

A problem with cross-sectional studies is that the disease state may influence the serum 25(OH)D concentration, for example, by making the person more likely to stay indoors.

The papers listed below provide some of the evidence, based primarily on observational studies with some cross-sectional studies and RCTs, for the minimum optimal serum 25(OH)D concentration is 30 ng/ml:

  • Arterial calcification [Naves-Diaz, 2013]
  • Asthma severity [Majak, 2012]
  • Athletic performance [Larson-Meyer, 2010, 2013; Udowenko, 2010]
  • Blood pressure [Larsen, 2012]
  • Bones, fractures [Bonnot, 2011; Carmel, 2012; Dawson-Hughes, 2012; Rizzoli, 2013; von Domarus, 2011]
  • Breast cancer from case-control studies [Abbas, 2008, 2008; Bilinski and Boyages, 2012; Crew, 2009; Fedirko, 2012; Grant, 2010, 2012b; Lowe, 2005]
  • Breast cancer survival [Bauer, 2013; Hatse, 2012; Tretli, 2012]
  • Cardiovascular disease [Anderson, 2010; Brøndum-Jacobsen, 2012; Kim, 2008; Liu, 2012; Riek, 2012; Vacek, 2012; Wang, 2012]
  • Cognitive decline [Slinin, 2012; Soni, 2012]
  • Colorectal cancer from case-control and cohort studies [Grant, 2010]
  • Cystic fibrosis [Tangpricha, 2012]
  • Dental caries [Grant, 2012; Schroth, 2012]
  • Diabetes mellitus [González-Molero, 2012; Pittas, 2012]
  • Function [Sohl, 2013]
  • Immune status [Dixon, 2012]
  • Insulin resistance [Heaney, 2013; Kelly, 2011; von Hurst, 2010]
  • Metabolic syndrome [Pacifico, 2011]
  • Mobility limitation, disability [Houston, 2012]
  • Mortality rate, all-cause [Schöttker, 2013; Signorello, 2012; Zittermann, 2012; ]
  • Multiple sclerosis [Holmøy, 2012]
  • Osteoarthritis of the hip [Chaganti, 2010]
  • Physical performance [Wicherts, 2007]
  • Pregnancy outcomes [Bodnar, 2007, 2009, 2010, 2013; Merewood, 2007; Principi, 2012; Whitehouse, 2012]
  • Quality of life [Ecemis, 2013]
  • Respiratory infections [Ginde, 2009; Science, 2013]
  • Review [Battault, 2012; Bischoff-Ferrari, 2010; Holick, 2011; Hossein-Nezhad, 2013; Pludowski, 2013; Souberbielle, 2010]
  • Tuberculosis [Nnoaham, 2008]

There is also evidence for beneficial effects near or above 40 ng/ml

  • Athletic performance [Larson-Meyer, 2013]
  • Bones [Binkley, 2012; Prieto-Alhambra, 2012]
  • Cancer [Lappe, 2007]
  • Chronic kidney disease [Kramer, 2012]
  • Crohn’s disease [Yang, 2013]
  • Depression [Jaddou, 2012]
  • Infections, hospital [Quraishi, 2013]
  • Multiple sclerosis [Pierrot-Deseilligny, 2012]
  • PTH [Lu, 2012; Valcour, 2012]
  • Pregnancy [Hollis, 2011; Hollis and Wagner, 2011; Morales, 2012]
  • Respiratory infections, acute [Sabetta, 2010]
  • Review [Grant, 2011b]
  • Systemic lupus erythematosus [Petri, 2013]

There are few data for health outcomes above 50 ng/ml.

The U-shaped 25(OH)D concentration-health outcomes showing generally do not report statistically significant findings. Other such findings are not supported by other studies for the same outcome, such as pancreatic and prostate cancer. There is one recent study from Denmark showing a J-shaped serum 25(OH)D concentration-all-cause mortality rate relation [Durup, 2012]. In my opinion, that finding was due to older people being informed that they had a vitamin D deficiency, perhaps due to a diagnosis of osteoporosis, and being advised to take vitamin D supplements. In support of this hypothesis, I note that two studies of frailty among elderly Americans determined four years after serum 25(OH)D concentration measurement found a linear inverse relation between frailty status and serum 25(OH)D concentration for men [Ensrud, 2011] but a U-shaped relation for women [Ensrud, 2010]. In the United States, women are much more likely to be diagnosed with osteoporosis and then be told to take vitamin D supplements than are men. As mentioned by Dr. Hypponen, there does not appear to be a mechanism to explain why serum 25(OH)D concentrations between, say, 50 ng/ml and 100 ng/ml, should be associated with increased risk of disease.

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