Saturday, May 17, 2014

Based on the Latest Evidence, Who Would Benefit From Even more Vitamin D? Plus: How Much Vitamin D Do I Need To Achieve Optimal Levels & Keep Them Steady?

Injecting large doses of vitamin D is unnecessary to get into the normal range and everything way above 35ng/ml could be doing more harm than good.
It's not as hot as it's use to be, but the token "vitamin" will still produce mostly studies dealing with "vitamin D", when you type it into the search field of PubMed or any other medical database search. Against that background, it's almost pathetic that "information regarding the associations between vitamin D and inflammatory markers in the general population is sparse" (Hannemann. 2014) - we know the non-classical effects of vitamin D on the innate and adaptive immunity for 30 years and still, at least for Germany only few studies assessed the relation between vitamin D and chronic inflammation in a way that would allow us to answer the question I posed in the title of today's SuppVersity article.
You can learn more about vitamin D at the SuppVersity

Vitamin D Builds Muscle

Leucine, Insulin & Vitamin D

Vit. D Speeds Up Recovery

Overlooked D-Sources

Vitamin D For Athletes!

Vitamin D Helps Store Fat
In their latest paper in the peer-revied scientific journal Metabolism, Liesa Mellenthin, Henri Wallaschofski, Anne Grotevendt, Henry Völzke, Matthias Nauck, and Anke Hannemann from the University of Greifwald present the corresponding data. Data from 2723 men and women aged 25-88
years who were part of the first follow-up of the Study of Health in Pomerania.
Figure 1: Vitamin D status of the 2723 men and women in the Study of Health in Pomerania (Mellenthin. 2014)
As you can see in Figure 1 the number of Germans with low vitamin D levels is significant. The number of subjects in the target range of >30ng/ml 25OHD, on the other hand, was comparatively low.

The selected few are at a disadvantage

Interestingly, those "selected few" who are "in the zone", were  not the ones with the lowest levels of hs-CRP, the contemporary standard marker of whole body inflammation.
Vitamin D statusHs-CRPFibrinogenWhite blood cell count

Deficiency (n = 322)1.40 (0.88-2.22)ReferenceReferenceReference
Insufficiency (n = 1301)1.27 (0.91-1.78)0.75 (0.51-1.09)0.92 (0.52-1.61)0.69 (0.39-1.22)
Sufficiency (n = 744)Reference0.69 (0.44-1.06)0.59 (0.29-1.17)0.79 (0.43-1.45)
Target Range (n = 356)1.18 (0.72-1.95)0.50 (0.28-0.91)0.57 (0.24-1.35)0.51 (0.24-1.11)
Table 1: Odds ratios (OR) and 95% confidence intervals (CI) from multivariable logistic regression models for the association between vitamin D status with increased inflammatory biomarker concentrations (≥90 th percentile)
Whether the lower white blood cell counts above the target range are desirable may depend on whether you're suffering from an auto-immune disease. In general, they are yet another reason to keep the in mind that Mellenthin et al. are not the first to observe a non-linear, U-shaped dose-response relationship for the beneficial health effects of vitamin D.
There are exceptions to all "rules" - except from one: Testing makes sense, because low levels of 24OHD are far worse than high ones! Whether or not 25OHD levels way beyond the sufficiency range of 30ng/ml (75mmol/l) will promote or impair your health will depend on many factors. Autoimmune diseases, as mentioned before, may be one. In view of the fact that most 99% of the reported benefits were observed in subjects with insufficient, if not deficient pre- (at the beginning of the experiment) vitamin D levels, even these alleged benefits are in no way certain. I mean, look at the data in Figure 2 (right). Even in otherwise healthy people it's way better to have slightly high D levels than extremely low ones. In the end, the best way to make sure you are doing fine is to test: As long as you hover in the 28-40ng/ml range yearlong, there is nothing to freak out about.
In this case this was a reduction in overall inflammation. In previous studies similar U-shaped, non-linear dose-response relationships were observed for
  • Did you know? Seasonal variation in serum 25(OH)D is between 10 and 20 nmol/L. Sunscreen use decreases, but does not abolish, vitamin D production in the skin. A high dietary calcium intake has a vitamin D-sparing effect, because it increases the half-life of 25(OH)D. A combination of sunlight exposure, nutrition, food fortification, and supplements is desirable to obtain sufficient vitamin D status in the population of most countries throughout the year (Lips. 2014).
    pre-hospital vitamin D status and mortality in a recent paper in the Journal of Clinical Endocrinology & Metabolism (Amerin. 2014),
  • serum 25‐Hydroxyvitamin D and fracture risk in older men in the Prospective Population Based CHAMP Study (Bleicher. 2014),
  • the maternal and newborn vitamin D status and its impact on food allergy development in the German LINA cohort study (Weisse. 2013)
  • the population-wide cancer risk (White. 2013)
  • the duration of hospital stays after cardiac surgery (Zittermann. 2013), 
  • the association between vitamin D & mortality and morbidity based on data for 1 282 822 Clalit Health Services members aged >45 between July 2007 and December 2011 (Dror. 2013)
I could extent this list endlessly, but I honestly have better things to do, so let's stick to that and say: The notion that "more vitamin D" equals better health is obviously more than questionable. 
Figure 2: 25OHD levels and survival (left) and calculated risk for (right) of increased mortality in 1 282 822 Clalit Health Services members aged >45 between July 2007 and December 2011 (Dror. 2013)
Needless to say you are better off in the high 25OHD region (Figure 2, right >28-32), but if your goal is to avoid dying within the next 60 months, the previously cited study by Dror is only one of many references that would suggest that you are better of in the happy medium.
Studies like Close et al. (2013) leave little doubt that it does not take tons of vitamin D to get lowish levels back into the normal range - in fact, taking too much, in this case 40,000 IU per week, will take you into a 25OHD range, where the benefits are starting to diminish. Still, even here you're better off than you'd be with "officially low" 25OHD levels of <25ng/ml.
Bottom line: Vitamin D does not break the "more is not more"-rule of medical sciences. Instead of thriving to bring your vitamin D levels up into the hilarious D-council levels, you'd do yourself or rather your overall health a favor if you  hovered around in the normal zone.
This does not mean that you should try to avoid being deficient at all costs. So, how much do you need? Well, assuming that most of you are young(er) and active, you can follow the same protocol as the young healthy men in a 6-week trial by Close et al. whose previously low levels jumped up to >30 ng/ml was only 20 000 IU per week (for older subjects and/or subjects with (pre-)diabetes / other chronic disease with inflammatory component, twice the dosage may be necessary; cf.  Davidson. 2014).
A means to ensure sufficiency for the misers who are to cheap to test, would thus be taking 5,000IU every day for 1 month and a maintenance dose of 1,000IU/day or 10,000IU once per week to maintain optimal levels (Is it better to take your D and other fat soluble vitamins w/ fat? learn more) .
  • Amrein, Karin, et al. "Evidence for a U-shaped relationship between pre-hospital vitamin D status and mortality: a cohort study." The Journal of Clinical Endocrinology & Metabolism (2014).
  • Bleicher, Kerrin, et al. "U‐Shaped Association Between Serum 25‐Hydroxyvitamin D and Fracture Risk in Older Men: Results from the Prospective Population Based CHAMP Study." Journal of Bone and Mineral Research (2014).
  • Close, Graeme L., et al. "The effects of vitamin D3 supplementation on serum total 25 [OH] D concentration and physical performance: a randomised dose–response study." British journal of sports medicine 47.11 (2013): 692-696. 
  • Davidson, Mayer B., et al. "High-dose vitamin D supplementation in people with prediabetes and hypovitaminosis D." Diabetes Care 36.2 (2013): 260-266.
  • Dror, Yosef, et al. "Vitamin D levels for preventing acute coronary syndrome and mortality: evidence of a nonlinear association." The Journal of Clinical Endocrinology & Metabolism 98.5 (2013): 2160-2167.
  • Mellenthin, Liesa, et al. "Association Between Serum Vitamin D Concentrations and Inflammatory Markers in the General Adult Population." Metabolism (2014).
  • Lips P, van Schoor NM, de Jongh RT. "Diet, sun, and lifestyle as determinants of vitamin D status." Ann N Y Acad Sci. (2014).
  • Weisse, K., et al. "Maternal and newborn vitamin D status and its impact on food allergy development in the German LINA cohort study." Allergy 68.2 (2013): 220-228.
  • White, John H. "Vitamin D and human health: more than just bone." Nature Reviews Endocrinology 9.10 (2013): 623-623.
  • Zittermann, Armin, et al. "Vitamin D status and the risk of major adverse cardiac and cerebrovascular events in cardiac surgery." European heart journal 34.18 (2013): 1358-1364.