Thursday, December 20, 2012

What's the Optimal Dose of Vitamin D3 for Lean, Normal-, Overweight & Obese Women With Established Vitamin D Deficiency to Get 25OHD Back into the Normal Range?

Both ladies are D-ficient, but will probably need profoundly different amounts of D3 to get their 25OHD back in range.
Actually, I guess, I don't really have to tell you that there is not going to be guest post by Adelfo Cerame, today. Adelfo is busy with the last weeks of school, but will be back as soon as he has passed all the tests. And while I am not sure, whether or not you would call the latest on vitamin D supplementation an adequate replacement for a contest prep update from "your's truly", I suppose that it's better than nothing to bridge the time that still remains until the SuppVersity  Science Round-Up on the Super Human Radio Network is going to air (the show starts at 12PM, EST; the Science-Round-Up airs in the 2nd hour and will thus begin at 1PM, EST; click here to listen live or wait for the podcast // update: now available).

I am honestly not yet sure what exactly we will cover today, but among the things I am still thinking about how we can squeeze them into a 1h show are...
  • methylxanthines caffeine, theobromine and theophylline can bind to human DNA - what does that tell us about the purported health benefits of caffeine & co?
  • caffeine prevents memory impairment - in this case in a model of sporadic Alzheimer's disease
  • anti-Alzheimer's effect of CLA - plus a list of supplements that have been implicated in the prevention of Alzheimer's and other amyloid diseases such as Parkinson's, Cerebellar Ataxis, Amyotrophic lateral sclerosis and (hardly recognized as an amyloid disease) diabetes type II
  • the effect of body weight on the benefits of circuit training in older women - turns out that those who need it the most, namely the obese, also see the greatest benefits
  • Gum arabicum to ward off holiday weight gain - that this could actually work is at least what a recent human study would suggest
  • more on vitamin E, resveratrol, soldiers don't get hurt in battle, but by geranium (DMAA), ...
I think there should be something for everyone of you. Plus: If everything works out, this is going to be the first show to air live via Skype, so no nagging land line echoes and noise any more.

Let's get to the D-news, now

The general consensus among the vitamin D advocates currently is that 2,000 IU of vitamin D3/day is the minimum you need to bring low levels of 25OHD back into the normal range. A soon-to-be-published study by Gallagher, Yalamanchili and Smith that's available ahead of print on the website of the Journal of Steroid Biochemistry and Molecular Biology does yet contradict this notion - at least for women with a body mass <25kg/m² even the meager RDA of 400IU would be enough (Gallagher. 2012). That said the concise paper actually describes the results of two, not just one experiment, with
  • study 1 (ViDOS) being a one-year randomized, double-blind placebo controlled study (ViDOS – Vitamin D supplementation in Older Subjects) of increasing doses of vitamin D3 (400,  800, 1600, 2400, 3200, 4000 or 4800 IU/day vitamin D3 vs. placebo + calcium supplements to maintain calcium intake between 1,200-1,400mg/day) in 163 Caucasians, age 57–90 years; all vitamin D insuf´Čücienty, i.e. serum 25OHD ≤ 20 ng/ml (50 nmol/l), and 
  • study 2 (STOP IT) being a 3-year intervention study of calcitriol 0.25 mcg (the active form of vitamin D) twice daily, conjugated estrogens 0.625 mg  daily, a combination of both and placebo in 488 elderly women, age 65–77 years
Body composition indices for the studies at hand (i.e. percentages of total and regional fat and fat-free mass) were measured by dual energy X-ray absorptiometry (DEXA Hologic Delphi) at baseline and after 12 months.
Figure 1: Mean total body weight, total body lean mass, total body fat mass and serum 25OHD in different BMI subgroups of study 2 (STOPIT); right, corresponding calculated ratios (based on Gallagher. 2012).
Even the baseline data in figure 1 does actually yield some insights into the relation of BMI, adiposity and 25OHD levels. While the data on the left already shows that the fat mass increases almost linearly across the BMI levels, while the lean mass remains relatively stable (with the highest value in the overweight group, though), the ratios I calculated and plotted on the right-hand side of figure 1 make it even more obvious clear: The lean / fat mass ratio scales with the BMI. With identical levels in the normal- and overweight individuals and significant increases and declines in the lightest and heaviest study participants. Moreover, the 25OHD vitamin D to fat mass ratio drops most significantly between the low BMI and the upper normal zone, where I suppose even most of the "healthy" individuals will be hovering around these days.

Being lean is a positive predictor of increases in 25OHD with supplementation

That this latent "chubbiness" of the average Westerner may be of particular significance in view of the negative / non-significant outcomes in many of the vitamin D supplementation trials, becomes self-evident, when you take a closer look at the data in figure 2, however you will have to realize that my plot which comprises above all the highly relevant relative changes (middle, marked in red) tells a different story than the original plot from the study showing only the absolute changes (left, but in form of a line graph).
Absolute, relative (compared to baseline) changes and total 25OHD levels (ng/ml) after supplementation with low, medium and high amounts of vitamin D3 in lean, normal, overweight and obese women (based on Gallagher. 2012)
Accordingly, the conclusion of the abstract, which says that "the response to vitamin D is dependent on body weight" and that "women with BMI <25 kg/m² develop much higher levels of serum 25OHD after vitamin D supplementation compared to those with BMI of >25 kg/m²" (Gallagher. 2012) may be correct, but is somewhat misleading as it is open to be interpreted as 'lean women respond most favorably to vitamin D supplementation' - an interpretation that is not really sustainable in view of the relative changes I calculated for figure 2  (middle), yet by no means as incredible as the abstract of another vitamin D study, I dessicated back in September (see "Stronger & Leaner or Fatter & Less Muscular W/ 4,000IU Vitamin D3 - What if Abstract and Data Tell Different Stories?")

Bottom line: The data from this most recent investigation into the differential response of lean, normal, overweight and obese women to vitamin D3 supplementation shows that the absolute increases appear on BMI and that...
  • Always take vitamin D with fatty foods! (see "A Fat D-Ficiency")
    low dose supplementation (400 or 800IU/day) is probably only sufficient to rise and maintain adequate vitamin D levels in lean women,
  • medium dose supplementation (1,400 or 2,400IU/day) yields the most favorable outcomes in total 25OHD levels and 
  • high dose supplementation (3,200, 4,000 or 4,800IU/day) does not yield additional benefits in either the the normal-, overweight and obese subgroup and only marginally higher levels in the lean women.
Overall the study at hand would thus support the notion that a daily vitamin D supplement containing ~2,000IU is the best way to get deficient levels back up, esp. for lean women it should be no problem to cut back to 2x the RDA, i.e. 800IU after normal vitamin D levels are achieved. For the rest, future studies will have to show if low dose supplementation is enough.

These longissimus dorsi slices of mice on a normal and a vitamin D3 supplemented diet show that supplemental vitamin D3 can be used as a fat synthesizer and meat tenderizer in "meat-producing animals". (learn more)
The often-heard hypothesis that the decreased response to vitamin D supplementation in the obese would be a result of the preferential storage of vitamin D in the adipose tissue was not supported by data of the Ghallagher study "there is no evidence from the dose response curves that in obesity serum 25OHD is being deposited in fat" (Gallagher. 2012). In view of the fact that contrary to total vitamin D, which is in fact preferentially stored in adipose tissue (78%) over lean muscle (14%), 25OHD stores are distributed much more evenly with 33% being stored in body fat and 20% in muscle tissue in omnivores like humans and swine (the data is in fact based on a study in pigs; cf. Jakobsen. 2007).

Lastly, a beneficial effect of increase / normalized vitamin D levels on lean or fat mass was (once again) not observed in any of the studies; and that despite the fact that "body fat was an independent predictor of serum PTH", which decreased in response to calcitriol supplementation in study 2 (which is actually more of an adjunct for correlative analysis and as a data source to compare the results of study 1 to). In other words, normalizing your vitamin D levels without taking appropriate measures to counter what's probably behind both, the nasty body fat and the low vitamin D level is not going to make you lean or musclar - at least as of now, it rather appears as if this was yet another instance, where we are - if anything - treating isolated symptoms instead of the root causes of the obesity epidemic.

References
  • Gallagher JC, Yalamanchili V, Smith LM. The Effect Of Vitamin D Supplementation On Serum 25OHD In Thin And Obese Women. J Steroid Biochem Mol Biol. 2012 Dec 11.
  • Jakobsen H, Maribo A, Bysted HM, Sommer OH. 25-Hydroxyvitamin D3 affects vitamin D status similar to vitamin D3 in pigs – but the meat produced has a lower content of vitamin D. British Journal of Nutrition. 2007; 98 908–913.
  • Shephard RJ. Limits to the measurement of habitual physical activity by questionnaires. Br J Sports Med. 2003 Jun;37(3):197-206; discussion 206.