Wednesday, August 17, 2011

Vitamin D & PUFA - Is There an Overlooked Antagonism Between Polyunsaturated Fatty Acids and Vitamin D3?

Image 1: Do not write off all the "good"
foods until you read the full blogpost,
including my comment at the end
(image by ADAM)
Hah... I knew a newsitem the title of which joins everybody's contemporary "pet supplements", would get your attention. Quasi as a byproduct of one of the hilarious vitamin D + calcium trials in which scientists seek to prevent bone loss and fracture in men and women age 65 and older by supplementation with 700IU (no I am not missing a "0", here) and 500mg calcium per day, Sathi Niramitmahapanya and his colleagues from the  U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University found an interesting and previously not thought of negative correlation between their subjects' plasma levels of 25-hydroxyvitamin D (25OHD) levels and the ratio of poly- to monounsaturated fatty acids in their diets (Niramitmahapany. 2011). Could it be that you have to choose, when it comes to high vitamin D or PUFA intake?

Since this was not a specifically designed experiment, Niramitmahapany et al. had to rely on the data that had already been gathered in a 3-year, randomized, double-blind, placebo-controlled trial, originally designed to determine the effect of supplemental vitamin D + calcium on rates of  bone loss and fractures in 152 men and women (age >65years). Consequently, the study relies heavily on the accuracy of complex regression analysis, by the means of which the Tuft researchers tried to figure out which of the handful of confounding variables they had surveyed, had the greatest influence, or I should say statistically measurable explanatory value for the effect of vitamin D3 supplementation on serum 25-hydroxyvitamin D levels in their elderly subjects.
In essence a regression model consists of a system of several sets of loosely predefined partial differential equations (e.g. logarithmic, linear, polynomial, etc.), the scientists, or rather their computers (in this particular study, the SPSS software package was used for statistical analyses) solve using the experimentally established data. Although statistical analyses like this allow for literally unlimited adjustments for confounding variables, such as body weight, total energy intake, etc., the underlying models are still in and out of themselves theoretical constructs that are based on certain hypothesis and assumptions. Thus, any "associations" of parameter A and outcome B, which are usually expressed in the form of regression coefficients (larger coefficient = greater explanatory power), are valid only if all the underlying assumptions hold true.
Out of the parameters Niramitmahapany et al. evaluated, the only independent variable with a significant impact on the effect of supplemental vitamin D3 on serum levels was the composition (not the absolute amount!) of the fats in the subjects' diets.

Figure 1: Statistically modeled regression coefficients of total fat intake and MUFA/PUFA ratio; adjusted for baseline BMI, 25OHD levels, total energy intake (data adapted from Niramitmahapany.. 2011)
As the regression coefficients in figure 1 clearly show, neither the absolute amount of fats nor the absolute amount of an individual type of dietary fat (monounsaturated, MUFA; polyunsaturated, PUFA; saturated fatty acids, SFA) are adequate predictors of serum 25OHD levels. The ratio of monounsaturated to polyunsaturated fatty acids (MUFA / PUFA ratio) on the other hand turned out to be a pretty reliable predictor of the amount of active vitamin D in the sera of the study participants. This was all the more the case if possible influences of saturated fatty acids were taken into account in the model, as well.

Now, statistics and "associations" are one thing, mechanisms and "causations" are yet another; and obviously the latter, i.e. cause-and-effect relations and determinisms, are what humans, in general, and natural scientists, in particular, have been striving for even before the early days of natural science in the ancient times. Thus, I assume you will be interested to hear, what the scientists have to say with regard to the underlying mechanisms of the statistical "association" they observed:
The mechanisms by which fatty acid intake may influence vitamin D3 absorption have not been completely delineated. Most of the available evidence comes from early work by Hollander and colleagues (Hollander. 1981). Their gut perfusion studies in the rat revealed that vitaminD3 is absorbed by passive diffusion in the proximal jejunumand the distal
ileum (10). Absorption of physiological doses of vitamin D3 in rats was reduced by 30%in the presence of a 4-fold increase in luminal fat (Hollander. 1978; 1981), and consistent with our findings, the PUFA, linoleic and linolenic acids, were particularly effective in decreasing vitaminD3 absorption (Hollander. 1978). Hollander offered several potential explanations for why these fatty acids impaired vitamin D3 absorption. They may have increased the solubility of vitamin D3 in the micelles and changed the partition coefficient such that the vitamin D3 stayed in the micelle. Alternatively, they may have increased the size of the micelle and thereby reduced its diffusion rate and increased its difficulty in crossing the unstirred water layer lining the intestinal mucosa. 
I suppose, what you just read about how dietary fat impairs the absorption of vitamin D goes against all you have hitherto heard from the same "experts" and "gurus" who have been telling you to take 20g of fish oil and 20.000IU of vitamin D, each day. Well, in their defense, it should be said that small amounts of dietary fat are actually beneficial, probably even essential for the uptake of the so-called "fat-soluble" vitamins A, D, K (and probably even E), BUT its obviously not the fat that "drives" or "carries" the vitamins into your blood stream, but the bile acid that is secreted in order to digest the former, which helps with / is necessary for the absorption of these, in the true sense of the word, vital nutrients. Moreover, as Niramitmahapanya et al. state, even evidence for the general accepted claim that vitamin D from small amounts of fish oil "produced a greater increment in 25OHD than vitaminD3 as a powder or dissolved in ethanol" is "inconclusive", ...
because the starting 25OHD levels, study durations, and dosing schedules in the available studies weren’t matched and because increment in 25OHD rather than absorption of parent vitamin D3 was measured.
And studies by Holvik (2007) and Maalouf (2008) which compared identical doses of vitamin D as a powder or in ethanol vs. vitamin D in oil found no difference.
The authors of the study at hand obviously did not look close enough at the data of the Maalouf study, because they state that Maalouf had "found the serum 25OHD increment to be greater with the oil vehicle", which may be correct, but the difference was small and mainly the result of a single 'hyperresponder' within the small study population (N=9 in the respective group). The "greater increment" in the oil group of the Maalouf study is thus statistically irrelevant.
So, while it appears quite clear that the general effect of large amounts of fat taken with physiological doses of vitamin D is a negative one, the scientists cannot explain why mono-unsaturated fatty acids seem to be an exception to the way the other fats (and PUFAs in particular) appear to negatively affect micelle content or migration rate of fat-soluble vitamins in the intestines. Yet, whatever the mechanism may be, an increase or, after all, a reduced decrease in vitamin D3 absorption from the gut may yet be another of the hitherto established health benefits of the long-overlooked mono-unsaturated fatty acids.

Dr. Andro's comment: If you want my personal assessment of these results, take them with an appropriate amount of skepticism. After all, eating meat, fish, liver, eggs, dairy etc., all rich sources of dietary fat and fat soluble vitamins, is the way nature intended us to get part (remember we would synthesize most of our vitamin D from sun exposure) of our vitamin D. So, the only way it would make sense that fat reduces its absorption would be the close association of cholesterol, which is the building block our body uses to manufacture vitamin D, and fatty foodstuff. It would thus be more prudent to say that "fat starvation", which would naturally be associated with low cholesterol intake, is a signal for you body to increase vitamin D uptake, in order to save the valuable cholesterol for the production of other hormones. Instead of avoiding fatty foods, you should thus rather get your lazy ass off the couch and into the sun to put the cholesterol from your 10-egg-breakfast-omelet to good use ;-)