4/26/2020 Magnesium Could be in Charge of Your Vitamin D Levels: Supplements Lower High and Increases Low 25OHD Levels

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Magnesium Could be in Charge of Your Vitamin D Levels:
Supplements Lower High and Increases Low 25OHD Levels Quick Take: Only 25% Puta-
tively Anabolic Laxogenin
If you subscribed to the @SuppVersity Supps Contain Measurable
Facebook Page, you will have read the Amounts of the Alleged Mus-
news, already: "Magnesium status and cle Builder
supplementation influence vitamin D
Freezing, Defrosting, Toast-
status and metabolism" (Dai 2018) - that ing, and Your Glucose Re-
is both the title and the main results of a sponse to White Bread | Addi-
recent study from the Vanderbilt tives Ruin Part of the 30-37%
University that is important enough to Benefit
make it from the short format on
Facebook to a detailed SuppVersity Does Eating Beans W/B4
Meals Have the Same Blood
article of its own - the article at hand ;-) D3 and Mg Supplements not mandatory w/ sun + balanced diet Sugar Lowering, and Fat Loss
Promoting as 'Carb-
The 25OHD-balancing effects Dai et al. observed in their 180 participants (aged 40–85 y) could after all Blockers'?
do much more than point towards a reason why everyone and his mama seems to be D-ficient - it could
SuppVersity - Nutrition and Exercise Science for Everyone
force us to redefine what "optimal" 25OHD levels are - significantly below those many Internet "health
experts" recommend. Alternate Day Fasting & Classic
Dieting: Same >5% Weight Loss in 57 vs.
67 Days W/ Unwittingly Increased Deficits
Learn more about vitamin D at the SuppVersity
'Spiking' (not Replacing) Suboptimal
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4/26/2020 Magnesium Could be in Charge of Your Vitamin D Levels: Supplements Lower High and Increases Low 25OHD Levels - SuppVersity: Nutrition and Exercise Science for Everyone
Vitamin D Shall Vitamin D and Up Exercise or Eggs Satisfy Essential Supp Suggestions for Blood Flow Restriction Training 2020:
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The study is a National Cancer Institute independently funded ancillary study, nested within the The Latest on Artificial Sweeteners:
"Personalized Prevention of Colorectal Cancer Trial" (PPCCT), which enrolled 250 participants at risk of #Sucralose Good for the Lean, Bad for the
developing colorectal cancer. The PPCCT is a double-blind 2 × 2 factorial randomized controlled trial Obese? #Acesulfame-K, the Healthier
conducted in the Vanderbilt University Medical Center. Alternative? As If! Plus: There's All Wrong
w/ the Research

Customized supplementation with magnesium glycinate brought the subjects' total magnesium #Coffee & Related Research from
into the range of the RDA (men 400-420 mg/d, women 310-320 mg/d) Early 2020: #FilterHeight Matters | #Leaves
Better Than Beans | #Probiotic Coffee
What makes the study stick out is that doses for both magnesium and placebo were customized based
on baseline dietary intakes - in other words: The less magnesium in the diet, the more was
supplemented. Furthermore, the scientists tested not just 25OHD (which is what your doctor will test if Most Popular (last 30 days)
you ask for a "vitamin D test") but also changes in plasma 25-hydroxyvitamin D3 [25(OH)D3], 25-
hydroxyvitamin D2 [25(OH)D2], 1,25-dihydroxyvitamin D3, 1,25-dihydroxyvitamin D2, and 24,25- SuppVersity EMG Series -
Rectus Abdominis, Obliques
dihydroxyvitamin D3 [24,25(OH)2D3] - all by liquid chromatography–mass spectrometry.
and Erector Spinae: The Very
Best Exercises For Sixpack
Based on the somewhat disappointing observation that vitamin D was not related to cardiovascular Abs and a Powerful
disease in the recent VITAL trial (Kubiak 2018) - even in subjects with baseline vitamin D insufficiency(!) Midsection
- the researchers whose current main objective is to elucidate the role that magnesium may play with
cancer as part of the previously mentioned "Personalized Prevention of Colorectal Cancer Trial" SuppVersity EMG Series -
Gluteus maximus,
speculated that "magnesium supplementation differentially affects vitamin D metabolism dependent on
Quadriceps femoris,
baseline 25-hydroxyvitamin D [25(OH)D] concentration" (Dai 2018). Gastrocnemius, Soleus &
More: The Very Best
In previous experiments, the scientists had already observed that people's ability to synthesize Exercises for Tree-Trunk
"vitamin D" depended on their magnesium status. Legs and Herculean Calves

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About both, the US's vitamin D and magnesium status, co-author Martha Shrubsole, Ph.D., research Latissimus, Trapezius &
professor of Medicine, points out in the corresponding press release: More: The Very Best
Exercises for Back Width &
"Vitamin D insufficiency is something that has been Thickness
recognized as a potential health problem on a fairly
large scale in the U.S. A lot of people have received
recommendations from their health care providers
to take vitamin D supplements to increase their Find Things on the SuppVersity
levels based upon their blood tests.
Search
In addition to vitamin D, however, magnesium
deficiency is an under-recognized issue. Up to 80
percent of people do not consume enough
magnesium in a day to meet the recommended
Physical Culture for Your Ears
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4/26/2020 Magnesium Could be in Charge of Your Vitamin D Levels: Supplements Lower High and Increases Low 25OHD Levels - SuppVersity: Nutrition and Exercise Science for Everyone
dietary allowance (RDA) based on those national
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[Worth mentioning:] "Shrubsole stressed that the Young Blood Revives Muscle, Brain &
magnesium levels in the trial were in line with RDA More | Plus: 6+ Less 'Horrific'
guidelines, and she recommended dietary changes Alternatives
as the best method for increasing intake. Foods
with high levels of magnesium include dark leafy Super Human Radio
greens, beans, whole grains, dark chocolate, fatty SHR # 2048 :: Grasslands Beef + Why
fish such as salmon, nuts and avocados." (ibid.). Patreon + Sun Protection from the
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Incidentally, the hypothesis that these two deficiency
nutrients may interact is not even new. You can go back
as far as 50 years and will find (rodent) studies showing
how vitamin D affects not just calcium but also
magnesium levels (Harrison 1964). Hitherto, though, Magnesium is at the center of vitamin D
this interaction has often been ascribed to the ability of metabolism - as part of CYP, cytochrome
P450 enzymes (dark gray indicates
vitamin D to increase Mg absorption irrespective of deactivating enzymes, and light gray
one's vitamin D status. indicates activating enzymes | Dai 2018)

Having high(er) 25OHD levels was found to be associated with 11-13% reduced all-cause mortality hazards in a 2013 study
using data from NHANES 2001-06 - for those of the subjects that consumed high(er) amounts of magnesium the hazard
reduction compared to D-ficient levels of <20ng/ml was 23%-30% and the overall HRs up to 20% lower (Deng 2013).

The opposite, i.e. putative effect of magnesium on vitamin D, on the other hand, has been largely
ignored - despite the fact that more recent studies, such as Deng et al. 2013, in which the authors
analyzed NHANES data from 2001 to 2006 seem to suggest that there's a two-way interaction of

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4/26/2020 Magnesium Could be in Charge of Your Vitamin D Levels: Supplements Lower High and Increases Low 25OHD Levels - SuppVersity: Nutrition and Exercise Science for Everyone
magnesium and vitamin D in relation to risk of both vitamin D deficiency and insufficiency - with literally
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Which Mg is best? Plasma an bone (primary axis) as well as red blood cell (RBC; 2ndary axis(!)) content after 14 days of
supplementation with identical amounts of magnesium in different organic and inorganic forms (Coudray. 2005 | learn more)
- unfortunately, the study was conducted in rodents and used only gluconate, not glycinate as it was used in the PPCT trial.

Now, we shouldn't forget that, in Deng's study, we're talking about correlations/associations of which
Zittermann in a 2013 writes that it "provides important findings concerning potential metabolic
interactions between magnesium and vitamin D and its clinical relevance.

I've heard the vitamin D test is inaccurate - Is that

accurate or #fakeNews? Accurate. As Holick points
out in a 2009 paper, "the first assays for 25(OH)D
used the competitive protein binding format with the
vitamin D binding protein (DBP) as the binder" -
advantage: recognizes 25(OH)D2 equally as well as
25(OH)D3; disadvantage: the assay will also
measure all sorts of D-metabolites including 24,25-
dihydroxyvitamin D [24,25(OH)2D], 25,26-
dihydroxyvitamin D and the 25,26-dihydroxyvitamin
D -26, 23-lactone, which reduces the accuracy by
~10-15%.

The same issue(s) exist(s) for the radioimmunoassay

(RIA | Diasorin@) which "typically overestimated
25(OH)D levels by approximately 10-20%" (ibid).
Moreover, IDS has recently developed an RIA "which
has a 100% specificity for 25(OH)D3 and only 75%
specificity for 25(OH)D2 (ibid) and could thus be a
more accurate alternative (still, if you're D-ficient or
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4/26/2020 Magnesium Could be in Charge of Your Vitamin D Levels: Supplements Lower High and Increases Low 25OHD Levels - SuppVersity: Nutrition and Exercise Science for Everyone
not often depends on which lab you're using (see
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So how do you get the absolute accurate levels? You

don't... well, actually you don't have to. Scientists, on
the other hand, should use liquid chromatography
tandem mass spectroscopy (LC-MS) to measure
25(OH)D in human serum, directly. This assay
quantitatively measures both 25(OH)D2 and
25(OH)D3.

However, results should be considered preliminary

since biochemical data on individual magnesium status
were lacking, [and] confounding cannot be excluded"
(Zittermann 2013). That's in contrast to the more
recent observations by Dai et al. whose data come
from a tightly controlled clinical trial - a trial that clearly
suggests this link could be mechanistic.

The relationship between 25OHD and magnesium

is complex and probably U-shaped

Mechanistic, but not simplistic, to be more precise: In
the latest study by Dai et al. the relations between
magnesium treatment and plasma concentrations of
25(OH)D3, 25(OH)D2, and 24,25(OH)2D3 were
significantly different depending on the baseline
concentrations of 25(OH)D, and significant interactions
persisted after Bonferroni corrections (meaning
including statistical correction of multiple comparisons
which increase the likelihood of false positives). More
specifically, the subjects from the "Personalized Prevention of Colorectal Cancer Trial" whose data the
Vanderbilt scientists analyzed revealed that ...
In 10 lab-workers, the mean serum 25(OH)D
varied widely [from 17.1 (4.6) to 35.6 (5.2)
ng/ml; P < 0.005] between laboratories (error
bars represent SEM). B, Similarly, marked
within-individual variation was observed in
25(OH)D measurement in different
laboratories. This means: Whether an
individual has hypovitaminosis D (threshold =
dashed line) depends on which laboratory was
used.

magnesium supplementation increased the 25(OH)D3

concentration when baseline 25(OH)D concentrations
were close to 30 ng/mL, ...

but decreased the levels of 25(OH)D3 when the

baseline 25(OH)D was higher (from ∼30 to 50 ng/mL |
insufficient data to reliable statements about even
higher concentrations);

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4/26/2020 Magnesium Could be in Charge of Your Vitamin D Levels: Supplements Lower High and Increases Low 25OHD Levels - SuppVersity: Nutrition and Exercise Science for Everyone

moreover, at higher baseline 25OHD concentrations,

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other 25OHD metabolites, i.e. 25-hydroxyvitamin D2
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[25(OH)D2], and 24,25-dihydroxyvitamin D3
[24,25(OH)2D3] were likewise affected by magnesium
supplements, how and at which levels this affects the
hitherto often ignored ratio of these D-metabolites and
hence our health will have to be elucidated in future
studies, though (see figure below).

Overall, the provision of (sufficient =RDA) magnesium

seems, as the authors from Vanderbilt University rightly
point out, to allow our bodies to keep our 25OHD levels
within the middle range of a previously established and
repeatedly confirmed U-shaped curve that illustrates the
general or specific cardiovascular disease risk as a function
of serum 25OHD levels (Ross 2011; Abraham 2011).
The main result of the study: The provision
of adequate (RDA) amounts of magnesium
seems to help balance the 25OHD levels
of the subjects in the PPCCT trial at
~30ng/ml.

Somewhat surprising for the "more is more" proponents, high 25OHD3 and 24,25(OH)2D3 decreased with magnesium
supplementation; the often derided 25(OH)D2, on the other hand, increased (Dai 2018).

In the discussion of the results, Dai et al. (2018) write that "magnesium supplementation may not only
accelerate the metabolism and degradation of 25(OH)D3 but also shift CYP3A4 to selectively degrade
vitamin D3 over vitamin D2 when plasma 25(OH)D is high" - it doesn't take a scientists to realize that
the findings of the study at hand thus "provide the first evidence that adequate magnesium status could
potentially prevent vitamin D–related adverse events" (Dai 2018).

The existence of such a "comfort zone" is also in line with some recently published paper in the Journal
of Steroid Biochemistry and Molecular Biology in which Mohammed S. Razzaque highlights that
"Vitamin D status is more likely to be a consequence rather than a cause of a disease" (Razzaque
2018). That magnesium may help keeping your levels within this "comfort zone" may hence be either
the results of direct interactions or simply the consequence of the well-proven cardiovascular and
metabolic benefits of getting enough of the precious mineral in your diet.

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4/26/2020 Magnesium Could be in Charge of Your Vitamin D Levels: Supplements Lower High and Increases Low 25OHD Levels - SuppVersity: Nutrition and Exercise Science for Everyone

Another
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although Dai et al. rightly point out that, in spite full-blown
deficiency intakes in 79% of US adults (NHANES), sufficient
amounts of magnesium can be easily consumed with our diet
if the latter contains copious amounts of foods with high levels
of magnesium include dark leafy greens, beans, whole grains,
fatty fish such as salmon, nuts, avocados and dark chocolate!

In this context, it seems appropriate to remind you that the

overall result of the study at hand underlines the futility of the
Western concept "more helps more", which doesn't seem to
hold for vitamin D. In fact, it may well fail you when it comes to
magnesium supplementation, too... and I am not just talking More Than a Diet Myth? Dark
about magnesium (and other nutrient) losses due to the Chocolate/Cacao Won't Get You
Jacked, but it May Help Maintain a
laxative effects of the Internet's favorite macromineral, here
Slim Waist Over Time | read the
(noteworthy in this context: 1st study on transdermal whole SuppVersity Classic
magnesium + Mg-bioavailability).

From a mechanistic perspective, the interaction could be a result of the previously illustrated role of
magnesium in vitamin D metabolizing enzymes: 1α-hydroxylase (i.e., CYP27B1) and 24-
hydroxylase (i.e., CYP24A1), which synthesize and metabolize 25(OH)D and 1,25(OH)2D,
respectively. In that, the study at hand is the first large(r)-scale study to (a) be done in people w/out
severe Mg-deficiency and to (2) show that normalizing magnesium will not simply increase 25OHD,
but seems to modulate it towards ~30-40ng/ml. This warrants mentioning that similar interactions
do/could exist with calcium & phosphorus (Harrison 1958; Gray 1977), as well as potassium (Bikle
1978; Rafferty 2008) and salt (Breslau 1982). And guess what: One of them, i.e. calcium or rather a
Ca:Mg ratio of ≥2.6, which has previously been found in >76% of the US general adult population, is
also characteristic of the subjects in the study at hand - whether high Ca:Mg diets actually 'cause
the vitamin D deficiency epidemic will yet have to be elucidated in future studies | Comment!

References:

Abraham, Paul S., et al. "The vitamin "D-bate": what vascular risk in geriatric inpatients?"
Journal of the American Geriatrics Society 59.8 (2011): 1556-1558.

Bikle, Daniel D., and H. Rasmussen. "A biochemical model for the ionic control of 25-
hydroxyvitamin D3 1alpha-hydroxylase." Journal of Biological Chemistry 253.9 (1978):
3042-3048.

Binkley, N., et al. "Assay variation confounds the diagnosis of hypovitaminosis D: a call for
standardization." The Journal of Clinical Endocrinology & Metabolism 89.7 (2004): 3152-
3157.

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4/26/2020 Magnesium Could be in Charge of Your Vitamin D Levels: Supplements Lower High and Increases Low 25OHD Levels - SuppVersity: Nutrition and Exercise Science for Everyone

Breslau, Neil A., et al. "The role of dietary sodium on renal excretion and intestinal
This site uses cookies to help deliver services. By using this site, you agree to the use of cookies.
absorption of calcium and on vitamin D metabolism." The Journal of Clinical Endocrinology
LEARN MORE GOT IT!

& Metabolism 55.2 (1982): 369-373.

Dai, et al. "Magnesium status and supplementation influence vitamin D status and
metabolism: results from a randomized trial." The American Journal of Clinical Nutrition,
108.6(1) (2018).

Deng, Xinqing, et al. "Magnesium, vitamin D status and mortality: results from US National
Health and Nutrition Examination Survey (NHANES) 2001 to 2006 and NHANES III." BMC
medicine 11.1 (2013): 187.

Gray, Richard W., et al. "The importance of phosphate in regulating plasma 1, 25-(OH) 2-
vitamin D levels in humans: studies in healthy subjects, in calcium-stone formers and in
patients with primary hyperparathyroidism." The Journal of Clinical Endocrinology &
Metabolism 45.2 (1977): 299-306.

Harrison, Helen C., Harold E. Harrison, and Edwards A. Park. "Vitamin D and citrate
metabolism: effect of vitamin D in rats fed diets adequate in both calcium and phosphorus."
American Journal of Physiology-Legacy Content 192.2 (1958): 432-436.

Harrison, Harold E., and Helen C. Harrison. "The interaction of vitamin D and parathyroid
hormone on calcium phosphorus and magnesium homeostasis in the rat." Metabolism-
Clinical and Experimental 13.10 (1964): 952-958.

Holick, Michael F. "Vitamin D status: measurement, interpretation, and clinical application."

Annals of epidemiology 19.2 (2009): 73-78.

Kubiak, Julia, et al. "Vitamin D supplementation does not improve CVD risk factors in
vitamin D-insufficient subjects." Endocrine connections 7.6 (2018): 840-849.

Rafferty, Karen, and Robert P. Heaney. "Nutrient effects on the calcium economy:
emphasizing the potassium controversy." The Journal of nutrition 138.1 (2008): 166S-171S.

Ross, A. Catharine, et al. "The 2011 report on dietary reference intakes for calcium and
vitamin D from the Institute of Medicine: what clinicians need to know." The Journal of
Clinical Endocrinology & Metabolism 96.1 (2011): 53-58.

Tuohimaa, Pentti, et al. "Both high and low levels of blood vitamin D are associated with a
higher prostate cancer risk: a longitudinal, nested case‐control study in the Nordic
countries." International Journal of Cancer 108.1 (2004): 104-108.

Zittermann, Armin. "Magnesium deficit-overlooked cause of low vitamin D status?." BMC

medicine 11.1 (2013): 229.

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Labels: 25-(OH) D3, 25(OH)2D, 25(OH)D, 25OHD, health, magnesium, vitamin D, vitamin D3

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