all things vitamin D

[jimmylegs]

Vitamin D, Essential Minerals, and Toxic Elements: Exploring Interactions between Nutrients and Toxicants in Clinical Medicine
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4539504/
"In clinical medicine, increasing attention is being directed towards the important areas of nutritional biochemistry and toxicant bioaccumulation as they relate to human health and chronic disease. Optimal nutritional status, including healthy levels of vitamin D and essential minerals, is requisite for proper physiological function; conversely, accrual of toxic elements has the potential to impair normal physiology. It is evident that vitamin D intake can facilitate the absorption and assimilation of essential inorganic elements (such as calcium, magnesium, copper, zinc, iron, and selenium) but also the uptake of toxic elements (such as lead, arsenic, aluminum, cobalt, and strontium). Furthermore, sufficiency of essential minerals appears to resist the uptake of toxic metals. This paper explores the literature to determine a suitable clinical approach with regard to vitamin D and essential mineral intake to achieve optimal biological function and to avoid harm in order to prevent and overcome illness. It appears preferable to secure essential mineral status in conjunction with adequate vitamin D, as intake of vitamin D in the absence of mineral sufficiency may result in facilitation of toxic element absorption with potential adverse clinical outcomes."

[jimmylegs]

k so have been enjoying some fun times with vertigo the last week or so. decided to check in on the literature to see whether any nutritional links would make sense. science suggested d3 and this study https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4196321/ found serum levels in the 50-60 nmol/L ballpark (ie 23 ng/ml) associated with benign paroxysmal positional vertigo (which is what i have going on).
i had started taking fish oil for the vit d3 in the last little while because i have been inside SO MUCH more than normal this year. but looks like it's time to take things more firmly in hand. will still be stuck inside thesis-ing, but luckily have my handy dandy hi-test 1,000,000 IU/gm d3 drops in the house. should be able to make short work of this issue hopefully. in light of the above, will make certain my multivit/multimineral PLUS mag PLUS zinc also go in. no inadvertent toxin uptake thanks very much hopefully in a few days will be able to report improvements in the vertigo department. if not, will have to dig deeper. fingers crossed however, since d3 came up first in the lit review, and my levels are so likely to be terrible right now. occam's razor and all that. we shall see!

[ElliotB]

Have you tried the Epley Maneuver?

[jimmylegs]

nope, treating it as a nutritional red flag first. if d3 doesn't work i'll give it a go

i just asked google to summarize in non-academic fashion, any epley/d3/vertigo debate via a quick search on terms:
epley maneuver or vit d3 for vertigo

result: http://bit.ly/2eXftNk

[jimmylegs]

didn't end up high dosing today. just 800 iu vit D3 in cod liver oil, plus whatever's in my multi, plus a bunch of other minerals including 360mg elemental magnesium. seems to be an improvement vertigo-wise so far, but will still high dose tomorrow morning (before i head out for some relatively physical volunteer work which would not mix so well with vertigo)

[jimmylegs]

love that people are just stating it right up front finally

not an ms study obvi, but the mag d3 link is relevant

Serum Magnesium and Vitamin D Levels as Indicators of Asthma Severity
https://www.hindawi.com/journals/pm/2016/1643717/abs/
full text d/l link http://downloads.hindawi.com/journals/p ... 643717.pdf
"Background. Serum magnesium levels affect the concentration of circulating vitamin D in blood and subsequently it affects the immunity; thus it plays significant role in the pathogenesis of asthma. Asthma, in adults, is less studied and hypomagnesemia along with vitamin D deficiency and insufficiency is common in asthmatic individuals, which causes frequent asthma attacks, respiratory infections, severe exacerbations, and poor response to bronchodilators. Objective. To detect the magnitude of vitamin D insufficiency and deficiency and serum magnesium levels among asthmatic patients and to correlate them with the severity of asthma. Materials and Methods. This is a cross-sectional case-control study which includes 60 patients of chronic stable asthma and 60 healthy controls. After taking clinical history and systemic examination, pulmonary function test was done. Serum levels of magnesium, 25-hydroxycholecalciferol [25(OH)D], and calcium were measured in all the subjects. Results. Significant correlation was found between vitamin D deficiency, hypomagnesemia, and asthma severity. Serum calcium levels were unaffected by that. Conclusion. Vitamin D and serum magnesium deficiency are highly prevalent in patients with asthma. Increased asthma severity, frequency of attacks, and exacerbation are associated with lower levels of one or both. Serum 25(OH)D and magnesium levels may serve as important markers of asthma severity."

[jimmylegs]

thought this looked like an interesting title:

Controlled trials of vitamin D, causality and type 2 statistical error
http://bit.ly/2irikjZ
"Two recent studies published in The Lancet (Autier et al. (2013) Lancet Diabetes Endocrinol2, 76–89 and Bolland et al. (2014) Lancet Diabetes Endocrinol2, 307–320) have concluded that low levels of vitamin D are not a cause but a consequence of ill health brought about by reduced exposure to the sun, an association known as ‘reverse causality’. The scientific evidence and reasoning for these conclusions are examined here and found to be faulty. A null result in a clinical trial of vitamin D in adults need not lead to a conclusion of reverse causation when low vitamin D is found in observational studies of the same disease earlier in life. To assume an explanation of reverse causality has close similarities with type 2 statistical error..."

they're basically saying, these things aren't all necessarily going to be reversible (A null result in a clinical trial of vitamin D in adults need not lead to a conclusion of reverse causation), so don't go around saying they aren't causal. this is fairly common sense in my view. i have permanent spinal cord damage from b12 deficiency, i just have to deal. and more hyperbolically, if you die from scurvy, no amount of vit c is going to sort that out.

had to go have a closer look at at least one of the guilty authors' works

Vitamin D status and ill health: a systematic review
http://www.sciencedirect.com/science/ar ... 8713701657
"Results from intervention studies did not show an effect of vitamin D supplementation on disease occurrence, including colorectal cancer. In 34 intervention studies including 2805 individuals with mean 25(OH)D concentration lower than 50 nmol/L at baseline supplementation with 50 μg per day or more did not show better results. Supplementation in elderly people (mainly women) with 20 μg vitamin D per day seemed to slightly reduce all-cause mortality. The discrepancy between observational and intervention studies suggests that low 25(OH)D is a marker of ill health. Inflammatory processes involved in disease occurrence and clinical course would reduce 25(OH)D, which would explain why low vitamin D status is reported in a wide range of disorders. In elderly people, restoration of vitamin D deficits due to ageing and lifestyle changes induced by ill health could explain why low-dose supplementation leads to slight gains in survival."

although i'm not at all on board with the idea that inflammatory processes are the cause of low d3, i actually quite agree that low d3 status can be at least in part a marker of ill health. particularly where the illnesses in question have any links to established vit d3 cofactors. i enjoy these related items from discussion in 2014:

http://www.thisisms.com/forum/chronic-c ... ml#p223624

"Magnesium, vitamin D status and mortality: results from US National Health and Nutrition Examination Survey (NHANES) 2001 to 2006 and NHANES III
http://www.biomedcentral.com/1741-7015/11/187/abstract
"High intake of total, dietary or supplemental magnesium was independently associated with significantly reduced risks of vitamin D deficiency and insufficiency respectively. Intake of magnesium significantly interacted with intake of vitamin D in relation to risk of both vitamin D deficiency and insufficiency. Additionally, the inverse association between total magnesium intake and vitamin D insufficiency primarily appeared among populations at high risk of vitamin D insufficiency. Furthermore, the associations of serum 25(OH)D with mortality, particularly due to cardiovascular disease (CVD) and colorectal cancer, were modified by magnesium intake, and the inverse associations were primarily present among those with magnesium intake above the median."

Interactions between magnesium and vitamin D: possible implications in the immune system.
http://www.ncbi.nlm.nih.gov/pubmed/9140864
"Evidence clearly shows that magnesium and vitamin D [1 alpha, 25-dihydroxyvitamin D3; 1,25(OH)2D3] independently affect numerous aspects of the immune system. ... this paper identifies numerous places in common where both magnesium and vitamin D reportedly affect immune function. ... there are compelling reasons to believe that examining interactions between magnesium and vitamin D within the immune system could prove rewarding, especially since the physiological statuses of both nutrients in human populations are less than optimum."

[jimmylegs]

surprised this has not been posted here already - for the record

Essential Nutrient Interactions: Does Low or Suboptimal Magnesium Status Interact with Vitamin D and/or Calcium Status?
http://advances.nutrition.org/content/7/1/25.short
Although much is known about magnesium, its interactions with calcium and vitamin D are less well studied. Magnesium intake is low in populations who consume modern processed-food diets. Low magnesium intake is associated with chronic diseases of global concern [e.g., cardiovascular disease (CVD), type 2 diabetes, metabolic syndrome, and skeletal disorders], as is low vitamin D status. No simple, reliable biomarker for whole-body magnesium status is currently available, which makes clinical assessment and interpretation of human magnesium research difficult. Between 1977 and 2012, US calcium intakes increased at a rate 2–2.5 times that of magnesium intakes, resulting in a dietary calcium to magnesium intake ratio of >3.0. Calcium to magnesium ratios <1.7 and >2.8 can be detrimental, and optimal ratios may be ∼2.0. Background calcium to magnesium ratios can affect studies of either mineral alone. For example, US studies (background Ca:Mg >3.0) showed benefits of high dietary or supplemental magnesium for CVD, whereas similar Chinese studies (background Ca:Mg <1.7) showed increased risks of CVD. Oral vitamin D is widely recommended in US age-sex groups with low dietary magnesium. Magnesium is a cofactor for vitamin D biosynthesis, transport, and activation; and vitamin D and magnesium studies both showed associations with several of the same chronic diseases. Research on possible magnesium and vitamin D interactions in these human diseases is currently rare. Increasing calcium to magnesium intake ratios, coupled with calcium and vitamin D supplementation coincident with suboptimal magnesium intakes, may have unknown health implications. Interactions of low magnesium status with calcium and vitamin D, especially during supplementation, require further study.

[jimmylegs]

Safety and immunologic effects of high-vs low-dose cholecalciferol in multiple sclerosis
http://www.neurology.org/content/early/ ... hort?rss=1
full text: http://bit.ly/2mbrHcV

considering it took years for high dose d3 to cause a problem for me, and with that particular issue having been with magnesium, i'll continue to look forward to longer term studies which examine d3's effects on essential nutrients other than calcium.

[jimmylegs]

scant handful of case studies demonstrating no adverse effects within the scope of their assessment. looking forward to similar but larger studies where magnesium status is part of the evaluation.

McCullough, P., & Amend, J. (2016). Results of Daily oral Dosing with up to 60,000 International Units (iu) of vitamin d3 for 2 to 6 years in 3 adult males. The Journal of Steroid Biochemistry and Molecular Biology.
http://www.sciencedirect.com/science/ar ... 6016303569

[jimmylegs]

went hunting for older info, for context re the kinds of oral vit d doses that have resulted in hypercalcemia.

found this one (still in the land of case studies)

An Unusual Case of Hypercalcemia
https://www.ncbi.nlm.nih.gov/pmc/articl ... 5-0026.pdf
"... complained of facial paresthesiae and the next day Chvostek's and Trousseau's signs became positive. The serum calcium was 7.3 mg/100 ml. Treatment was given, in the form of calcium gluconate and calciferol by mouth, with gradual disappearance of symptoms,
and return of the serum calcium to normal.
By the time of discharge, she was stabilized on calciferol 1.25 mg twice daily (100 000 units daily) and dihydrotachysterol 1 ml daily. She was also placed on L-thyroxine 0.1 mg twice daily. For the next fifteen years {JL: !!) she remained well, apart from the occurrence of a carcinoma of the sigmoid colon, which was successfully resected in 1965 (Histology: poorly differentiated, Dukes' stage B). She remained normocalcemic throughout this period...

"In January 1973, at the age of 65, she attended for routine follow up, and again complained of paresthesiae, this time in the hands. The serum calcium a month before had been in the normal range (9.9 mg/100 ml) and it was thought she might now be frankly hypocalcaemic. Blood was taken for serum calcium, and meanwhile her calciferol was increased from 2 tablets daily (100 000 units) to 3 tablets daily (150 000 units). At her next visit, five weeks later, it was found that her serum calcium had been 11.7 mg/100 ml,
somewhat surprising in view of her symptoms. The calciferol was therefore reduced to its former dosage of 100 000 units daily.

"Three months later (in June 1973), she complained of nausea, giddiness, headaches, constipation and polyuria. She looked unwell, but no specific abnormality was found on examination. She was admitted forthwith for investigation. Investigations: Serum calcium 14.1 mg/100 ml. ... Serum cholecalciferol levels 161, 175, 176 ng/ml (normal range 7-40 ng/ml).
(JL: converting patient levels here gives 400-440 nmol/L and 'normal' range 17-100 nmol/L)

"Calciferol was stopped on admission, and the serum calcium slowly fell, over about a month, to 12.5 mg/100 ml. At that point for reasons unexplained (? bed rest), it started to rise again, and reached 14.6 mg/100 ml, higher than whilst taking calciferol.

"A three-week course of prednisolone, starting with 60 mg daily and reducing to zero, resulted in a fall of serum calcium from 14.6 to 9.3 mg/100 ml, with a correspondingly dramatic improvement in the patient's clinical state. By the end of another fortnight, her serum calcium had again risen to 13.2 mg/100 ml. A further course of prednisolone was then given, this time for a week only; the serum calcium again fell, to 11.0 mg/100 ml. Thereafter, on neither calciferol nor prednisolone, there has been a slow downward trend of the serum calcium toward normal (Fig 2). Our most recent value, on 1.3.74, is 9.9 mg/100 ml.
All this time, the patient's clinical state paralleled the serum calcium level. Above 11 mg/100 ml, she experienced nausea, malaise and polyuria; when normocalcemic, she felt perfectly well.

"The main point of interest is the continuing hypercalcmemia after discontinuation of calciferol. Several differential diagnostic possibilities emerge.
(1) That the biological half-life of exogenous calciferol (vitamin Ds) is exceedingly long - perhaps a year or more (Dent 1966). In this case the additional tablet of calciferol was given for a period of only five weeks.
...
"The confirmatory evidence came in the form of three grossly elevated serum cholecalciferol levels, taken at least two months after stopping calciferol. These levels indicated that the drug was still present in the body, and that the correct interpretation of this problem was the first mentioned above - namely, that exogenous calciferol possesses an exceedingly long half-life in vivo."

we can likely assume the 'calciferol' in question was d2, since you couldn't even get 50K d3 in pill form as late as 2006 (and i have no idea if it's even available now - i still use 1,000,000 IU/gm d3 liquid, dosed out in a syringe).
https://dailymed.nlm.nih.gov/dailymed/a ... veid=26181

given the markedly lower efficacy of oral d2 in terms of affecting serum d3 levels, it makes sense that this patient was able to tolerate the high dose, of D2 in particular, for so many years.

Armas, L. A., Hollis, B. W., & Heaney, R. P. (2004). Vitamin D2 is much less effective than vitamin D3 in humans. The Journal of Clinical Endocrinology & Metabolism, 89(11), 5387-5391.
https://www.ncbi.nlm.nih.gov/pubmed/15531486

"Vitamin D2 potency is less than one third that of vitamin D3. Physicians resorting to use of vitamin D2 should be aware of its markedly lower potency and shorter duration of action relative to vitamin D3."

Tripkovic, L., Lambert, H., Hart, K., Smith, C. P., Bucca, G., Penson, S., ... & Lanham-New, S. (2012). Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis. The American journal of clinical nutrition, 95(6), 1357-1364.
http://ajcn.nutrition.org/content/95/6/1357.full.pdf

"This meta-analysis indicates that vitamin D3 is more efficacious at raising serum 25(OH)D concentrations than is vitamin D2, and thus vitamin D3 could potentially become the preferred choice for supplementation..."

still more digging to do, but that was an interesting little read.

[jimmylegs]

going forward in time from the above, this is basically the next study i find with the search terms i'm using, (namely "serum calcium" "serum cholecalciferol" hypercalcemia)

Heaney, R. P., Davies, K. M., Chen, T. C., Holick, M. F., & Barger-Lux, M. J. (2003). Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. The American journal of clinical nutrition, 77(1), 204-210.
http://ajcn.nutrition.org/content/77/1/204.full.pdf

familiar territory - this was the study i used in 2006 to justify my proposed 4000 IU/d regimen with my GP.

it would be interesting to see this study repeated but with a baseline magnesium status taken, plus assessments for effects of different combinations of magnesium intake (properly timed, and not a crappy insoluble form) in parallel with the d3.

next one again (another 'old friend' among studies):

Holick, M. F. (2005). The vitamin D epidemic and its health consequences. The Journal of nutrition, 135(11), 2739S-2748S.
http://jn.nutrition.org/content/135/11/2739S.long
"Vitamin D intoxication that includes hypercalcemia, typically, is not observed until the 25(OH)D reach levels of at least 375 nmol/L (150 ng/mL) (45)."

this assertion directs us to another single case study (which actually contains zero hits on '150' and 375'):

"45. Koutkia P, Chen TC, Holick MF. Vitamin D intoxication associated with an over-the-counter supplement. N Engl J Med. 2001;345:66-67."
http://www.nejm.org/doi/pdf/10.1056/NEJM200107053450115

"We describe a patient with hypercalcemia associated with the ingestion of an over-the-counter vitamin D supplement. A 42-year-old man was hospitalized with symptoms of hypercalcemia of a few weeks’ duration. For the past two years, he had been taking a supplement that contained vitamin D3. On admission his serum levels were as follows: 25-hydroxyvitamin D, 487.3 ng per milliliter (normal range, 8.9 to 46.7); calcium, 15.0 mg per deciliter (normal range, 8.8 to 10.1); creatinine, 2.4 mg per deciliter; and hemoglobin, 10.5 mg per deciliter (all measurements were performed at the Nichols Institute, San Juan Capistrano, Calif.). ...

"The patient sent us two bottles of his vitamin D3 supplement (Prolongevity, Markham, Ont., Canada), and we purchased one from the manufacturer. All supplements were from different lots. The vitamin D3 supplement was extracted with methanol and analyzed by high-performance liquid chromatography.4 The supplements from each of the three lots that we analyzed contained a mean of 1.3±0.1 mg, 12.8±0.1 mg, and 21.7±0.2 mg of vitamin D3 per gram of powder, respectively, or about 26 to 430 times the amount
listed by the manufacturer (2000 IU or 50 µg of vitamin D per gram of powder). The patient consumed one teaspoon (or 3 g) of powder daily, or 156,000 to 2,604,000 IU of vitamin D3 per day. This amount was 78 to 1302 times the recommended safe upper limit of 2000 IU per day."

so this guy was WAY overdoing D3 for just 2 yrs, compared to milady with the D2 for 15 yrs and more.
the only place i can pull the figure 150 from this letter to the editor, is in figure 1 where in this single patient, at 10 months in, serum calcium levels are recorded within normal limits once d3 drops below 150. 'typically'?? that's an interesting stretch. 10 years ago, i would not have imagined that the evidence for a statement like "Vitamin D intoxication that includes hypercalcemia, typically, is not observed until the 25(OH)D reach levels of at least 375 nmol/L (150 ng/mL)" would be so thin.

[jimmylegs]

would be interesting if they had looked at magnesium for this study as well. might have gone some way to explain those recalcitrant subjects whose levels did not exceed 32 ng/ml?

Ilahi, M., Armas, L. A., & Heaney, R. P. (2008). Pharmacokinetics of a single, large dose of cholecalciferol. The American journal of clinical nutrition, 87(3), 688-691.
http://ajcn.nutrition.org/content/87/3/688.full.pdf

"We saw that in several of our subjects even this large dose did not raise their calcidiol concentrations >32 ng/mL. Distinguishing features of these subjects were their low baseline calcidiol concentrations (between 15 and 18 ng/mL) and 1 subject was African American ... From this study we can safely recommend 100 000 IU cholecalciferol dosed every 2 mo in persons with moderate baseline calcidiol concentrations. However, in those persons with baseline calcidiol concentrations <20 ng/mL, even this large dose will not adequately raise their calcidiol concentrations."

still wish i knew whether there is a measurable effect of my careful attention to mag status. i like the studies that exist to show variable response to d3 intake from sun and oral sources depending on background mag status. but testing mag and d3 *treatment* together would be great.

[jimmylegs]

this is the next study that comes up with the search terms i'm using:

Mailhot, G. (2012). Vitamin D bioavailability in cystic fibrosis: a cause for concern?. Nutrition reviews, 70(5), 280-293.
https://academic.oup.com/nutritionrevie ... fibrosis-a
"Despite the inclusion of extra vitamin D in their regimen of fat-soluble vitamin supplementation, cystic fibrosis patients remain chronically depleted of vitamin D. The persistence of suboptimal vitamin D status is often blamed on the maldigestion and malabsorption of fat. However, the mitigated success of recent clinical trials with high-dose vitamin D supplementation suggests that vitamin D bioavailability might be impaired in these patients."

hmmm what *could* be going on there.

Magnesium in cystic fibrosis—Systematic review of the literature (2016)
http://onlinelibrary.wiley.com/doi/10.1 ... 23356/full
"The first comprehensive review of the literature confirms that, despite being one of the most prevalent minerals in the body, the importance of magnesium in cystic fibrosis is largely overlooked. In these patients, hypomagnesemia should be sought once a year. Furthermore, the potential of supplementation with this cation deserves more attention."

i think we can assume the authors do not mean hypomagnesemia should be inflicted on patients annually...

[jimmylegs]

back on track with hypercalcemia. not playing in the same ballpark at all with dialysis, but interesting anyway

Zitt, E., Sprenger-Mähr, H., Mündle, M., & Lhotta, K. (2015). Efficacy and safety of body weight-adapted oral cholecalciferol substitution in dialysis patients with vitamin D deficiency. BMC nephrology, 16(1), 128.
http://citeseerx.ist.psu.edu/viewdoc/do ... 1&type=pdf
"Patients received a mean weekly cholecalciferol dose of 7603 ±1855 IU. After six months of substitution 25OHD3 increased to 26.1 ± 8.8 ng/mL (P < 0.01) with a mean increase of 16.2 ± 7.8 ng/mL. At the end of the study 14 (27 %) patients had a 25OHD3 level >30 ng/mL, and all 37 (73 %) other patients a level >20 ng/mL. Serum calcium and phosphorous remained constant. Figure 2 shows the course of monthly serum calcium and phosphorous levels during the whole study period. We observed six hypercalcemic episodes (serum calcium >2.55 mmol/L) representing 1.9 % of all monthly measurements (n = 306). Hypercalcemia was noted in four patients (three patients with one
episode, one patients with three episodes)."

would be interesting if we could see better detail of the individuals who experienced hypercalcemia on one or more occasions.

different kind of mag connection in this kind of study. recall this poor fellow however (orig pdf link no longer works but you can still easily get a snippet of the article via pdiconnect, and i had also posted excerpts as follows)

Gabapentin for intractable hiccups in a patient undergoing peritoneal dialysis
http://www.pdiconnect.com/content/28/6/667.extract
"Hiccups are involuntary, rhythmic, spasmodic contractions of the diaphragm. ... hiccups became frequent and severe enough to produce insomnia, anorexia, and weight loss. His other medical problems included hypertension, ischemic heart disease, gout and anemia secondary to ESRF. ... Laboratory investigations were as follows: .... magnesium 0.66 mmol/L ... gabapentin was further increased to 600 mg nightly, leading to the hiccups disappearing over a 3 month follow up period"

frustrating that the docs would allow apparently symptomatic mag deficit to persist, and try to treat the symptoms with a pharma product, without even giving essential mag a chance at the issue, apparently for fear of mag excess in dialysis.

related:
Magnesium in chronic kidney disease Stages 3 and 4 and in dialysis (2012)
https://academic.oup.com/ckj/article/5/ ... es-3-and-4
"However, in more advanced CKD (as creatinine clearance falls <30 mL/min), this compensatory mechanism becomes inadequate such that overt hypermagnesaemia develops frequently in patients with creatinine clearances <10 mL/min."

Magnesium in dialysis patients: serum levels and clinical implications (1998)
https://www.ncbi.nlm.nih.gov/pubmed/9696434
"Hypermagnesemia in these patients is frequent, usually mild (serum magnesium lower than 1.5 mmol/l) and asymptomatic, but severe and symptomatic hypermagnesemia can be induced by exogenous magnesium administration." (recall se mg level was 0.66 mmol/l for gentleman with the chronic hiccups)

they're working their way around to it more recently, looks like:

Magnesium and outcomes in patients with chronic kidney disease: focus on vascular calcification, atherosclerosis and survival (2012)
https://academic.oup.com/ckj/article/5/ ... th-chronic
"Patients with chronic kidney disease (CKD) have a high prevalence of vascular calcification, and cardiovascular disease is the leading cause of death in this population. ... Magnesium is a natural calcium antagonist and both human and animal studies have shown that low circulating magnesium levels are associated with vascular calcification. Clinical evidence from observational studies of dialysis patients has shown that low-magnesium levels occur concurrently with mitral annular calcification, peripheral arterial calcification and increased carotid intima–media thickness. Few interventional studies have been performed. Two interventional studies suggest that there may be benefits such as retardation of arterial calcification and/or reductions in carotid intima–media thickness in response to magnesium supplementation in CKD patients, though both studies have limitations. ... observational studies have shown that low serum magnesium may be an independent risk factor for premature death in CKD patients, and patients with mildly elevated serum magnesium levels could have a survival advantage over those with lower magnesium levels."

imagine that - add mag to help combat vascular calcification *and* low vit d3.