Tag: atherosclerosis

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Links on heart disease, calcium and iodine

Whether nutrient deficiencies or other metabolic imbalance is the cause is not clear or it may be a response to oxidative stress, however levels of the trace nutrients magnesium, selenium, zinc, and vitamin D3 were found to be low and the level of calcium elevated in myocardium, a type of muscle tissue in the heart. (1)

The short story – adequate nutrition is needed to support pregnancy and lactation (breast feeding) – longer duration breast feeding (6-12 months or more) is associated with less heart disease (2) and breast cancer (3) risk. Increased amounts of iodine is needed for pregnancy and lactation (4) and low iodine and low selenium may be involved in breast cancer risk. (5)

A high protein diet, especially one high in dairy products is associated with more heart disease risk. (6) Background information – a high protein diet creates more work for the kidneys in order to excrete the extra nitrogen from protein that was converted into energy (ketones) (7) (29) instead of being used to build muscle or other proteins.

Magnesium may help protect against calcification in heart disease in two important ways. It is needed for the kidneys to be able to excrete excess calcium. It also acts as a calcium channel blocker by providing electrical power from inside of cells or organ tissue in order to help keep excess calcium from entering the soft tissue and blood vessels through the membrane calcium channels. Medications used for hypertension include several calcium channel blockers.

Potassium is also important to protect against calcification of blood vessels by preventing increased calcium entry into the cell. The mineral is also important for preventing high blood pressure/hypertension – in addition to excess sodium/salt, too little potassium can be a problem. See excerpt with the link. (29)

Five to nine servings of vegetables or fruits per day is the recommendation for a healthy balanced diet (five) or potentially cancer preventing diet (nine). They are a good source of potassium and magnesium in addition to other trace nutrients.

Cholesterol plaque formation (atherosclerotic plaques) along vessel membrane walls may be simply acting as a coating to prevent the electrically active calcium ions from entering cells or doing other damage by plastering it in place, like plaster or spackle on dry wall. Calcium and magnesium levels in normal health are very carefully controlled by the kidneys. Lack of potassium and excess sodium may also affect the kidneys ability to excrete excess calcium.

The current understanding of atherosclerosis does not describe the role of magnesium in this way – current description: (8) and (9).

The role of potassium, magnesium and calcium in hypertension is available here: (10) and (29).

Magnesium has been found to help reduce vascular calcification (atherosclerotic plaques in blood vessels) in animal based research, (11) {and I believe in a few human research studies too but I have to find the links again. See Table 7 for a list of symptoms common to magnesium deficiency, hypertension and myocardial infarction are included: (14)} Magnesium may also help reduce prostate cancer risk or progression, (15), and low magnesium levels may be an underlying factor in the formation of cancer tumors, (18); and depression (16) can be a symptom of magnesium deficiency (14) and frequently co-occurs with other diagnoses. (17)

The short story – excess calcium may increase heart disease risk while adequate iodine, selenium, magnesium, potassium and vitamin D are all important for a healthy pregnancy, ability to lactate for a longer duration and reduce the risk of heart disease and breast cancer.

Addition, miscarriage history and history of having more than four pregnancies/four children has been associated with increased risk of heart disease for the mothers. (12) Increased losses of iodine and magnesium stores from the bones may be an underlying factor.  Premature infants born to multiparous women (women who had previous pregnancies) are more likely to have low Thyroid Stimulating Factor – which is associated with hypothyroidism which can simply be due to low iodine levels during the pregnancy. (13)

The long story is in the links below;

except for references about magnesium, potassium and vitamin D for pregnancy and breast feeding but they are also important for pregnancy and lactation. The baby may not thrive or may be fussier if the breast milk is low in essential nutrients or it may be difficult to maintain an adequate supply if the woman is malnourished.

Disclaimer: Opinions are my own and the information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes. Thanks.

  1. Karl T. Weber, William B. Weglicki, Robert U. Simpson, Macro- and micronutrient dyshomeostasis in the adverse structural remodelling of myocardium, Cardiovasc Res. 2009 Feb 15; 81(3): 500–508. https://www.ncbi.nlm.nih.gov/pubmed/18835843 (1)
  2. Katherine Lindemann, Mothers who breastfeed may be less likely to suffer from heart disease and stroke later in life, an interview with Sanne A. E. Peters, University of Oxford, Research Fellow in Epidemiology, June 21, 2017, researchgate.net blog post,   https://www.researchgate.net/blog/post/breastfeeding-may-have-long-term-health-benefits-for-mothers-too  Benefits were seen/measured with six months increments in breastfeeding duration, with a large group of Chinese mothers, “Mothers who had breastfed their babies had a nine percent lower risk of heart disease and an eight percent lower risk of stroke.” (2)
  3. Loren Lipworth, L. Reness Bailey, Dimitrios Trichopoulos,

    History of Breast-Feeding in Relation to Breast Cancer Risk: a Review of the Epidemiologic Literature, JNCI: Journal of the National Cancer Institute, Volume 92, Issue 4, 16 February 2000, Pages 302–312, https://academic.oup.com/jnci/article/92/4/302/2624708 “Overall, the evidence with respect to “ever” breast-feeding remains inconclusive, with results indicating either no association or a rather weak protective effect against breast cancer. […] It appears that the protective effect, if any, of long-term breast-feeding is stronger among, or confined to, premenopausal women. It has been hypothesized that an apparently protective effect of breast-feeding may be due to elevated breast cancer risk among women who discontinue breast-feeding or who take medication to suppress lactation; however, the evidence is limited and should be interpreted with caution” (3)

  4. Angela M. Leung, MD, MSc, Elizabeth N. Pearce, MD, MSc,* and Lewis E. Braverman, MD, Iodine Nutrition in Pregnancy an Lactation, Endocrinol Metab Clin North Am. 2011 Dec; 40(4): 765–777. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3266621/  Iodine needs are increased during pregnancy and lactation and in iodine replete geographic areas breast milk levels seemed adequate for the infant’s needs. 250-290 micrograms is estimated to be needed compared to the RDA of 150 micrograms. That level did not seem adequate in geographically low area of New Zealand: ” In a recent study, the iodine needs for breastfed infants in iodine-deficient New Zealand remained inadequate even when their mothers were supplemented with 150 μg/d of iodine during the first 6 postpartum months.” (4)
  5. Peter PA Smyth, The Thyroid, Iodine and Breast Cancer, Breast Cancer Res. 2003; 5(5): 235–238.   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC314438/ Autoimmune thyroid disease and goiter is more common in patients with breast cancer. Iodine and selenium may be protective against both conditions, a review of literature rather than a study. (5)
  6. Heart Risk of High Protein Diets, June 4, 2018, The Hippocrtic Post,  https://www.hippocraticpost.com/ageing/heart-risk-of-high-protein-diets/?utm_source=website&utm_medium=webpush&utm_campaign=notifications The group of men with the highest intake of protein in percentage of total calories had increased risk of heart disease, except for protein from fish or eggs. “When they compared men who ate the most protein to those who ate the least, they found their risk of heart failure was:33 percent higher for all sources of protein;
    43 percent higher for animal protein;
    49 percent higher for dairy protein;
    17 percent higher for plant protein.” (6)
  7. Sherwin RS, Hendler RG, Felig P.,  Effect of Ketone Infusions on Amino Acid and Nitrogen Metabolism in Man. J Clin Invest. 1975 Jun;55(6):1382-90.
       https://www.ncbi.nlm.nih.gov/pubmed/1133179 (7)
  8. Isabella Albanese, Kashif Khan, Bianca Barratt, Hamood Al‐Kindi, Adel Schwertani, Atherosclerotic Calcification: Wnt is the Hint, Basic Science for Clinicians, February 8, 2018 Journal of the American Heart Association,  http://jaha.ahajournals.org/content/7/4/e007356 (8)
  9. The Cardiovascular System in Disease, Diseases of the Vessels, Chapter 6, Ch006-M3430.indd 4/19/2007, http://booksite.elsevier.com/samplechapters/9780723434306/9780723434306.pdf (9)
  10. Mark C. Houston MD, MS, Karen J. Harper MS, PharmD,  Potassium, Magnesium, and Calcium: Their Role in Both the Cause and Treatment of Hypertension, JCH, Vol 10, Issue 7, pp 3-11, July 2008,  https://onlinelibrary.wiley.com/doi/full/10.1111/j.1751-7176.2008.08575.x (10)
  11. Fatih Kircelli, Mirjam E. Peter, Ebru Sevinc Ok, Fatma Gul Celenk, Mumtaz Yilmaz, Sonja Steppan, Gulay Asci, Ercan Ok, Jutta Passlick-Deetjen, Magnesium reduces calcification in bovine vascular smooth muscle cells
    in a dose-dependent manner, Nephrol Dial Transplant (2012) 27: 514–521, https://watermark.silverchair.com/gfr321.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAZ0wggGZBgkqhkiG9w0BBwagggGKMIIBhgIBADCCAX8GCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMbSRHWigPf17i-jCnAgEQgIIBUIkKsm3S-WvD5qd-tNiIBBwsoiqBg-FrbTXdm2oS2q2AdX0wuviR-rsM-hi6IMVKWwMEinUYTbh7DopBg7SWLxBIi4bHXaQft3IHdQqhDKr_RiB69uxkVRwW_2aHFGYjR0FzhUSfhDrmVLweVHZRTIYDVbrSkgaVgLnFq4YHvxohG08oMbAeF4C26XL026jpA7J1xbOodHz_o5MUvoQgVcxwhrIFuu7ysxD_B7bjJehfrw6SLjkrm3Q43jrsS3vS37v_hIig_lTQyFCPe5L6UhFwlQvH1mwPIKPNituSvoob5OxY5odMFjtcXNg0Wz2tqLajbKP_Cg4Rt1X0c67CLvTGMkos_d7QLKbxwiFibtfpcrPJlIfbPPEIjd4jKRI2MWFePBaQTQLnUOoC934JHOp4abLCC5jRaOAgHykzJhZPOpvgmvrgj-jJmZBtfdgW9g (11)
  12. Kashmira Gander, Having More Kids Linked to Heart Disease Risk in Mothers, According to New Study, June 4, 2018, newsweek.com, http://www.newsweek.com/kids-linked-heart-disease-risk-mothers-according-new-study-956066 (12)

  13. Kelli K Ryckman, M.S., PhD, Cassandra N Spracklen, M.S., John M Dagle, M.D., PhD., Jeffrey C Murray, M.D., Maternal Factors and Complications of Preterm Birth Associated with Neonatal Thyroid Stimulating Hormone, J Pediatr Endocrinol Metab. 2014 Sep; 27(0): 929–938. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260397/ “Maternal and neonatal thyroid levels are tightly correlated and hypothyroidism …. Multiparous women had infants with lower TSH levels (P=8×10−4) compared to …” (13)

  14. R. Swaminathan, Magnesium Metabolism and Its Disorders, Clin Biochem Rev. 2003 May; 24(2): 47–66.   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1855626/ (14)

  15. Oseni, Saheed & Quiroz, Elsa & Kumi-Diaka, Jim. (2016). Chemopreventive Effects of Magnesium Chloride Supplementation on Hormone Independent Prostate Cancer Cells. Functional Foods in Health and Disease. 6. 1-15.  https://www.researchgate.net/publication/291164181_Chemopreventive_Effects_of_Magnesium_Chloride_Supplementation_on_Hormone_Independent_Prostate_Cancer_Cells (15)

  16. Eby GA, Eby KL, Rapid recovery from major depression using magnesium treatment., Med Hypotheses. 2006;67(2):362-70. Epub 2006 Mar 20. https://www.ncbi.nlm.nih.gov/pubmed/16542786 (16) 

  17. Hee-Ju Kang, Seon-Young Kim, Kyung-Yeol Bae, Sung-Wan Kim, Il-Seon Shin, Jin-Sang Yoon, and Jae-Min Kim, Comorbidity of Depression with Physical Disorders: Research ad Clinical Implications, Chonnam Med J. 2015 Apr; 51(1): 8–18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4406996/ (17)
  18. : Castiglioni S, Maier JAM. Magnesium and cancer: a dangerous liason. Magnes Res 2011; 24(3): S92-S100 doi:10.1684/mrh.2011.0285   http://www.mgwater.com/Magnesium%20and%20Cancer.pdf (18)
  19.  Pharmacology of Cardiac Potassium Channels, Cardiovascular Research, Volume 62, Issue 1, 1 April 2004, Pages 9–33, Oxford Academic – see Table 4, https://academic.oup.com/cardiovascres/article/62/1/9/373105 (19)
  20. Lakshman Goonetilleke, John Quayle, TREK-1 K+ Channels in the Cardiovascular System: Their Significance and Potential as a Therapeutic Target, Cardiovascular Therapeutics 30 (2012) e23–e29  https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1755-5922.2010.00227.x (20)
  21. University of Pittsburgh: Cardiovascular system during the postpartum state in women with a history of preeclampsia, Chapter 2: Cardiovascular System,  pp 190-191, Advances in Physiology Research and Application: 2012 Edition, Scholarly Editions, Dec 26, 2012, ebook, https://books.google.com/books?id=3SyvNMZLBU0C&pg=PA190&lpg=PA190&dq=TREK+1+preeclampsia&source=bl&ots=2SzKQHcFJ0&sig=fGwDeK6cMIkUXhtwPDNKqio1zIQ&hl=en&sa=X&ved=0ahUKEwirhN_h6-XbAhUSbq0KHWDZCS0Q6AEIUjAF#v=onepage&q=TREK%201%20preeclampsia&f=false (21)
  22. Ma R, Seifi M, Papanikolaou M, Brown JF, Swinny JD, Lewis A.TREK-1 Channel Expression in Smooth Muscle as a Target for Regulating Murine Intestinal Contractility: Therapeutic Implications for Motility Disorders.  Front Physiol. 2018 Mar 6;9:157, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5845753/ (22)
  23. Antidepressant Drugs Suppress Activity of Potassium Channels, Lawrence Berkeley National Laboratory, Feb. 8, 2011, psypost.org,  https://www.psypost.org/2011/02/antidepressant-ssri-potassium-channel-4068 (23)
  24. Nicholas J. Talley, SSRIs in IBS: Sensing a dash of disappointment. Clinical Gastroenterology and Hepatology, May 2003, Volume 1, Issue 3, Pages 155–159.  https://www.cghjournal.org/article/S1542-3565(03)70030-5/fulltext (24)
  25. Tülay Özkan Seyhan, Olgaç Bezen, Mukadder Orhan Sungur, İbrahim Kalelioğlu, Meltem Karadeniz, and Kemalettin Koltka,

    Magnesium Therapy in Pre-eclampsia Prolongs Analgesia Following Spinal Anaesthesia with Fentanyl and Bupivacaine: An Observational Study., Balkan Med J. 2014 Jun; 31(2): 143–148.   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4115934/ Exerimental group needed less fluid replacement and waited longer before requesting additional pain killing medication than the women with normal (no preeclampsia) deliveries. (25)

  26. Ramanathan J, Vaddadi AK, Arheart KL. Combined spinal and epidural anesthesia with low doses of intrathecal bupivacaine in women with severe preeclampsia: a preliminary report. Reg Anesth Pain Med. 2001 Jan-Feb;26(1):46-51. https://www.ncbi.nlm.nih.gov/pubmed/11172511 (26)

  27. KCNK2 potassium two pore domain channel subfamily K member 2 [ Homo sapiens (human) ], Gene ID: 3776, updated on 23-May-2018,   https://www.ncbi.nlm.nih.gov/gene/3776 (27)

     

  28. Tayyba Y Ali, Fiona Broughton Pipkin, and Raheela N Khan, The Effect of pH and Ion Channel Modulators on Human Placental Arteries. PLoS One. 2014; 9(12): e114405. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260857/  “In vessels isolated from placentae of women with pre-eclampsia (n = 6), pH responses were attenuated.” (28) *attenuated means a weakened response, less responsive to the stimulus.
  29. Qi Qian, Dietary Influence on Body Fluid Acid-Base and Volume Balance: The Deleterious “Norm” Furthers and Cloaks Subclinical Pathophysiology, Nutrients 2018, 10(6), 778; Open Access, http://www.mdpi.com/2072-6643/10/6/778/htm “Recently, Sun et al. [53] demonstrated a causal role for dietary K+ in the regulation of osteogenic differentiation and calcification of vascular smooth muscle cells, both in vitro and in atherosclerotic animal models. Specifically, lower levels of extracellular fluid K+ induce vascular smooth muscle cell osteogenic transformation by elevating intracellular calcium. The latter activates CREB (cyclic AMP response element-binding protein) leading to an enhanced expression of osteogenic markers, e.g., RUNX-2, and simultaneously reduced smooth muscle cell markers, e.g., α-actin. Remarkably, even a slight serum K+ reduction (mean K+ level, 3.70 ± 0.21 mEq/L) in mice can trigger significant vessel calcification associated with elevated pulse-wave velocity, a reliable indicator of aortic stiffness. On the contrary, when K+ levels are raised to ~4.73 mEq/L by dietary modification, signs of osteogenic differentiation were abrogated, and vascular calcification prevented. Consistent with the notion of K+ being protective to vasculature, a high ratio of urine Na+/K+ excretion (indicative of high Na and low K+ intake) has recently been linked to the genesis of HTN [54].?” (29)
  30.  Robert Vink, Mihai Nechifor, editors, Magnesium in the Central Nervous System, University of Adelaide Press, 2011, adelaide.edu.au, free ebook pdf, https://www.adelaide.edu.au/press/titles/magnesium/magnesium-ebook.pdf  See page 20 re TRPM7 channels and different effects of oxidative stress on calcium versus magnesium being allowed through the ion channel. Magnesium helps survival while calcium can increase risk to the cell.  other notes about the book:   https://twitter.com/deNutrients/status/1012685811001806849?s=19
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Calcification of soft tissue – hardening organs and softening bone

     Vascular calcification is better known as atherosclerosis. Cholesterol plaques in blood vessels are generally a mixture of calcium with the fat. Calcification also occurs in arthritis as bone spurs and calcium can collect in organs and glands and impair their function. The pineal gland is very tiny and located within the brain. It it responsible for the melatonin hormone that helps us sleep. A calcified pineal gland no longer helps with sleep but the condition may be reversible by limiting intake of calcium and increasing intake of magnesium.     Reversing calcification may start with reducing calcium intake. The following article mentions a link between higher intake of calcium and worsening of coronary artery calcification and numbers of deaths within a group of end stage renal disease patients. Magnesium is wasted by healthy kidneys and little is recycled/reclaimed the way calcium and sodium are conserved by healthy kidneys – add end stage renal disease and magnesium is leaking out faster then intestinal absorption can occur even if the magnesium was in the food or drink or supplement.

Calcium can not make strong bones if nothing is keeping it from leaking out in response to the stress chemicals’ fight or flight messages. People suffer from osteoporosis and weak bones along with hardening of the arteries and organs –  excess calcium and vitamin D might be part of the problem. Too much active vitamin D can add to calcium imbalance because it signals the bones to let go of stored calcium and magnesium.

The minerals are also released during stress reactions in case there is a need to run from danger or heal a wound. White blood cells around wounds have the enzyme needed to activate vitamin D to the hormone form.

What do you know – it is important to mellow out and de-stress to help keep bone tissue hard and organ tissue soft.

  1. [jasn.asnjournals.org/content/15/12/2959.full] Vascular Calcification Mechanisms, by Cecilia M. Giachelli, doi: 10.1097/01.ASN.0000145894.57533.C4 JASN December 1, 2004 vol. 15 no. 12 2959-2964

“In a landmark study, Goodman et al. (24)  found that coronary artery calcification occurred in young patients with ESRD (end stage renal disease) decades before this pathology was observed in the normal population. Furthermore, progression of vascular calcification in this group was positively correlated with serum P levels, Ca x P, and daily intake of Ca (24).”

***Vascular calcification has been correlated to higher intakes of calcium and phosphorus in this research article. Cardiovascular deaths are common among end stage renal disease and/or diabetic patients – I suggest they should be limiting calcium and phosphorus and increasing their magnesium intake in order to reduce risks of calcium overload. In the average human the kidneys favor calcium absorption and retention and waste magnesium.
Over the course of mankind the body adapted to a food and water supply that was abundant in magnesium and limited in calcium content. Calcium is important for strong bones but only in combination with other nutrients. Vitamin K (brown rice, green leafy vegetables and good guy bacteria in our intestines are sources) is essential for blood clotting and for healthy bones. Strontium is a trace mineral that may be essential to healthy bones and of course magnesium is the trace mineral that helps keep calcium inside of the bone where it belongs. Excessive levels of active vitamin D tell the bone to release the stored minerals. Active vitamin D (a very strong steroid based hormone in actuality) can switch on and off 900+ genes.
The study found (unsurprisingly) that the end stage renal disease patients who were treated with the typical phosphate binding medications that contained calcium had 28% progression of calcification compared to the experimental group who were given a phosphate binding agent that didn’t contain calcium. [12]

Let’s keep the calcium in the bone tissue where it belongs.

The article Vascular Calcification Mechanisms [1] presents four potential ways the soft tissue calcification may develop.

“First, human and mouse genetic findings have determined that blood vessels normally express inhibitors of mineralization, such as pyrophosphate and matrix gla protein, respectively, and that lack of these molecules (“loss of inhibition”) leads to spontaneous vascular calcification and increased mortality (10,29).”

Second – genetic/phontypic changes leading to production of bone proteins within the blood vessel may occur (the blood vessel cell switches on bone cell mechanisms).

“Third, bone turnover leading to release of circulating nucleational complexes has been proposed to explain the link between vascular calcification and osteoporosis in postmenopausal women (41–43).”

“Fourth, cell death can provide phospholipid-rich membranous debris and apoptotic bodies that may serve to nucleate apatite, especially in diseases where necrosis and apoptosis are prevalent, such as atherosclerosis (34,44,45).”

*** Magnesium deficiency could effect the enzyme production necessary for producing the “inhibitors” of bone formation produced in functioning blood vessels. Magnesium is crucial to over 300 enzymes. It is also essential for the growth of healthy white blood cells. A plentiful supply of white blood cells would engulf waste products of apoptosis and the dead cell material wouldn’t be left messing up vessel walls. Chronic magnesium deficiency will promote bone turnover in order to access the stored magnesium found within. Long term kidney problems may be reducing the amount of magnesium that the body can retain and further through off the calcium/magnesium balance.
Chronically elevated active D would chronically cause demineralization of the bones and also might be switching on and off genes in areas of the body (blood vessels for example) that shouldn’t be forming bone tissue. I would be very curious what the end stage renal disease patients’ 1, 25 D levels (hormone) are compared to their 25 D levels (vitamin).  My 1, 25 D levels have been at the high end of normal and 25 D levels below normal (“deficient”) for five years of testing. I have been actively avoiding supplements and foods with vitamin D and much time in the sun during that time because I have found it reduces my symptoms of  muscle knots (fibromyalgia), I also have taken magnesium supplements regularly.
A 200-500 mg supplement taken along with food generally will not cause the smooth muscles of the intestines to relax into a sudden bowel movement. Magnesium supplements are non-toxic but if absorbed too rapidly can cause too much muscle relaxation in the bowels or heart. Fluttery weak heart beats may result if you hang out in an Epsom salt bath for a long time due to the relaxation of too many of the muscle fibers at the same time. Magnesium taken with food or in the glycinate form does’t seem to have the over relaxing effect on the bowels.
Magnesium helps keep the calcium in the bone and out of the soft tissue. Use the calcium channel blocker that Mother Nature provided – magnesium. Eat more nuts, beans, seeds, green leafy vegetables. and chocolate every day for strong bones and soft organs!
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Disclaimer: Opinions are my own and the information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes.

Reference List

From Vitamin D bibliography [link]:

10. Rutsch F, Ruf N, Vaingankar S, Toliat MR, Suk A, Hohne W, Schauer G, Lehmann M, Roscioli T, Schnabel D, Epplen JT, Knisely A, Superti-Furga A, McGill J, Filippone M, Sinaiko AR, Vallance H, Hinrichs B, Smith W, Ferre M, Terkeltaub R, Nurnberg P: Mutations in ENPP1 are associated with “idiopathic” infantile arterial calcification. Nat Genet 34: 379–381, 2003[CrossRef][Medline]
12. Sangiorgi G, Rumberger JA, Severson A, Edwards WD, Gregoire J, Fitzpatrick LA, Schwartz RS: Arterial calcification and not lumen stenosis is highly correlated with atherosclerotic plaque burden in humans: A histologic study of 723 coronary artery segments using nondecalcifying methodology. J Am Coll Cardiol 31: 126–133, 1998[Abstract/Free Full Text]

29. Luo G DP, McKee MD, Pinero GJ, Loyer E, Behringer RR, and Karsenty: G Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. Nature 386(March 6): 78–81, 1997[CrossRef][Medline]

34. Tanimura A, McGregor DH, Anderson HC: Matrix vesicles in atherosclerotic calcification. Proc Soc Exp Biol Med 172: 173–177, 1983[CrossRef][Medline]

  1. Price PA, Caputo JM, Williamson MK: Bone origin of the serum complex of calcium, phosphate, fetuin, and matrix Gla protein: Biochemical evidence for the cancellous bone-remodeling compartment. J Bone Miner Res 17: 1171–1179, 2002[CrossRef][Medline]
  2. Price PA, Faus SA, Williamson MK: Bisphosphonates alendronate and ibandronate inhibit artery calcification at doses comparable to those that inhibit bone resorption. Arterioscler Thromb Vasc Biol 21: 817–824, 2001[Abstract/Free Full Text]
  3. Price PA, June HH, Buckley JR, Williamson MK: Osteoprotegerin inhibits artery calcification induced by warfarin and by vitamin D. Arterioscler Thromb Vasc Biol 21: 1610–1616, 2001[Abstract/Free Full Text]
  4. Proudfoot D, Skepper JN, Hegyi L, Bennett MR, Shanahan CM, Weissberg PL: Apoptosis regulates human vascular calcification in vitro: Evidence for initiation of vascular calcification by apoptotic bodies. Circ Res 87: 1055–1062, 2000[Abstract/Free Full Text]
  5. Schoen FJ, Tsao JW, Levy RJ: Calcification of bovine pericardium used in cardiac valve bioprostheses. Am J Pathol 123: 134–145, 1986[Abstract]
  • [ajsonline.org/cgi/content/full/305/6-8/661] Nita Sahai, Modeling apatite nucleation in the human body and in the geochemical environment American Journal of Science, Vol. 305, June/September/October 2005, P.661-672; doi:10.2475/ajs.305.6-8.661

“Magnesium inhibits nucleation by adsorbing faster than calcium, as an outer-sphere surface complex, at the active site.”