Tag Archives: hypercalcemia

Links about magnesium deficiency and Substance P, a neuropeptide associated with inflammation

Magnesium is Essential for Preventing Substance P Overload , May 24, 2011, by Byron J. Richards, Board Certified Clinical Nutritionist , “Substance P is a neuropeptide that is typically ”over-heated” in situations of anxiety, depression, digestive bloating, insomnia, fibromyalgia, PTSD, and cardiovascular deterioration. New research shows that one of the first signs of magnesium deficiency1 is that it enables the over-production of substance P.” Read More:  [http://www.wellnessresources.com/health/articles/magnesium_is_essential_for_preventing_substance_p_overload/]

Raw shelled pumpkin seeds are a good source of magnesium, zinc, B vitamins and essential fatty acids. A few prenatal clients that I have worked with in the past, who were high risk due to a history of high blood pressure or pre-eclampsia during their first pregnancy, did report that the raw shelled pumpkin seeds that I had recommended they try adding to their diet during their second pregnancy did seem helpful for preventing high blood pressure or pre-eclampsia from reoccurring.  So it is also possible that raw unsalted pumpkin seeds may be a beneficial food for use during the perinatal stage for women who hope to prevent autism from developing in their infant during conception or the early weeks of pregnancy. [http://transcendingsquare.com/2014/07/24/magnesium-might-help-protect-against-beta-amyloid-placques/]

/Disclosure: This 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./

Additional notes to think more about later:

  1. Gehan A Mostafa; Laila Y AL-Ayadhi, The Possible Link Between the Elevated Serum Levels of Neurokinin A and Anti-ribosomal P Protein Antibodies in Children with Autism, J Neuroinflammation. 2011;8(180) Excerpt from the background section: “Neurogenic inflammation is orchestrated by a large number of neuropeptides. Tachykinins (substance P, neurokinin A and neurokinin B) are pro-inflammatory neuropeptides that may play an important role in some autoimmune neuroinflammatory diseases. Autoimmunity may have a role in the pathogenesis of autism in some patients.” And an excerpt from the discussion section: “In our series, increased serum levels of anti-ribosomal P protein antibodies were found in 44.3% of autistic patients. This study was the first to investigate serum levels of anti-ribosomal P protein antibodies in autistic children.” [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3261830/]
  2. Julio Hernandez, et. al., Substance P Is Responsible for Physiological Alterations Such as Increased Chloride Ion Secretion and Glucose Malabsorption in CryptosporidiosisInfect. Immun. March 2007 vol. 75 no. 3 1137-1143
    [http://iai.asm.org/content/75/3/1137.full] *Cryptosporidiosis is a parasitic infection that can be more of a risk for AIDS patients than for average people — reason unknown — The reason speculatively might be that there is a magnesium deficiency or an elevated calcium level resulting from elevated hormone D levels underlying the increased risk for crypotosporidiosis in AIDS patients.
  3. Sylke Müller1 and Barbara Kappes, Vitamin and co-factor biosynthesis pathways in Plasmodium and other apicomplexan parasitesTrends Parasitol. 2007 Mar; 23(3): 112–121.
    This article is primarily about a few B vitamins and protozoan parasites but one section addresses vitamin D, Excerpt: “One way in which vitamin D3 might affect Plasmodium is through its involvement in phospholipid metabolism and signalling pathways 60. Vitamin D3 and analogues have pronounced inhibitory effects on P. falciparum erythrocytic late stage development possibly because the phospholipid biosynthesis pathways of the parasite is affected by these compounds 61. Inhibition of phospholipid biosynthesis by other classes of inhibitors (for instance choline analogues) has been followed up extensively 62, 63 and it is likely that these inhibitors will be developed as new drugs against malaria in the near future 64. Thus the activity of vitamin D3 analogues merits further attention.” [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2330093/]
  4. 60. Boyan BD, et al. 1,25-(OH)2D3 modulates growth plate chondrocytes via membrane receptor-mediated protein kinase C by a mechanism that involves changes in phospholipid metabolism and the action of arachidonic acid and PGE2. Steroids. 1999;64:129–136. [PubMed] *Roughly this title could be translated into: Hormone D affects growth plate cartilage cells by affecting the endogenous cannabinoid system, — arachidonic acid and PGE2 can be formed from cannabinoids that are released from storage within cell membranes. Elevated levels of calcium intracellularly can be a trigger signalling the release of endogenous cannbinoids from the membranes.
  5. 7. Regulation of growth plate chondrocytes and bone cells,                                        Excerpt: “In recent years it has been demonstrated that a large number of growth factors and cytokines regulate the proliferation and differentiation of bone and cartilage cells in vitro and in vivo (Table 2). This subject has been extensively reviewed (Goldring & Goldring, 1990; Canalis, McCarthy & Centrella, 1988a; Price & Russell, 1992; Martin, 1989). There is also increasing evidence that abnormal production of cytokines in diseases such as rheumatoid arthritis, osteoarthritis and osteoporosis may result in inappropriate responses by bone and cartilage cells. Those cytokines and growth factors considered to be of particular importance during bone development and growth include the IGFs, TGF a and b, bone morphogenetic proteins (BMPs), FGF, PDGF and epidermal growth factor (EGF). Many of the cell types present in the microenvironment of growing bone contribute to the local synthesis of cytokines and growth factors including the resident endothelial cells, marrow stromal cells, osteoblasts, periosteal cells and chondrocytes. The haemopoetic cells present in bone marrow include circulating monocytes, macrophages and T cells; these are another potential source of cytokines. In fact, several lines of evidence point to there being a close relationship between bone cells and cells of the immune system (Skjodt & Russell, 1993).”

    7.12. Parathyroid hormone related peptide (PTHrP)

    “PTHrP is a peptide closely related to PTH that is produced by normal tissues, with similar effects to PTH on bone. It has been established as having an important role in regulating the hypercalcaemia that is associated with some malignancies (Webb et al., 1988). PTHrP has also been identified as a fetal hormone which may regulate placental calcium (Ca2+) flux (Orloff, 1989). This peptide may also have an important role in skeletal development, having been localised in embryonic bone, and a recent study has shown that mice with a defective PTHrP gene have multiple skeletal abnormalities (Karaplis et al., 1992).” [http://archive.unu.edu/unupress/food2/UID06E/UID06E0V.HTM]

  6. Arnold J. Felsenfeld, et. al., Dynamics of Parathyroid Hormone Secretion in Health and Secondary HyperparathyroidismCJASN November 2007 vol. 2no. 6 1283-1305 [http://cjasn.asnjournals.org/content/2/6/1283.full]

  7. S. C. Kukreja, et. al., Antibodies to parathyroid hormone-related protein lower serum calcium in athymic mouse models of malignancy-associated hypercalcemia due to human tumors. J Clin Invest. 1988 Nov; 82(5): 1798–1802 [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC442751/] Abstract: “A parathyroid hormone-related protein (PTHrP) has recently been isolated from tumors associated with hypercalcemia. In the present study, we tested the effects of neutralizing antisera to the PTHrP on serum calcium and urine cAMP in two animal models of malignancy-associated hypercalcemia. The animal models consisted of (a) a human squamous cell lung cancer and (b) a human laryngeal cancer, both serially carried in athymic mice. The antisera specifically reduced the elevated serum calcium and urinary cAMP levels in the tumor-bearing animals. We conclude that PTHrP plays a major role in the pathogenesis of malignancy-associated hypercalcemia.”

  8. Moniz C., et. al., Parathyroid hormone-related peptide in normal human fetal development., J Mol Endocrinol. 1990 Dec;5(3):259-66. [http://www.ncbi.nlm.nih.gov/pubmed/2288637Abstract:

    “Parathyroid hormone-related peptide (PTHrP) has been detected in fetal serum and amniotic fluid. Using a combination of immunocytochemistry and molecular biology we have detected the peptide and its mRNA in a variety of fetal tissues throughout gestation. Tissue-specific mRNA isoforms were observed, the pattern of hybridization of which changed throughout gestation. In addition, the intensity and pattern of immunocytochemical localization of the peptide was found to vary over the time-period studied (8-30 weeks). PTHrP is expressed by a variety of tumours associated with the syndrome of humoral hypercalcaemia of malignancy and probably accounts for the hypercalcaemia by virtue of its limited amino acid homology with parathyroid hormone. These data demonstrate for the first time that PTHrP, a tumour-related peptide, is expressed during normal human fetal development, and suggest the possibility that it may function to regulate fetal calcium balance and growth in utero.”


  9. “Parathyroid hormone-related peptide (PTHrP) can be elevated in pregnant and lactating women and in newborn infants. Nonmalignant conditions that have been described in association with elevated plasma PTHrP levels include systemic lupus erythematosus, HIV-associated lymphadenopathy, lymphedema of chest or pleural cavities, and with benign tumors of the ovary, kidney and the neuroendocrine system.” [http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/81774]
  10. Shane T. Mortimer, David A. Hanley, William K. Stell, Immunohistochemical identification of calcitonin gene-related peptide and substance P in nerves of the bovine parathyroid gland., Cell and Tissue Research
    , Volume 261, Issue 2, pp 339-345, [http://link.springer.com/article/10.1007/BF00318675Summary:

    “Although peptide neurotransmitters have been shown to modulate hormone secretion in many glands, there are very few studies of neurotransmitters in the parathyroid gland. Bovine parathyroid glands were collected at a local abattoir, fixed with paraformaldehyde, sectioned using a cryostat, and stained by indirect immunohistochemistry for calcitonin gene-related peptide and substance P. We were able to positively identify both neuropeptides. Nerve fibres containing calcitonin gene-related peptide and substance P were identified in contact with the tunica media of arteries and arterioles and dispersed throughout the stroma of the gland. While many of the fibres encircled parenchymal lobules, no intimate contact with the peripheral chief cells was observed. All immunoreactive fibres were found to contain both neuropeptides. Since calcitonin gene-related peptide and substance P are vasodilators, they may increase blood flow within the gland. In addition, the neuropeptides may diffuse from perilobular nerve fibres into the parenchyma, thereby modulating secretion of parathyroid hormone.”

  11. And for the swish and score — calcitonin gene-related peptide is associated with migraine attacks — hmmmmm — health is a miracle when it works. [https://migraine.com/blog/what-is-calcitonin-gene-related-peptide-cgrp/]

Calciphylaxis may be caused by several different nutrient issues

Calciphylaxis usually includes an imbalance of calcium and phosphate and a deficiency of protein C may also be involved. Protein C deficiency may be caused by genetic or acquired reasons. Protein C is involved in blood clotting. Vascular and soft tissue calcification frequently is also present in patients with calciphylaxis symptoms. The mineral content of the calciphylaxis sores has been found to resemble the mineral balance of bone.

Imbalance in vitamin D and hormone D metabolism might affect magnesium levels in some unusual cases and may promote intestinal malabsorption of magnesium. However elevated magnesium is more typically found in patients who have calciphylaxis as a side effect of dialysis in end stage renal disease. The kidney disease causes an abnormal lack of hormone D because the kidneys in normal health are the only place where vitamin D is activated into the hormone D form.

These are copies of links that I was reading and Tweeted last night:

  1. Mineral substance of bone tissue and of experimental cutaneous calcinosis in rats: chemical analysis and ESR study.
  2. Calciphylaxis assoc w cholangiocarcinoma… /heparin & vit K didn’t help/ Thrombosis & protein C deficiency involved/
  3. Retrospective analysis of tissue plasminogen activator as an adjuvant treatment for calciphylaxis. /Ca P homeostasis/
  4. Calciphylaxis… “the reported median survival time is 2.6 months after diagnosis,”
  5. Aggressive calciphylaxis in end-stage renal disease… /assoc w vascular & soft tissue calcification/
  6. Calciphylaxis is a cutaneous process without involvement of internal organs… /assoc w vascular calcification/
  7. Net-like pattern of calcification on plain soft-tissue radiographs in patients with calciphylaxis. – PubMed – NCBI
  8. Is calciphylaxis best treated surgically or medically? – PubMed – NCBI
  9. Calciphylaxis in a morbidly obese woman w RA presenting w severe weight loss & vit D def. /pamidronate & D tx worked/
  10. Calciphylaxis in the absence of end-stage renal disease. – PubMed – NCBI /low vit D but tx surgery/
  11. The surgical management of renal hyperparathyroidism. – PubMed – NCBI
  12. Secondary hyperparathyroidism in children with chronic renal failure: pathogenesis and treatment. – PubMed – NCBI
  13. Vitamin D, parathyroid hormone, and acroosteolysis in systemic sclerosis. /low 25D w 2ndary hyperPTH in sunny climate

  14. Bone metabolism in celiac disease. – /following gluten free diet for 6 mo normalized 25D, calcium & PTH levels/

  15. Hypomagnesemia. Suppression of secondary hyperparathyroidism in chronic renal failure. – PubMed – NCBI

  16. Magnesium deficiency: possible role in osteoporosis associated with gluten-sensitive enteropathy. – PubMed – NCBI
  17. Recent data on magnesium & osteoporosis. “Mg def in post-menopausal osteoporosis, prob caused by Mg malabsorption.”
  18. [The significance of magnesium in medicine. (II) Disturbances of Mg metabolism & their treatment (author’s transl)].
  19. Metabolic disorders of cattle. /pellagra discussed, zinc, B6 Cu Mg def, malabsorption, iron overload can deplete B3/

Why do I care? because even though my symptoms are unusual I feel that I still deserve individualized health care. As a dietitian I was taught to look up information about any unusual diagnoses that patients might have and to provide individualized guidance if available or provide background information to help patients be able to make more informed choices about their treatment plan.

I also care because I think women deserve individualized healthcare even if we may get emotional or moody. Physical and mental illness symptoms can be related to underlying issues and simply medicating a symptom not only fails to address the underlying issue but it also fails to look for an underlying issue which can be life threatening if care is delayed in acute situations:

Whether male or female in a for-profit health industry being your own patient advocate or hiring a professional patient advocate may be life saving when navigating the increasingly complex health care system.

See the previous post for my own patient struggles with symptoms of hyperparathyroidism and calciphylaxis like sores: Secondary hyperparathyroidism and calciphylaxis symptoms; an update with lab values

/Disclosure: This 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./