Calcium in the Body: It's About Much More than Bones

When your patients think of calcium, they think of supplementing the supply of calcium in their food to make sure they have strong and healthy bones. Understandably so.

The airwaves are inundated with the message, along with what prescription medications to take when their efforts fall short. Less appreciated by the public and by many healthcare professionals is the critical role calcium plays at the intracellular level in key cell chemistry and function.

SERCA and PMCA

Two related enzymes, Sarcoplasmic Reticulum Ca2+ ATPase (SERCA), and Plasma Membrane Ca2+ATPase (PMCA) play vital roles in the regulation of calcium ion location and concentration in the cell, and each have significant impact on cellular, systemic, and ultimately patient health.

Though both are critically important to health and vitality, SERCA has a more immediate role for a chiropractic patient presenting with subluxation. When a muscle fiber contracts, a calcium ion is released from the sarcoplasmic reticulum (SR) to the cytoplasm. SERCA is responsible for returning a calcium ion to the SR so the muscle fiber can relax the contraction and return to the ready position to contract again.

As the supply of this enzyme is used up, the muscle fiber fatigues and then exhausts, unable to recover for another contraction and predominantly resulting in its remaining locked in the contracted state. Practically speaking, Chiropractic deals with the effects of a shortage of SERCA in the clinic on a daily basis. The small stability and control musculature of the spine, specifically the rotatores, intertransversarii, interspinales, and the larger multifidus, are particularly susceptible to exhaustion of SERCA supplies in subluxation conditions.

As with all skeletal musculature, progressive fatigue states in these muscles result in fixation in the contracted state until the supply of the SERCA enzyme is restored. In the acute stage of subluxation, this may work to the benefit of the patient by stabilizing the affected vertebrae to limit further damage to nerve tissues.

However, in the subacute and chronic stages, lingering enzyme insufficiencies coupled with habituated neuromuscular signaling work at cross purposes with the doctor's efforts to resolve the subluxation. Supplementation to address the Ca2+ATPase shortfall allows the soft tissues to respond dynamically and appropriately to Chiropractic care resulting in more effective patient treatments and greater actual and perceived benefit.

The second type of enzyme, PMCA, is in the cell membrane of every cell in the body and regulates calcium ion levels inside the cell. When calcium ions, which carry a positive charge, become too numerous in the cell from intracellular chemical reactions, cell signaling and cell health and reproduction are compromised. Increases in this key enzyme help return calcium to optimal intracellular levels, improve overall cell health and function, and speed recovery of soft tissue injuries.

This is of particular importance to those patients that have sustained a spinal cord injury.

[pb]Spinal Cord Injury Recovery

After a spinal cord injury, the expression of PMCA is decreased. The inhibition of PMCA delays calcium clearance, increases the number of immunoreactive cells, and induces swelling and beading of SMI-32-positive neurites which in turn causes neuronal damage and loss in the spinal cord. A great deal of secondary spinal cord injury is a result. In almost all cases, the reduction of PMCA is coincident with the onset of clinical symptoms.

Intracellular calcium levels are involved in all types of inflammatory response. Inflammation occurs when the body produces one or more pro-inflammatory mediators such as leukotreines, MCP-1, and histamine in response to an injury or other triggering event. The release of leukotriene, MCP-1 and histamine are determined by levels of intracellular calcium in mast cells. When intracellular calcium reaches excessive levels, the inflammatory response is triggered. It should be noted that pain levels correlate with leukotriene levels in particular.

Ca2+ATPase, both SERCA and PMCA, helps maintain optimal levels of intracellular calcium thus reducing inflammation and pain. It is interesting to note that prescription steroids, a mainstay of treating inflammation in both oral form and as corticosteroid injections, stimulate Ca2+ATPase to reduce inflammatory conditions, albeit with well understood side effects. Acupuncture (without notable side effects) also stimulates Ca2+ATPase in treated muscle to improve recovery.

Adequate levels of SERCA are important to enable postural and locomotor muscles to respond to treatment, and that adequate levels of PMCA are important to prevent secondary damage after spinal cord injury and nerve tissue trauma due to inflammation. It is clear that optimizing the body's ability to produce Ca2+ATPase is an important factor in treating patients. Certain botanical supplements, including jasmine flower extract, green tea, gingerol, and astragalus, have demonstrated stimulatory effects on Ca2+ATPase.

Appropriate supplementation can significantly improve treatment outcomes, and the addition of a high quality botanical supplement to optimize Ca2+ATPase is an important consideration in a comprehensive plan of care.

Recognizing Deficiencies

How do you recognize a correctable deficiency in Ca2+ATPase that demonstrates the need for supplementation?

While many vitamin, mineral or enzyme deficiencies are best determined through routine blood testing, a Ca2+ATPasae deficiency is much more straightforward; if he or she have presented in your office with an injury, your patient is, at the very least, locally deficient in this regulatory enzyme, as explained above. In addition to the suppression of this enzyme in tissues surrounding the injury site, lifestyle, the aging process, and environmental toxins are direct contributors to decline or suppression in our body's production of Ca2+ATPase.

Research demonstrates that production of this key regulatory enzyme declines in many tissues throughout the body, including the brain, the heart, the blood vessels, the bladder, and the skeletal muscles. Reduced Ca2+ATPase levels play a major role in age-related diseases such as Alzheimer's, heart failure, high blood pressure, muscle weakness and bladder problems.

In addition to age-related declines, temporary or long-term lifestyle factors such as a high cholesterol diet, alcohol over-consumption, smoking, the abuse of recreational drugs, and periods of high stress directly suppress the production of Ca2+ATPase. Also, numerous environmental toxins inhibit the enzyme. These include mercury, lead, fluoride, aluminum, pesticides, electromagnetic fields, radiation and second hand smoke. Food dyes, artificial flavoring and preservatives such as BHT and Bis-phenol also inhibit production. Ca2+Atpase is crucial for optimal health and specific supplementation can help offset the toxic exposure you and your patients encounter every day.

[pb]Bottomlines

There are two bottom lines for you, as a good Chiropractor. First and most important is a successful outcome for your patients. Your best efforts while attending to a patient's needs through soft tissue and osseous manipulation can be enhanced through the knowledgeable addition of supplementation to their plan of care. Specific supplementation to improve the body's ability to produce optimal levels of Ca2+ATPase, a key calcium regulating enzyme, will certainly benefit your principal goal. Second, you must consider your financial bottom line to insure you remain viable as a Chiropractor and available to your patients for years to come. Recommending high quality, well researched supplements and making them available to your patients in your office not only contributes positively to your financial bottom line, it is a clear indication to each of your patients that you are engaged and invested in optimizing and maintaining their health and wellbeing. That is a long-term investment in both bottom lines.

References

• Altered sarcoplasmic reticulum function in rat diaphragm after high-intensity exercise.
  Matsunaga S, Inashima S, Tsuchimochi H, Yamada T, Hazama T, Wada M.
  Acta Physiol Scand. 2002 Nov;176(3):227-32.
  PMID: 12392502 [PubMed - indexed for MEDLINE]
• Effects of fatigue and training on sarcoplasmic reticulum Ca(2+) regulation in human skeletal muscle.
  Li JL, Wang XN, Fraser SF, Carey MF, Wrigley TV, McKenna MJ.
  J Appl Physiol. 2002 Mar;92(3):912-22.
  PMID: 11842021 [PubMed - indexed for MEDLINE] Free Article
• Prolonged exercise induces structural changes in SR Ca(2+)-ATPase of rat muscle.
  Luckin KA, Favero TG, Klug GA.
  Biochem Med Metab Biol. 1991 Dec;46(3):391-405.
  PMID: 1838929 [PubMed - indexed for MEDLINE]
• Altered sarcoplasmic reticulum function after high-intensity exercise.
  Byrd SK, McCutcheon LJ, Hodgson DR, Gollnick PD.
  J Appl Physiol. 1989 Nov;67(5):2072-7.
  PMID: 2532196 [PubMed - indexed for MEDLINE]
• Effects of exercise of varying duration on sarcoplasmic reticulum function.
  Byrd SK, Bode AK, Klug GA.
  J Appl Physiol. 1989 Mar;66(3):1383-9.
  PMID: 2523376 [PubMed - indexed for MEDLINE]
• Modification of the functional capacity of sarcoplasmic reticulum membranes in patients suffering from chronic fatigue syndrome.
  Fulle S, Belia S, Vecchiet J, Morabito C, Vecchiet L, Fanò G.
  Neuromuscul Disord. 2003 Aug;13(6):479-84.
  PMID: 12899875 [PubMed - indexed for MEDLINE]
• Ca2+-ATPase deficiency in a patient with an exertional muscle pain syndrome.
  Taylor DJ, Brosnan MJ, Arnold DL, Bore PJ, Styles P, Walton J, Radda GK.
  J Neurol Neurosurg Psychiatry. 1988 Nov;51(11):1425-33.
  PMID: 2976810 [PubMed - indexed for MEDLINE] Free PMC Article
  Related citations
• [Damage to the Ca2+-transport system of cardiac sarcoplasmic reticulum during emotion-pain stress].
  Meerson FZ, Arkhipenko IuV, Rozhitskaia II, Kagan VE.
  Biull Eksp Biol Med. 1981 Apr;91(4):405-6. Russian.
  PMID: 6114758 [PubMed - indexed for MEDLINE]
• Temporal pattern of plasma membrane calcium ATPase 2 expression in the spinal cord correlates with the course of clinical symptoms in two rodent models of autoimmune encephalomyelitis.
  Nicot A, Kurnellas M, Elkabes S.
  Eur J Neurosci. 2005 May;21(10):2660-70.
  PMID: 15926914 [PubMed - indexed for MEDLINE] Free PMC Article
• Plasma membrane calcium ATPase deficiency causes neuronal pathology in the spinal cord: a potential mechanism for neurodegeneration in multiple sclerosis and spinal cord injury.
  Kurnellas MP, Nicot A, Shull GE, Elkabes S.
  FASEB J. 2005 Feb;19(2):298-300. Epub 2004 Dec 2.
  PMID: 15576480 [PubMed - indexed for MEDLINE] Free PMC Article
• Plasma membrane calcium ATPase expression in the rat spinal cord.
  Tachibana T, Ogura H, Tokunaga A, Dai Y, Yamanaka H, Seino D, Noguchi K.
  Brain Res Mol Brain Res. 2004 Nov 24;131(1-2):26-32.
  PMID: 15530649 [PubMed - indexed for MEDLINE]
• Regulation of gene expression in experimental autoimmune encephalomyelitis indicates early neuronal dysfunction.
  Nicot A, Ratnakar PV, Ron Y, Chen CC, Elkabes S.
  Brain. 2003 Feb;126(Pt 2):398-412.
  PMID: 12538406 [PubMed - indexed for MEDLINE] Free Article
• Analysis of gene expression following spinal cord injury in rat using complementary DNA microarray.
  Tachibana T, Noguchi K, Ruda MA.
  Neurosci Lett. 2002 Jul 19;327(2):133-7.
  PMID: 12098653 [PubMed - indexed for MEDLINE]

• [The relationship between alteration of mitochondrial enzyme activities and mitochondrial function after cervical cord injury].
  Xiao J, Fu Q, Hou T, Li Y, Zhao D.
  Zhongguo Ying Yong Sheng Li Xue Za Zhi. 1997 Nov;13(4):326-8. Chinese.
  PMID: 10322962 [PubMed - indexed for MEDLINE]
• The role of voltage-gated Ca2+ channels in anoxic injury of spinal cord white matter.
  Imaizumi T, Kocsis JD, Waxman SG.
  Brain Res. 1999 Jan 30;817(1-2):84-92.
  PMID: 9889329 [PubMed - indexed for MEDLINE]
• Changes in the distribution of a calcium-dependent ATPase during demyelination and remyelination in the central nervous system.
  Felts PA, Smith KJ.
  J Neurocytol. 1996 Mar;25(3):171-80.
  PMID: 8737170 [PubMed - indexed for MEDLINE]
• [ATPase activity of the guinea pig central nervous system tissue with experimental allergic encephalomyelitis].
  Metal'nikova NP, Terlets'ka IaT, Belik IaV, Chepurko VN.
  Ukr Biokhim Zh. 1977 Jul-Aug;49(4):103-7. Ukrainian.
  PMID: 143099 [PubMed - indexed for MEDLINE]
• [Considerations about study on mechanisms of acupuncture underlying efficacy-enhancement and toxicity-attenuation of digitalis drugs for heart failure].
  Ma SH, Gao JH, Wang YM, Zhang M, Ma YY, Hu JJ, Fu WX, Cui HF, Yu XC.
  Zhen Ci Yan Jiu. 2011 Jun;36(3):225-9. Chinese.
  PMID: 21793390 [PubMed - indexed for MEDLINE]
• [Effects of manual acupuncture and electroacupuncture on Ca2+ content and Ca2+ -ATPase Activity in sarcoplasmic reticulum of skeletal muscle cells in rats during acute swimming exercise].
  Gao M, Yang HY, Le K, Liu TY, Gu XJ.
  Zhen Ci Yan Jiu. 2008 Feb;33(1):13-6. Chinese.
  PMID: 18386638 [PubMed - indexed for MEDLINE]
• [Effects of acupuncture at the points of the Pericardium Meridian on the activity of myocardial Ca2+-ATPase and gene expression in the rat of myocardial ischemia and reperfusion injury].
  Tian YF, Wang R, Li LY, Wang J, Jin CN, Hao CY.
  Zhongguo Zhen Jiu. 2007 Mar;27(3):205-8. Chinese.
  PMID: 17432649 [PubMed - indexed for MEDLINE]
• [Effects of manual acupuncture and electroacupuncture on mitochondria of skeletal muscle cells in rats of acute swimming exercise].
  Gao M, Yang HY, Liu TY, Kuai L.
  Zhongguo Zhen Jiu. 2005 Jun;25(6):421-4. Chinese.
• Decreased sodium-potassium and calcium adenosine triphosphatase activity in asthma: modulation by inhaled and oral corticosteroids.
  Chhabra SK, Khanduja A, Jain D.
  Indian J Chest Dis Allied Sci. 1999 Jan-Mar;41(1):15-26.
  PMID: 10639760 [PubMed - indexed for MEDLINE]
• Increased intracellular calcium and decreased activities of leucocyte Na+,K+-ATPase and Ca2+-ATPase in asthma.
  Chhabra SK, Khanduja A, Jain D.
  Clin Sci (Lond). 1999 Nov;97(5):595-601.
  PMID: 10545310 [PubMed - indexed for MEDLINE] Free Article
• Evidence for an increased intracellular free calcium concentration in platelets of bronchial asthma patients.
  Kuroda S, Ishikawa K, Hanamitsu H, Komori M, Komiya K, Ichikawa Y, Maejima K, Hasegawa K, Ninomiya R, Kuroda M, et al.
  Intern Med. 1995 Aug;34(8):722-7.
  PMID: 8563109 [PubMed - indexed for MEDLINE] Free Article
• Effects of three different Ca(2+)-ATPase inhibitors on Ca2+ response and leukotriene release in RBL-2H3 cells.
  Akasaka R, Teshima R, Ikebuchi H, Sawada J.
  Inflamm Res. 1996 Dec;45(12):583-9.
  PMID: 8988402 [PubMed - indexed for MEDLINE]
• Effects of hydroquinone-type and phenolic antioxidants on calcium signals and degranulation of RBL-2H3 cells.
  Akasaka R, Teshima R, Kitajima S, Momma J, Inoue T, Kurokawa Y, Ikebuchi H, Sawada J.
  Biochem Pharmacol. 1996 Jun 14;51(11):1513-9.
  PMID: 8630092 [PubMed - indexed for MEDLINE]
• A screening method for antigen-specific IgE using mast cells based on intracellular calcium signaling.
  Aketani S, Teshima R, Sawada J, Umezawa Y.
  Anal Chem. 2000 Jun 1;72(11):2653-8.
  PMID: 10857650 [PubMed - indexed for MEDLINE]
• Effect of Ca(2+) ATPase inhibitors on MCP-1 release from bone marrow-derived mast cells and the involvement of p38 MAP kinase activation.
  Teshima R, Onose J, Okunuki H, Sawada J.
  Int Arch Allergy Immunol. 2000 Jan;121(1):34-43.
  PMID: 10686507 [PubMed - indexed for MEDLINE]
• Effects of 2,5-di(tert-butyl)-1,4-hydroquinone on intracellular free Ca2+ levels and histamine secretion in RBL-2H3 cells.
  Kitajima S, Momma J, Tsuda M, Kurokawa Y, Teshima R, Sawada J.
  Inflamm Res. 1995 Aug;44(8):335-9.
  PMID: 8581520 [PubMed - indexed for MEDLINE]

• Enhancement of allergic responses in vivo and in vitro by butylated hydroxytoluene.
  Yamaki K, Taneda S, Yanagisawa R, Inoue K, Takano H, Yoshino S.
  Toxicol Appl Pharmacol. 2007 Sep 1;223(2):164-72. Epub 2007 May 24
• Methyl jasmonate-induced stimulation of sarcoplasmic reticulum Ca(2+)-ATPase affects contractile responses in rat slow-twitch skeletal muscle.
  Joumaa WH, Bouhlel A, Même W, Léoty C.
  J Pharmacol Exp Ther. 2002 Feb;300(2):638-46.
  PMID: 11805227 [PubMed - indexed for MEDLINE] Free Article
  Related citations Remove from clipboard
• Mechanism of stimulation of the calcium adenosinetriphosphatase by jasmone.
  Starling AP, Hughes G, East JM, Lee AG.
  Biochemistry. 1994 Mar 15;33(10):3023-31.
  PMID: 8130215 [PubMed - indexed for MEDLINE]
  Related citations Remove from clipboard
• Comparison of the effects of phospholamban and jasmone on the calcium pump of cardiac sarcoplasmic reticulum. Evidence for modulation by phospholamban of both Ca2+ affinity and Vmax (Ca) of calcium transport.
  Antipenko AY, Spielman AI, Kirchberger MA.
  J Biol Chem. 1997 Jan 31;272(5):2852-60.
  PMID: 9006928 [PubMed - indexed for MEDLINE] Free Article
• Antiplatelet activity of epigallocatechin gallate is mediated by the inhibition of PLCgamma2 phosphorylation, elevation of PGD2 production, and maintaining calcium-ATPase activity.
  Jin YR, Im JH, Park ES, Cho MR, Han XH, Lee JJ, Lim Y, Kim TJ, Yun YP.
  J Cardiovasc Pharmacol. 2008 Jan;51(1):45-54.
  PMID: 18209568 [PubMed - indexed for MEDLINE]
  Related citations Remove from clipboard
• Green tea impedes dyslipidemia, lipid peroxidation, protein glycation and ameliorates Ca2+ -ATPase and Na+/K+ -ATPase activity in the heart of streptozotocin-diabetic rats.
  Babu PV, Sabitha KE, Shyamaladevi CS.
  Chem Biol Interact. 2006 Aug 25;162(2):157-64. Epub 2006 Jun 10.
  PMID: 16846594 [PubMed - indexed for MEDLINE]
• Modification of biochemical parameters of gentamicin nephrotoxicity by coenzyme Q10 and green tea in rats.
  Upaganlawar A, Farswan M, Rathod S, Balaraman R.
  Indian J Exp Biol. 2006 May;44(5):416-8.
  PMID: 16708897 [PubMed - indexed for MEDLINE]
• Interactions of 6-gingerol and ellagic acid with the cardiac sarcoplasmic reticulum Ca2+-ATPase.
  Antipenko AY, Spielman AI, Kirchberger MA.
  J Pharmacol Exp Ther. 1999 Jul;290(1):227-34.
  PMID: 10381780 [PubMed - indexed for MEDLINE] Free Article
• Stimulation of sarcoplasmic reticulum Ca(2+)-ATPase by gingerol analogues.
  Ohizumi Y, Sasaki S, Shibusawa K, Ishikawa K, Ikemoto F.
  Biol Pharm Bull. 1996 Oct;19(10):1377-9.
  PMID: 8913517 [PubMed - indexed for MEDLINE]
• Gingerol, a novel cardiotonic agent, activates the Ca2+-pumping ATPase in skeletal and cardiac sarcoplasmic reticulum.
  Kobayashi M, Shoji N, Ohizumi Y.
  Biochim Biophys Acta. 1987 Sep 18;903(1):96-102.
  PMID: 2443170 [PubMed - indexed for MEDLINE]
  Related citations
• Astragalosides rescue both cardiac function and sarcoplasmic reticulum Ca²⁺ transport in rats with chronic heart failure.
  Wang Y, Ji Y, Xing Y, Li X, Gao X.
  Phytother Res. 2012 Feb;26(2):231-8. doi: 10.1002/ptr.3492. Epub 2011 Jun 7.
  PMID: 21656599 [PubMed - indexed for MEDLINE]
  Related citations Remove from clipboard
• Astragalus Improved Cardiac Function of Adriamycin-Injured Rat Hearts by Upregulation of SERCA2a Expression.
  Su D, Li HY, Yan HR, Liu PF, Zhang L, Cheng JH.
  Am J Chin Med. 2009;37(3):519-29.
  PMID: 19606512 [PubMed - indexed for MEDLINE]
  Related citations Remove from clipboard
• Astragaloside IV improved intracellular calcium handling in hypoxia-reoxygenated cardiomyocytes via the sarcoplasmic reticulum Ca-ATPase.
  Xu XL, Chen XJ, Ji H, Li P, Bian YY, Yang D, Xu JD, Bian ZP, Zhang JN.
  Pharmacology. 2008;81(4):325-32. Epub 2008 Mar 18.
  PMID: 18349554 [PubMed - indexed for MEDLINE]