Calcium Supplements Increase Heart Attack Risk by 86%
New research published in the journal Heart has confirmed the findings of two controversial studies on calcium supplementation and heart attack risk published in the British Medical Journal last year, and which found a 24-27% increased risk of heart attack for those who took 500 mg of elemental calcium a day.[1] [2]
The results of this newest review, involving 24,000 people between the ages of 35 and 64, were even more alarming. Those participants who took a regular calcium supplement increased their risk of having a heart attack by 86% versus those who took no calcium supplements at all.
Why Do We Obsessively Consume Rock, Bone And Shell Calcium?
People really should not be so surprised at the idea that calcium supplementation may be toxic to cardiovascular health. After all, many subject themselves to coronary and cardiac calcium scans in order to ascertain their risk of cardiovascular events and/or cardiac mortality. This is because we know that calcium of the wrong kind in the wrong place can result in serious adverse health effects. There are, in fact, quite a few in the field of nutrition who have long warned against supplementation with elemental calcium; which is to say, calcium from limestone, oyster shell, egg shell and bone meal (hydroxylapatite). There are also those who have not needed to be "experts," because they exercised common sense when it came to not eating rocks or shells.
The seemingly universal popularity of taking elemental calcium supplements results from the promotional efforts of conventional health "experts" and organizations like the National Osteoporosis Foundation (whose corporate sponsors include the calcium manufacturers Oscal and Citrical). Also, the World Health Organization created a radically new definition of "normal" bone density in 1994 when it took the 25-year old young adult standard (which is peak bone mass in a women's life cycle), also known as the "T-score," and applied it to all women, irrespective of their age.
This resulted in redefining the normal and gradual loss of bone mineral density that comes with aging as a disease, essentially medicalizing a non-condition. It also resulted in millions of women being coerced into taking unnecessary (and dangerous) "bone-building" drugs and inorganic calcium supplements to drive bone mineral density higher, by any means necessary. Suddenly, healthy women were being told they had a disease called "osteopenia" or "osteoporosis," even while their bone mineral density was normal for their age, gender and ethnicity (which would have been clear as day, had the age-mediated "Z-score" been used). Moreover, the #1 and #2 cause of death in women are heart disease and cancer, respectively, with heart attack and breast cancer being the primary causes of morbidity and mortality.
When you consider that the risk of death as a side effect of fracture associated with low bone mineral density is infinitesimal relative to that of dying from calcium-induced heart attack, and/or high bone mineral density associated malignant breast cancer (300% higher risk for those in the top quarter percentile of BMD), the justification for promoting osteopenia/osteoporosis prevention and/or treatment in women's health above far more serious and likely health threats completely falls apart. In fact, it appears that this myopic fixation may be significantly contributing to their premature death.
Turned To Stone: When Calcium Goes To The Wrong Place
The reality is that the habit of consuming inorganic, elemental calcium simply does not make sense. After all, have you ever experienced visceral disgust after accidentally consuming eggshell? If you have, you know your body is "hard-wired" to reject low-quality calcium sources (stones and bones as it were), in favor of getting calcium from food.
Inorganic or "elemental" calcium, when not bound to the natural co-factors, e.g. amino acids, lipids and glyconutrients, found in "food" (which is to say other living beings, e.g. plants and animals), no longer has the intelligent delivery system that enables your body to utilize it in a biologically appropriate manner. Lacking this "delivery system," the calcium may end up going to places you do not want (ectopic calcification), or go to places you do want (e.g. the bones), but in excessive amounts, stimulating unnaturally accelerated cell-division (osteoblasts), resulting in higher bone turnover rates later in life (this is explained in the article below).
Or, the body attempts to disburden itself of this inappropriate calcium and dumps it into the bowel (constipation), or pushes it through the kidneys (stones). Worse, high levels of calcium can accumulate in the blood (hypercalcemia), which can contribute to destabilizing the atherosclerotic plaque through the formation of a brittle calcium cap on the atheroma, can contribute to thrombosis (clot) formation, hypertension (that's why we use calcium channel blockers to lower blood pressure), and perhaps causing arrhythmias/fibrillation and or heart muscle cramping, or coronary artery spasm (a rather common, though rarely recognized trigger of 'heart attack').
The breasts too are uniquely susceptible to ectopic calcification, which is why we use the same x-rays to ascertain bone density that we do to discern pathological microcalcifications in the breast, i.e. x-ray mammography. Due to the fact that the hydroxylapatitate crystals found in malignant breast tissue may act as a cellular 'signaling molecule' or mitogen (inducing cell proliferation), it is possible that certain breast calcifications may be a cause, and not just an effect, of the tumorous lesions ("breast cancer") found there. This may also help to explain why women with the highest bone density (often obtained through massive, lifelong calcium supplementation) have up to 300% higher incidence of malignant breast cancer.
"Brain gravel" is also an increasingly prevalent phenomenon, where autopsied patients have been found to have pebble-size calcium deposits distributed throughout their brains, including the pineal gland ('the seat of the soul'). The wide range of existing calcium-associated pathologies, and their increasing prevalence in calcium-fixated cultures, demand further investigation and explanation. One aspect of this, no doubt, is our obsessive cultural fixation on mega-dose calcium supplementation for non-existing "conditions" associated with bone mineral density that is normal-for-our-age, but not for our doctors and the "experts" who guide them with industry-friendly misinformation.
I believe this new research puts the nail in the coffin of any remaining doubt that we should stay as far away from inorganic calcium supplements as possible, as well as the empirically and intellectually bankrupt disease models being used to coerce women into taking them in the first place.
Stoned To Death: Calcium Supplements Proven To Kill Again http://www.greenmedinfo.com/blog/turned-stone-calcium-pills-proven-once-again-kill
椎骨密度与冠状动脉钙化有关，是终末期肾脏疾病患者预后不良的独立预测因子
1瑞典斯德哥尔摩卡罗林斯卡研究所干预与技术临床科学系肾脏医学和Baxter Novum部门；浙江大学附属第一医院医学院肾脏病中心，杭州
2瑞典斯德哥尔摩卡罗林斯卡研究所干预与技术临床科学系肾脏医学和Baxter Novum部门。
3瑞典斯德哥尔摩卡罗林斯卡研究所临床科学，干预与技术系医学影像与技术部门；瑞典胡丁德卡罗林斯卡大学医院放射科。
4瑞典斯德哥尔摩Karolinska研究所临床科学，干预和技术系移植手术科。
5瑞典斯德哥尔摩Karolinska研究所临床科学，干预和技术系肾脏医学和Baxter Novum部门。电子地址：peter.stenvinkel@ki.se。
目的：慢性肾脏疾病-矿物质骨疾病（CKD-MBD）是终末期肾脏疾病（ESRD）的主要并发症。骨矿物质密度（BMD）降低与血管钙化有关。在这里，我们研究了通过心脏计算机断层扫描（CT）量化的椎骨密度（VBD）和冠状动脉钙化（CAC）之间的关联，以及通过双能X线骨密度仪（DXA）量化的BMD及其与死亡率的关系。
方法：对231例ESRD患者（中位年龄56岁，男性63％）进行了分析，包括事件透析患者，普遍的腹膜透析患者和活体供肾移植的接受者，VBD（Hounsfield单位，HUs）和CAC评分（Agatston单位，AUs）。通过心脏CT检查，在143例患者中，通过全身DXA测量BMD。还分析了可能与CKD-MBD相关的代谢和炎症生物标志物。
结果：VBD三分位数较低的患者年龄较大，患有心血管疾病（CVD）的频率更高，HbA1c（非糖尿病），白介素6和CAC评分较高。在调整了年龄，性别，糖尿病，CVD，炎症和队列后，低VBD与较高的CAC评分（> 100 AUs）独立相关。在Cox比例风险分析中，在调整了年龄，性别，糖尿病，CVD，炎症和主观整体评估（SGA）之后，低VBD与全因死亡率独立相关。预测的均方根误差（RMSE）显示了DXA评估的VBD和BMD之间的良好关联程度。在接受者－操作者特征曲线（ROC）分析中，与DXA评估的BMD相比，较低的VBD与较高的CAC评分和全因死亡率更紧密相关。
结论：虽然DXA和CT对BMD的评估显示出良好的一致性，但高CAC和死亡率，低VBD的关联性强于DXA基于低BMD的关联。低VBD与高CAC评分和增加的死亡风险之间有很强的独立联系，表明VBD可能是ESRD患者的重要预后指标。Vertebral bone density associates with coronary artery calcification and is an independent predictor of poor outcome in end-stage renal disease patients - PubMed
https://pubmed.ncbi.nlm.nih.gov/27519971/
肾脏疾病中血管钙化的机制
泰国曼谷玛希隆大学拉马西波迪医院医学院内科肾病科
慢性肾脏疾病中血管钙化的患病率和严重性增加是血管床，矿物质代谢物和其他尿毒症因素变化之间复杂相互作用的结果。 血管钙化可发生在动脉壁的内膜和中层。 在允许的条件下，血管平滑肌细胞（VSMC）可以转化为成骨细胞样表型。 从转化的VSMC释放的膜结合的囊泡和从垂死的VSMC衍生的凋亡小体充当钙晶体形成的成核结构。 内源性钙化抑制剂的质量和数量的变化也产生了增强钙化的环境。Mechanisms of Vascular Calcification in Kidney Disease - ScienceDirect
https://www.sciencedirect.com/science/article/abs/pii/S1548559519301545
ERK1/2 inhibition reduces vascular calcification by activating miR-126-3p-DKK1/LRP6 pathway
Peng Zeng1*, Jie Yang1*, Lipei Liu1, Xiaoxiao Yang2, Zhi Yao3, Chuanrui Ma4, Haibo Zhu5, Jiamin Su2, Qian Zhao2, Ke Feng1, Shu Yang1, Yan Zhu6, Xiaoju Li1, Wenguang Wang7, Yajun Duan2, Jihong Han1,2 Corresponding address, Yuanli Chen2 Corresponding address
1. College of Life Sciences, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of Ministry of Education, Nankai University, Tianjin, China.
2. Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes, Hefei University of Technology, Hefei, China.
3. Tianjin Medical University, Tianjin, China.
4. First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.
5. Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
6. Tianjin University of Traditional Chinese Medicine, Tianjin, China.
7. Tianjin Chest Hospital, Tianjin, China.
https://www.thno.org/v11p1129.htm
Vitamin C attenuates ERK signalling to inhibit the ...
onlinelibrary.wiley.com/doi/10.1111/j.1600-0625.2010.01070.x/full
Aug 01, 2010 · Ulrich-Merzenich et al. also demonstrated that physiological concentrations of vitamin C promote DNA synthesis and proliferation in endothelial cells via targeting ERK1/2 and ERK5 without activating the stress-related MAPK p38 or c-Jun . In contrast to what these previous studies have shown, we demonstrate that vitamin C enhances collagen production in HDF by inhibiting phosphorylation of …
ERK1/2 inhibition reduces vascular calcification by activating miR-126-3p-DKK1/LRP6 pathway
Peng Zeng1*, Jie Yang1*, Lipei Liu1, Xiaoxiao Yang2, Zhi Yao3, Chuanrui Ma4, Haibo Zhu5, Jiamin Su2, Qian Zhao2, Ke Feng1, Shu Yang1, Yan Zhu6, Xiaoju Li1, Wenguang Wang7, Yajun Duan2, Jihong Han1,2 Corresponding address, Yuanli Chen2 Corresponding address
1. College of Life Sciences, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of Ministry of Education, Nankai University, Tianjin, China.
2. Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes, Hefei University of Technology, Hefei, China.
3. Tianjin Medical University, Tianjin, China.
4. First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.
5. Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
6. Tianjin University of Traditional Chinese Medicine, Tianjin, China.
7. Tianjin Chest Hospital, Tianjin, China.
https://www.thno.org/v11p1129.htm
Vitamin C attenuates ERK signalling to inhibit the regulation of collagen production by LL‐37 in human dermal fibroblasts
onlinelibrary.wiley.com/doi/10.1111/j.1600-0625.2010.01070.x/full
Aug 01, 2010 ·
Abstract: Vitamin C is used as an anti‐ageing agent because of its collagen enhancing effects. The precise cellular signalling mechanism of vitamin C is not well known. Here, we investigate the profibrotic mechanism of vitamin C against LL‐37. Antimicrobial peptide LL‐37 decreases collagen expression at mRNA and protein levels in human dermal fibroblasts (HDFs). The ability of LL‐37 to inhibit collagen expression is dependent on phosphorylation of extracellular signal‐regulated kinase (ERK). HDFs and human keloid fibroblasts were treated with vitamin C followed by 2 h of LL‐37 treatment. Collagen mRNA expression and total soluble collagen production inhibited by LL‐37 was enhanced by treatment with 0.5 mm vitamin C. Vitamin C also decreased intracellular reactive oxygen intermediates (ROI) levels that were increased by LL‐37. Furthermore, the phosphorylation of ERK was analysed by Western blot following treatment with vitamin C and LL‐37. Vitamin C turned off phosphorylation of ERK that was induced by LL‐37. Ets‐1 transcriptional factor, which is involved in the regulation of collagen expression by LL‐37, was also inhibited by vitamin C. This study shows that vitamin C enhances collagen production by inhibiting the ERK pathway induced by LL‐37.ERK1 / 2抑制通过激活miR-126-3p-DKK1 / LRP6途径减少血管钙化
彭增1 *，杨洁1 *，刘立佩1，杨晓晓2，智瑶3，马传瑞4，海博珠5，贾敏苏2，钱昭2，柯峰1，舒扬1，严竹6，李小菊1，文光望7，段亚军2，季洪汉1， 2通讯地址陈远丽2通讯地址
1.南开大学生命科学学院，药物化学生物学国家重点实验室，生物活性材料教育部重点实验室，天津
2.合肥工业大学安徽高等学校代谢与主要疾病代谢与调控重点实验室，合肥
3.天津医科大学，中国天津。
4.天津中医药大学第一教学医院，天津
5.中国医学科学院北京协和医学院，北京。
6.天津中医药大学，天津
7.天津市胸科医院，中国天津。
https://www.thno.org/v11p1129.htm
维生素C减弱ERK信号转导以抑制人真皮成纤维细胞中LL-37对胶原蛋白产生的调节
onlinelibrary.wiley.com/doi/10.1111/j.1600-0625.2010.01070.x/完整
2010年8月1日·
摘要：维生素C由于具有增强胶原蛋白的作用而被用作抗衰老剂。维生素C的精确细胞信号转导机制尚不清楚。在这里，我们研究了维生素C对LL-37的促纤维化机制。抗菌肽LL-37降低人皮肤成纤维细胞（HDF）中mRNA和蛋白水平的胶原蛋白表达。 LL-37抑制胶原蛋白表达的能力取决于细胞外信号调节激酶（ERK）的磷酸化。 HDF和人瘢痕loid成纤维细胞先用维生素C处理，再用2小时的LL-37处理。用0.5μmm的维生素C处理可增强LL-37抑制的胶原mRNA表达和总可溶性胶原产生。维生素C还降低了细胞内活性氧中间体（ROI）的水平，而LL-37增加了该水平。此外，维生素C和LL-37处理后，通过蛋白质印迹分析了ERK的磷酸化。维生素C关闭了LL-37诱导的ERK磷酸化。 Ets-1转录因子也参与了LL-37调节胶原蛋白的表达，维生素C也被抑制。这项研究表明，维生素C通过抑制LL-37诱导的ERK途径来增强胶原蛋白的产生。
Arterioscler Thromb Vasc Biol
. 2010 Sep;
Chondrocyte rather than osteoblast conversion of vascular cells underlies medial calcification in uremic rats
Objective: To investigate cell biological changes in calcified aortas of rats that experienced chronic renal failure.
Methods and results: Vascular smooth muscle cells have the potential to transdifferentiate to either chondrocytes or osteoblasts, depending on the molecular pathways that are stimulated. Uremia-related medial calcification was induced by feeding rats an adenine low-protein diet for 4 weeks. Aortic calcification was evaluated biochemically and histochemically and with in vivo micro-computed tomographic scanning. Immunohistochemistry and RT-PCR were applied to analyze the time-dependent aortic expression of molecules involved in the segregation between the chondrocyte versus osteoblast differentiation pathway. After 4 weeks, 85% of the uremic rats had developed distinct aortic medial calcification, which increased to severely calcified lesions during further follow-up. The calcification process was accompanied by a significant time-dependent increase in the expression of the chondrocyte-specific markers sex determining region Y-box 9 (sox9), collagen II, and aggrecan and a nonsignificant trend toward enhanced core binding factor alpha 1 (cbfa1), and collagen I. The expression of the osteoblast marker osterix and both lipoprotein receptor-related protein 6 and beta-catenin, molecules of the wingless-type MMTV integration site family member (Wnt)/beta-catenin pathway induced during osteoblast differentiation, was suppressed.
Conclusions: In the aorta of uremic rats, medial smooth muscle cells acquire a chondrocyte rather than osteoblast phenotype during the calcification process.动脉血栓栓塞血管2010 Sep; 30
尿毒症大鼠的内侧钙化是软骨细胞而非成骨细胞转化为血管细胞的基础
目的：研究慢性肾功能衰竭大鼠钙化主动脉的细胞生物学变化。
方法和结果：血管平滑肌细胞可能会分化为软骨细胞或成骨细胞，具体取决于受刺激的分子途径。通过给大鼠饲喂腺嘌呤低蛋白饮食4周来诱导与尿毒症相关的内侧钙化。通过生物化学和组织化学以及体内微计算机断层扫描对主动脉钙化进行评估。应用免疫组织化学和RT-PCR技术分析了软骨细胞与成骨细胞分化途径之间的分离所涉及的分子的时间依赖性主动脉表达。 4周后，85％的尿毒症大鼠已形成明显的主动脉内侧钙化，在进一步的随访过程中增加为严重钙化病变。钙化过程伴随着软骨细胞特异性标志物性别决定区Y-box 9（sox9），胶原蛋白II和聚集蛋白聚糖表达的显著时间依赖性增加，且核心结合因子α1（cbfa1）的增加趋势不明显。 ）和胶原I。成骨细胞分化过程中诱导的无翼型MMTV整合位点家族成员（Wnt）/β-catenin途径的分子，成骨细胞标志物osterix以及脂蛋白受体相关蛋白6和β-catenin的表达，被压制了。
结论：在尿毒症大鼠的主动脉中，钙化过程中，内侧平滑肌细胞获得软骨细胞而不是成骨细胞表型。
Chondrocyte rather than osteoblast conversion of vascular cells underlies medial calcification in uremic rats - PubMed
https://pubmed.ncbi.nlm.nih.gov/20522801/
Dev Cell. 2017 Jun 5
Endothelial-to-Osteoblast Conversion Generates Osteoblastic Metastasis of Prostate Cancer
Abstract
Prostate cancer (PCa) bone metastasis is frequently associated with bone-forming lesions, but the source of the osteoblastic lesions remains unclear. We show that the tumor-induced bone derives partly from tumor-associated endothelial cells that have undergone endothelial-to-osteoblast (EC-to-OSB) conversion. The tumor-associated osteoblasts in PCa bone metastasis specimens and patient-derived xenografts (PDXs) were found to co-express endothelial marker Tie-2. BMP4, identified in PDX-conditioned medium, promoted EC-to-OSB conversion of 2H11 endothelial cells. BMP4 overexpression in non-osteogenic C4-2b PCa cells led to ectopic bone formation under subcutaneous implantation. Tumor-induced bone was reduced in trigenic mice (Tie2cre/Osxf/f/SCID) with endothelial-specific deletion of osteoblast cell-fate determinant OSX compared with bigenic mice (Osxf/f/SCID). Thus, tumor-induced EC-to-OSB conversion is one mechanism that leads to osteoblastic bone metastasis of PCa.
Keywords: bone metastasis; endothelial-to-osteoblast conversion; osteoblast; paracrine factors; prostate cancer; proteomics.Dev Cell。 2017年6月5日
内皮细胞向成骨细胞的转化产生前列腺癌的成骨细胞转移
抽象
前列腺癌（PCa）骨转移通常与骨形成病变有关，但成骨病变的来源仍不清楚。我们表明，肿瘤诱导的骨部分来源于肿瘤相关的内皮细胞，这些细胞已经经历了内皮向成骨细胞（EC到OSB）的转化。发现PCa骨转移标本中的肿瘤相关成骨细胞和患者衍生的异种移植物（PDXs）共表达内皮标记Tie-2。在PDX条件培养基中鉴定出的BMP4促进了2H11内皮细胞从EC到OSB的转化。非成骨C4-2b PCa细胞中的BMP4过表达导致皮下植入后异位骨的形成。与双基因小鼠（Osxf / f / SCID）相比，三基因小鼠（Tie2cre / Osxf / f / SCID）的内皮细胞特异性决定因素OSX的内皮特异性缺失减少了肿瘤诱导的骨骼。因此，肿瘤诱导的EC到OSB的转化是导致PCa成骨骨转移的一种机制。
关键词：骨转移；内皮到成骨细胞的转化；成骨细胞旁分泌因子前列腺癌;蛋白质组学。Endothelial-to-Osteoblast Conversion Generates Osteoblastic Metastasis of Prostate Cancer - PubMed
https://pubmed.ncbi.nlm.nih.gov/28586644/
Mechanism of vascular calcification in Kidney Disease
The increase in prevalence and severity of vascular calcification in chronic kidney disease is a result of complex interactions between changes in the vascular bed, mineral metabolites, and other uremic factors. Vascular calcification can occur in the intima and the media of arterial wall. Under permissive conditions, vascular smooth muscle cells (VSMCs) can transform to osteoblast-like phenotype. The membrane-bound vesicles released from transformed VSMCs and the apoptotic bodies derived from dying VSMCs serve as nucleating structures for calcium crystal formation. Alterations in the quality and the quantity of endogenous calcification inhibitors also give rise to an environment that potentiates calcification.
Mechanisms of Vascular Calcification in Kidney Disease - Advances in Chronic Kidney Disease
https://www.ackdjournal.org/article/S1548-5595(19)30154-5/fulltext
Metabolic Acidosis | National Kidney Foundation
https://www.kidney.org/atoz/content/metabolic-acidosis
May 23, 2016 · The buildup of acid in the body due to kidney disease or kidney failure is called metabolic acidosis. When your body fluids contain too much acid, it means that your body is either not getting rid of enough acid, is making too much acid, or cannot balance the acid in your body. What causes metabolic acidosis? Healthy kidneys have many jobs.
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