Statins in the Cause and Prevention of Cancer: Confounding by Indication and Mediation by Rhabdomyolysis and Phosphate Toxicity.

Statins are drugs used in cardiovascular pharmacotherapy to decrease hypercholesterolemia and lower the risk of atherosclerosis. Statins also increase the risk of rhabdomyolysis, which is often minimized in comparison with large relative risk reductions of cardiovascular disease reported in clinical trials. By contrast, absolute risk reductions of cardiovascular disease are often clinically insignificant and unreported in statin clinical trials.

Spontaneous Tumor Regression and Reversion: Insights and Associations with Reduced Dietary Phosphate.

Tumors that spontaneously shrink from unknown causes in tumor regression, and that return to normal cells in tumor reversion, are phenomena with the potential to contribute new knowledge and novel therapies for cancer patient survival. Tumorigenesis is associated with dysregulated phosphate metabolism and an increased transport of phosphate into tumor cells, potentially mediated by phosphate overload from excessive dietary phosphate intake, a significant problem in Western societies. This paper proposes that reduced dietary phosphate overload and reregulated phosphate metabolism may reverse an imbalance of kinases and phosphatases in cell signaling and cellular proliferation, thereby activating autophagy in tumor regression and reversion.

Can a Low-Phosphate Diet for Chronic Kidney Disease Treat Cancer? An Interdisciplinary Literature Review.

Cancer therapeutics have a low success rate in clinical trials. An interdisciplinary approach is needed to translate basic, clinical, and remote fields of research knowledge into novel cancer treatments. Recent research has identified high dietary phosphate intake as a risk factor associated with cancer incidence.

Myopia, Sodium Chloride, and Vitreous Fluid Imbalance: A Nutritional Epidemiology Perspective.

Theories of myopia etiology based on near work and lack of outdoor exposure have had inconsistent support and have not prevented the rising prevalence of global myopia. New scientific theories in the cause and prevention of myopia are needed. Myopia prevalence is low in native people consuming traditional diets lacking in sodium chloride, and nutritional epidemiological evidence supports the association of rising myopia prevalence with dietary sodium intake.

Breast Cancer and Bone Mineral Density in a U.S. Cohort of Middle-Aged Women: Associations with Phosphate Toxicity.

Breast cancer is associated with phosphate toxicity, the toxic effect from dysregulated phosphate metabolism that can stimulate tumorigenesis. Phosphate toxicity and dysregulated phosphate metabolism are also associated with bone mineral abnormalities, including excessive bone mineral loss and deposition. Based on shared associations with dysregulated phosphate metabolism and phosphate toxicity, a hypothesis proposed in the present mixed methods-grounded theory study posits that middle-aged women with incidence of breast cancer had a greater magnitude of changes in bone mineral density over time compared with women who remained cancer-free.

High Dietary Phosphorus Is Associated with Increased Breast Cancer Risk in a U.S. Cohort of Middle-Aged Women.

Research has shown that high amounts of dietary phosphorus that are twice the amount of the U.S. dietary reference intake of 700 mg for adults are associated with all-cause mortality, phosphate toxicity, and tumorigenesis.

Salt-Sensitive Hypertension: Mediation by Salt-Induced Hypervolemia and Phosphate-Induced Vascular Calcification.

Preventing hypertension by restricting dietary salt intake, sodium chloride, is well established in public health policy, but a pathophysiological mechanism has yet to explain the controversial clinical finding that some individuals have a greater risk of hypertension from exposure to salt intake, termed salt-sensitive hypertension. The present perspective paper synthesizes interdisciplinary findings from the research literature and offers novel insights proposing that the pathogenesis of salt-sensitive hypertension is mediated by interaction of salt-induced hypervolemia and phosphate-induced vascular calcification. Arterial stiffness and blood pressure increase as calcification in the vascular media layer reduces arterial elasticity, preventing arteries from expanding to accommodate extracellular fluid overload in hypervolemia related to salt intake.

Breast cancer, alcohol, and phosphate toxicity.

Alcohol consumption is associated with an increased risk of breast cancer, even at low alcohol intake levels, but public awareness of the breast cancer risk associated with alcohol intake is low. Furthermore, the causative mechanisms underlying alcohol's association with breast cancer are unknown. The present theoretical paper uses a modified grounded theory method to review the research literature and propose that alcohol's association with breast cancer is mediated by phosphate toxicity, the accumulation of excess inorganic phosphate in body tissue.

Dysregulated phosphate metabolism in autism spectrum disorder: associations and insights for future research.

Studies of autism spectrum disorder (ASD) related to exposure to toxic levels of dietary phosphate are lacking. Phosphate toxicity from dysregulated phosphate metabolism can negatively impact almost every major organ system of the body, including the central nervous system. The present paper used a grounded theory-literature review method to synthesise associations of dysregulated phosphate metabolism with the aetiology of ASD.

Phosphate toxicity and SERCA2a dysfunction in sudden cardiac arrest.

Almost half of the people who die from sudden cardiac arrest have no detectable heart disease. Among children and young adults, the cause of approximately one-third of deaths from sudden cardiac arrest remains unexplained after thorough examination. Sudden cardiac arrest and related sudden cardiac death are attributed to dysfunctional cardiac ion-channels.

Relative risk reduction: Misinformative measure in clinical trials and COVID-19 vaccine efficacy.

Unlabelled: Treatment and vaccine efficacy in clinical trials are often reported in the media and medical journals as the relative risk reduction. The present article explains why the relative risk reduction is a misinformative measure that promotes disinformation when reporting efficacy in clinical research studies such as randomized controlled trials for COVID-19 vaccines. The relative risk reduction is based on the relative risk, a proportional measure or ratio used in epidemiologic studies to estimate the probability of a disease associated with an exposure.

Cancer Cachexia and Dysregulated Phosphate Metabolism: Insights from Mutant p53 and Mutant Klotho Mouse Models.

The present perspective article proposes that cachexia, muscle wasting in cancer, is mediated by dysregulated phosphate metabolism and phosphate toxicity that can damage tissues in most major organ systems. A diet high in phosphorus fed to mice deficient in klotho, a cofactor that regulates phosphate metabolism, accelerates aging, sarcopenia, general organ atrophy, kyphosis, and osteoporosis. Similar effects are seen in phenotypes of mutant p53 mice that overexpress the p53 tumor suppressor gene.

Correction: Brown, R.B. Sodium Chloride, Migraine and Salt Withdrawal: Controversy and Insights. 2021, , 67.

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Biases in COVID-19 Case and Death Definitions: Potential Causes and Consequences.

This paper investigates three controversies involving potential causes and consequences of information bias in case and death definitions during the coronavirus disease (COVID-19) pandemic. First, evidence suggests China's surveillance data were biased and misinterpreted by the World Health Organization (WHO), prompting the WHO to advise nations to copy China's lockdowns. China appeared to use narrow diagnostic definitions that undercounted cases and deaths.

Hypertension, Anxiety and Obstructive Sleep Apnea in Cardiovascular Disease and COVID-19: Mediation by Dietary Salt.

This perspective paper used a grounded theory method to synthesize evidence proposing that sodium toxicity from excessive dietary salt intake is a potential common pathophysiological mechanism that mediates the association of hypertension, obstructive sleep apnea, and anxiety with cardiovascular disease and COVID-19. Increased anxiety in these conditions may be linked to a high-salt diet through stimulation of the sympathetic nervous system, which increases blood pressure while releasing catecholamines, causing a "fight or flight" response. A rostral shift of fluid overload from the lower to the upper body occurs in obstructive sleep apnea associated with COVID-19 and cardiovascular disease, and may be related to sodium and fluid retention triggered by hypertonic dehydration.

Sudden Infant Death Syndrome, Pulmonary Edema, and Sodium Toxicity: A Grounded Theory.

Sudden Infant Death Syndrome (SIDS) occurs unexpectedly in an otherwise healthy infant with no identifiable cause of death following a thorough investigation. A general hypervolemic state has been identified in SIDS, and fluid in the lungs suggests the involvement of pulmonary edema and hypoxia as the cause of death. The present perspective paper reviews pathophysiological, epidemiological, and dietary evidence in SIDS.

Non-Specific Low Back Pain, Dietary Salt Intake, and Posterior Lumbar Subcutaneous Edema.

Low back pain is the world's leading disability, but the etiology of the majority of low back pain is non-specific with no known cause. Moreover, overuse of opioids to treat low back pain is a widespread problem. This paper proposes that non-specific low back pain may be associated with excessive intake of dietary salt, potentially mediated by posterior lumbar subcutaneous edema.

Low dietary sodium potentially mediates COVID-19 prevention associated with whole-food plant-based diets.

Compared with an omnivorous Western diet, plant-based diets containing mostly fruits, vegetables, grains, legumes, nuts and seeds, with restricted amounts of foods of animal origin, are associated with reduced risk and severity of COVID-19. Additionally, inflammatory immune responses and severe acute respiratory symptoms of COVID-19, including pulmonary oedema, shortness of breath, fever and nasopharyngeal infections, are associated with Na toxicity from excessive dietary Na. High dietary Na is also associated with increased risks of diseases and conditions that are co-morbid with COVID-19, including chronic kidney disease, hypertension, stroke, diabetes and obesity.

Parkinson's Disease Etiology: Insights and Associations with Phosphate Toxicity.

The present paper investigated the association of Parkinson's disease etiology with phosphate toxicity, a pathophysiological condition in which dysregulated phosphate metabolism causes excessive inorganic phosphate sequestration in body tissue that damages organ systems. Excessive phosphate is proposed to reduce Complex I function of the mitochondrial electron transport chain in Parkinson's disease and is linked to opening of the mitochondrial permeability transition pore, resulting in increased reactive oxygen species, inflammation, DNA damage, mitochondrial membrane depolarization, and ATP depletion causing cell death. Parkinson's disease is associated with α-synuclein and Lewy body dementia, a secondary tauopathy related to hyperphosphorylation of tau protein, and tauopathy is among several pathophysiological pathways shared between Parkinson's disease and diabetes.

Sodium Chloride, Migraine and Salt Withdrawal: Controversy and Insights.

This paper examines evidence implicating migraine headache as a withdrawal symptom of excessive sodium chloride intake. Emerging research in food addiction posits that food and drug addictions share common features, such as withdrawal symptoms. Salt (sodium chloride) meets the criteria for the diagnosis of substance dependence, including withdrawal in which the substance is used to relieve withdrawal symptoms.

Sodium Toxicity in the Nutritional Epidemiology and Nutritional Immunology of COVID-19.

Dietary factors in the etiology of COVID-19 are understudied. High dietary sodium intake leading to sodium toxicity is associated with comorbid conditions of COVID-19 such as hypertension, kidney disease, stroke, pneumonia, obesity, diabetes, hepatic disease, cardiac arrhythmias, thrombosis, migraine, tinnitus, Bell's palsy, multiple sclerosis, systemic sclerosis, and polycystic ovary syndrome. This article synthesizes evidence from epidemiology, pathophysiology, immunology, and virology literature linking sodium toxicological mechanisms to COVID-19 and SARS-CoV-2 infection.

Outcome Reporting Bias in COVID-19 mRNA Vaccine Clinical Trials.

Relative risk reduction and absolute risk reduction measures in the evaluation of clinical trial data are poorly understood by health professionals and the public. The absence of reported absolute risk reduction in COVID-19 vaccine clinical trials can lead to outcome reporting bias that affects the interpretation of vaccine efficacy. The present article uses clinical epidemiologic tools to critically appraise reports of efficacy in Pfzier/BioNTech and Moderna COVID-19 mRNA vaccine clinical trials.

Stress, inflammation, depression, and dementia associated with phosphate toxicity.

Depression and dementia are predicted to increase within aging global populations. Pathophysiological effects of phosphate toxicity, dysregulated amounts of accumulated phosphorus in body tissue, are under-investigated in association with stress, inflammation, depression, and dementia. A comparative analysis of concepts in cited sources from the research literature was used to synthesize novel themes exploring the disease-oriented neuroscience effects of phosphate toxicity.

Public Health Lessons Learned From Biases in Coronavirus Mortality Overestimation.

In testimony before US Congress on March 11, 2020, members of the House Oversight and Reform Committee were informed that estimated mortality for the novel coronavirus was 10-times higher than for seasonal influenza. Additional evidence, however, suggests the validity of this estimation could benefit from vetting for biases and miscalculations. The main objective of this article is to critically appraise the coronavirus mortality estimation presented to Congress.

Potential interaction of inflammatory hyperemia and hyperphosphatemia in tumorigenesis.

The present article proposes that the association of inflammation with cancer is potentially mediated by the interaction of inflammatory hyperemia and hyperphosphatemia. Hyperemia increases blood flow rate and blood volume, and hyperphosphatemia is caused by elevated serum levels of dysregulated inorganic phosphate. It is hypothesized that the interaction of inflammatory hyperemia and hyperphosphatemia circulates increased amounts of inorganic phosphate to the tumor microenvironment, where increased uptake of inorganic phosphate through sodium-phosphate cotransporters is sequestered in cells.