Cadmium-Induced Zinc Deficiency, Diabetes, and Susceptibility to COVID-19

Perspective on Cadmium-Induced Zinc Deficiency, Diabetes, Its Complications, and Susceptibility to COVID-19

Arturo Riojas, Ph.D., P.E.
[Medical Student At Blue Marble University Medical School]

Key Words: Cadmium, Carcinogen, Cancer, Zinc, Zinc Deficiency, Diabetes Mellitus, Gestational Diabetes, COVID-19, Kidney Disease, Nephropathy, Diseases of the Eye, Atherosclerosis, Cardiovascular Disease, Neuropathy, Alzheimer’s Disease

Introduction

Many of today’s dreaded diseases have a common thread that links them. My hypothesis is that cadmium poisoning is the underlying cause of increased risk for developing type 2 diabetes and a host of other diseases, including COVID-19, resulting from infection by the SARS-CoV-2 virus. More specifically, cadmium itself is a known carcinogen and highly toxic, causing dysfunction of organs where it accumulates, but it also induces zinc deficiency that, in turn, impairs the immune system, sending individuals into a downward spiral with regard to their health. Because cadmium accumulates to different degrees in different locations, driving out zinc in the process, different vulnerabilities exist in different parts of the body for each individual. Zinc within the cell has been shown to be effective at blocking the replication of coronaviruses.(1) When vulnerable zinc-deficient cells are infected, this allows the virus to be replicated and released into the bloodstream where it circulates, seeking out additional vulnerable cells. All this happens before an effective immune system response can be launched. Individuals who are not zinc deficient (e.g., many children and young adults) may exhibit few or no symptoms and are thought to be less susceptible to the virus, but they may still be contagious until their immune systems take charge of eliminating the viral remnants of the disease. Those most vulnerable to COVID-19 are the elderly,(2)  those with underlying health conditions such as diabetes,(3) and those who are immunocompromised.(4) These are the individuals who are most likely to be zinc deficient due to cadmium poisoning.

Focus on Diabetes Mellitus and Its Complications

It is widely accepted that the four major “complications” of type 2 diabetes are atherosclerosis, nephropathy, retinopathy, and neuropathy. The following excerpts suggest that these four complications may be concurrent pathologies due to cadmium that are exacerbated by type 2 diabetes, which tends to be one of the first serious signs of cadmium poisoning, due to its accumulation in the pancreas and the induced zinc deficiency it causes.

Link between diabetes, kidney disease, and cadmium.
• “One of the most serious complications of diabetes is chronic kidney disease, also known as diabetic nephropathy. Diabetic nephropathy is associated with albuminuria, decreased creatinine clearance, altered glomerular morphology and tubular degeneration. Approximately 30-40% of type II diabetic patients will develop diabetic nephropathy, and it is now the most common cause of end stage renal failure in the Western world. . . . Our results suggest a direct effect of Cd on the pancreas and there is evidence that Cd can alter insulin release from pancreatic β-cells. . . . Within the liver, sub-chronic Cd exposure has been shown to increase the activity all four of the enzymes responsible for gluconeogenesis [the metabolic process by which glucose is produced from non-carbohydrate precursors]. . . . Following Cd exposure, adipose, pancreatic, and liver tissues along with the adrenal gland, become injured leading to altered glucose metabolism and/or glucose uptake that ultimately results in increased blood glucose. Elevated blood glucose levels coupled with the direct effects of Cd on renal tissue eventually leads to kidney dysfunction and damage.” (5)

Link between zinc deficiency, diseases of the eye, and diabetes.
• “Zinc has long been recognized as an essential constituent of various tissues. Many clinical conditions and dietary factors reduce the absorption or the biological availability of zinc, and lead to zinc deficiency which produces structural and functional alterations in many organ systems. The highest concentration of this trace element in the human body is measured in the eye, particularly in the pigment-containingcomponents. The deficiency of zinc has a dramatic effect on ocular development especially when it occurs during early prenatal period. Zinc is required for the structure and activity of many ocular metalloenzymes. Although the exact mechanism of its molecular and cellular functions are largely unknown the essentiality of this element in the component of the eye, including the retina, choroid, cornea and lens, is well established; it is also well known that zinc deficiency causes functional impairments in various parts of the eye.” (6)

• “Zinc is important in insulin action and carbohydrate metabolism. Oxidative stress plays an important role in the pathogenesis of diabetes and its complications. Zinc is a structural part of key anti-oxidant enzymes such as superoxide dismutase, and zinc deficiency impairs their synthesis, leading to increased oxidative stress. Studies have shown that diabetes is accompanied by hypozincemia and hyperzincuria. In addition zinc deficiency is more common in developing countries, where diabetes is also showing an exponential increase in prevalence.” (7)

• “The eyes are often indicators of systemic disease and are particularly vulnerable to the pathophysiological changes that occur as a result of diabetes. This article provides an overview of five main ocular complications associated with diabetes: cataract, diabetic retinopathy, central retinal vein occlusion, central retinal artery occlusion and neovascular glaucoma.”(8)

• “Macular degeneration is the leading cause of vision loss among people 50 years or older in the United States. It occurs when that part of your retina known as the macula becomes damaged and interferes with central vision. . . . Type 2 diabetes increases the risk of developing macular degeneration. Eating a healthy diet rich in the antioxidants known as lutein and zeaxanthin has been found to decrease risk for this disease.” (9)

Link between atherosclerosis and cadmium.

• “Experimental data suggest that cadmium affects several signaling pathways which may lead to endothelial dysfunction and vascular tissue damage, promoting atherosclerosis. This is further supported by epidemiological studies that have shown an association of even low-level cadmium exposure with an increased risk of clinical cardiovascular events.” (10)

• “Comparing quartile 4 with quartile 1 of blood cadmium, the odds ratio (OR) for prevalence of any plaque was 1.9 (95% confidence interval 1.6–2.2) after adjustment for sex and, age; . . . These results extend previous studies on cadmium exposure and clinical cardiovascular events by adding data on the association between cadmium and underlying atherosclerosis in humans.” (11)

• “Cadmium is considered one of the most toxic environmental substances due to its ubiquity, toxicity, and long half-life. Exposure to cadmium occurs through inhalation (particularly in active cigarette smokers), water consumption, industrial exposure, and contaminated food (Table). . . . High levels of cadmium can be found in vegetables, fruits, and grains, with the highest levels in greens and potatoes. Shellfish and organ meats contain elevated cadmium concentrations as well, and agricultural fertilizer has also been reported to contain cadmium. . . . Cadmium is associated with cardiovascular and all-cause mortality. . . . The risk of coronary artery disease (CAD)–associated mortality was also increased (HR 1.36, 95% CI 1.11-1.66).”(12)

• “The cadmium concentrations in symptomatic plaques were 50-fold higher in plaque tissue than in blood. Cadmium levels in blood and plaque correlated, also after adjustment for smoking and other cardiovascular risk factors (p<0.001). Compared with the other parts of the plaque, the cadmium content was double as high in the part where plaque rupture usually occurs. In conclusion, the results show that cadmium exposure is associated with the burden of subclinical atherosclerosis in middle-aged women with different degrees of glucose tolerance, and that the content of cadmium in symptomatic plaques in patients is related to that in blood, but much higher, and preferentially located in the part of plaque where rupture often occurs.”(13)

Link between neuropathy and cadmium.

• “Cadmium (Cd) is a heavy metal that has received considerable concern environmentally and occupationally. Cd has a long biological half-life mainly due to its low rate of excretion from the body. Thus, prolonged exposure to Cd will cause toxic effect due to its accumulation over time in a variety of tissues, including kidneys, liver, central nervous system (CNS), and peripheral neuronal systems. Cd can be uptaken from the nasal mucosa or olfactory pathways into the peripheral and central neurons; for the latter, Cd can increase the blood brain barrier (BBB) permeability. However, mechanisms underlying Cd neurotoxicity remain not completely understood. Effect of Cd neurotransmitter, oxidative damage, interaction with other metals such as cobalt and zinc, estrogen-like, effect and epigenetic modification may all be the underlying mechanisms.”(14)

Link between diabetes and Alzheimer’s Disease.

• A major symptom that Alzheimer’s disease patients and type 2 diabetes patients have in common is insulin resistance. This and other characteristics of the two diseases are reviewed in “Alzheimer’s Disease Is Type 3 Diabetes–Evidence Reviewed.”(15)

Background

Cadmium: Carcinogenic Heavy Metal

• One of three naturally occurring heavy metals not used by the body (up to atomic number 92—lead and mercury are the other two)
• In same family of the Periodic Table of the Elements as zinc and mercury, and therefore, has similar chemical characteristics

Found in mineral deposits of great commercial importance (e.g., phosphate, zinc, copper)

Concentration in phosphate deposits in the U.S. vary:

Cadmium: Routes of Exposure

Air (Inhalation)

• Cigarette smoke (first- and second-hand smoke)
• Inhaled dust and soil particles
• Inhaled flour
  Water and other beverages (Ingestion)

• Galvanized pipes (leaching of Cd from low-grade zinc coating)
• PVC pipes (leaching of Cd used as stabilizer in the manufacturing process)
• Water used in soft drinks
• Phosphate additives in soft drinks (including phosphoric acid)
  Food (Ingestion)

• Grain (e.g., wheat, rice)
• Certain vegetables and fruits (e.g., potato skins, peanuts, mushrooms, strawberries)

• Shellfish (e.g., shrimp and oysters) and contaminated fish
• Organ meats (e.g., liver, many sausages and frankfurters)
• Sugar (from sugar beets and sources close to the ground, including the lower portion of sugar cane)
• Processed foods (mostly those containing phosphate additives)
  Skin contact (Dermal Absorption)

• Gardening (e.g., in phosphates added to potting soil)
• Jewelry (e.g., in children’s jewelry from overseas)
• Makeup (still used in some countries for its red color)
• Cadmium: Effect on the Human Body

• Accumulates primarily in the liver, kidneys, pancreas, lungs, and bones, and to a lesser extent in thyroid, prostate, adrenal glands, and other vital organs.
• Goes unnoticed until critical organ-specific threshold concentrations are reached and symptoms begin to develop
• Typical “American” diet—symptoms begin to appear at around age 50
• Typical “Hispanic” diet— symptoms begin to appear at around age 40
• Causes organs dysfunction, leads to cancer
• Depletes the body of zinc, replaces zinc and often causes steric hindrance due to its larger atomic radius(161 picometers [pm], compared to 142 pm for zinc)
• Causes increased permeability of intestinal lining (leaky gut), endothelium in blood vessels (contributesto atherosclerosis) and the blood-brain barrier (leaky brain)
• Resulting adverse impacts are both direct and indirect, and often involve the body’s response tosequester and eliminate cadmium
• Diabetes and pancreatic cancer
• Kidney disease and kidney cancer
• Liver disease, gall stones, and liver cancer
• COPD and other lung diseases, lung cancer
• Osteoarthritis, osteoporosis, and fragility of the bones
• Impaired thyroid function and associated hormone-related diseases,
• Enlarged prostate and prostate cancer
• Breast cancer
• Stomach cancer
• Alzheimer’s Disease (Type 3 Diabetes)
• Leads to zinc deficiency, impaired immune system, and increased susceptibility to bacterial/viralinfections, and all types of cancer
• Autoimmune diseases (e.g., Celiac Disease, Lupus, Multiple Sclerosis, Hashimoto’s Disease)
• Weight gain (thyroid, beta cells of the Islets of Langerhans of the pancreas)Cadmium: Carcinogenic Heavy Metal In the Food Chain

• Contaminant in phosphate fertilizers
• Crop uptake from contaminated fields
• Wheat and rice are efficient at concentrating cadmium on the inside of the grain (white), while zinc is inhigher concentration on the outside (whole grain wheat and rice are less toxic than white)
• Beets are used to phytoremediate contaminated soils because of their efficient uptake of Cd
• 56% of the sugar production in the U.S. is from sugar beets
• Generally, anything that grows in the ground or on the ground will be high in cadmium
• Generally, anything that grows on trees, long vines, or tall stalks will be low in cadmium (Cd remains inroots, vines, leaves, stalks, etc.)
• Runoff from fields contaminates rivers and other receiving waters, while groundwater is contaminatedthrough infiltration
• Concentration in shellfish from the Gulf of Mexico is about 1,000 times the concentration found in beef,chicken or pork (other than organ meats); about 100 times for shellfish off the west coast of the U.S.
• Organ meats (Cd accumulates in the organs of cattle, poultry, and swine as in humans)

Importance of Zinc

• Essential for a healthy immune system
• Essential for healing
• Essential for proper brain function
• Involved in over 300 enzymatic reactions in the body
• Included in every strand of DNA in every cell of the body
• Essential for strong bones
• Essential for reproduction
  • A man’s semen has a zinc concentration 100 times greater than any other fluid in his body
  • A woman’s placenta has a zinc concentration 1,000 times greater than any other tissue in her body
• A newborn is normally zinc-rich and virtually free of cadmium
• Concurrent ingestion of zinc and cadmium reduces cadmium assimilation
• Zinc has a 78-day biological half-life compared to up to 30 years for cadmiumCadmium, Zinc Deficiency, COVID-19, and Gestational Diabetes During Pregnancy

  A substantial fraction of the zinc ingested by a pregnant woman is diverted to the fetus and its environment, potentially leaving the rest of the woman’s cells in a zinc-deficient state. This may account for the fact that the SARS-CoV-2 infection rate for pregnant women is high, and their symptoms are more severe than those of women who are not pregnant. The CDC reports, “Based on what we know at this time,pregnant people might be at an increased risk for severe illness from COVID-19 compared to non-pregnant people.”16 “An MMWR [Morbidity and Mortality Weekly Report] study suggests that pregnant women with COVID-19 are more likely to be hospitalized and are at increased risk for intensive care unit (ICU) admission and receipt of mechanical ventilation than nonpregnant women.”(17)

  The developing fetus and placenta act as a zinc sink, depleting the pregnant woman’s zinc reserves, leaving her susceptible to COVID-19 and other diseases. I suggest that gestational diabetes is one of these other diseases. It is widely accepted as a pregnancy-related issue that typically resolves itself with time after giving birth. According to the Mayo Clinic, one of the gestational diabetes risk factors is being of a “nonwhite race,” which includes African-Americans and Hispanics,18 two groups that are particularly vulnerable to SARS-CoV-2 infection, most likely stemming from cadmium in their diets and the resulting zinc deficiency. The issue of cadmium in the diets of African-Americans and Hispanics is not only ethnic but also economic, because many foods that contain relatively high cadmium concentrations (e.g., wheat products, rice products, frankfurters, soft drinks, cereals, peanut butter, sugary treats) are relatively inexpensive.

Being a Black or Hispanic pregnant woman during the COVID-19 pandemic is not a good idea. “Pregnant women who are Black or Hispanic appear to be disproportionately affected by infection with the COVID-19 virus. Pregnant women who have underlying medical conditions, such as diabetes, also might be at even higher risk of severe illness due to COVID-19.”19 This is zinc deficiency on top of zinc deficiency. In other words, Blacks and Hispanics are already groups that are more likely to be zinc deficient, and further depleting zinc reserves because of a pregnancy makes pregnant Black and Hispanic women particularly susceptible to infection by the SARS-CoV-2 virus and prone to experience more severe symptoms.

Conclusion

Individuals suffering from type 2 diabetes, diseases commonly referred to as complications of diabetes, and COVID-19 are likely to be more susceptible to these diseases due to chronic cadmium poisoning and the zinc deficiency it produces. Many studies have focused on small, specific aspects of this problem, but few have examined the problem as a whole to give the “big picture” so that it can be addressed. It is my hope that this article will serve to stimulate personal curiosity and research on cadmium toxicity and our chronic cadmium exposure through the food supply. Adjustments in lifestyle and diet can help reduce exposure and lessen the risk of being diagnosed with the diseases mentioned here and many others, including numerous forms of cancer, that were not discussed in this article.

References

1. “Zn2+ Inhibits Coronavirus and Arterivirus RNA Polymerase Activity In Vitro and Zinc Ionophores Block the Replication of These Viruses in Cell Culture,” Velthuis, A., et al., PLoS Pathogens, 2010 Nov 4, 6(11),
   https://pubmed.ncbi.nlm.nih.gov/21079686/fbclid=IwAR32x2hwLPL_fVEUrNGHZRIa5xRCEDHZ H1FeDe8bvC_dzgI3zRwEaRRDCUU 
2. “Older Adults,” Center for Disease Control and Prevention (CDC), Coronavirus Disease (COVID-19),https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/older-adults.html
3. “Risk of Death from COVID-19 Four Times Greater for Those with Diabetes,” Healthline,https://www.healthline.com/health-news/covid-19-impact-on-diabetes-hospitalizations
4. “If You Are Immunocompromised, Protect Yourself From COVID-19,” Center for Disease Control and Prevention (CDC), Coronavirus Disease (COVID-19), https://www.cdc.gov/coronavirus/2019- ncov/need-extra-precautions/immunocompromised.html
5. “Cadmium, Diabetes and Chronic Kidney Disease,” J. Edwards and W. Prozialeck, Toxicology and Applied Pharmacology. 8/1/2009; 238(3): 289–293,https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2709710/
6. “Zinc in the eye,” Survey of Ophthalmology, Sep-Oct 1982;27(2):114-22, Karcioglu, Z.,https://pubmed.ncbi.nlm.nih.gov/6755784/
7. “Effects of zinc supplementation on diabetes mellitus: a systematic review and meta-analysis,” R. Jayawardena, et al., Diabetology & Metabolic Syndrome, 2012; 4: 13,https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3407731/
8. “Ocular complications associated with diabetes mellitus,” S. Watkinson and R. Seewoodhary, Nursing Standard, 2008 Mar 12-18;22(27):51-7, https://www.ncbi.nlm.nih.gov/pubmed/18405017
9. “Does having type 2 diabetes have anything to do with having macular degeneration?” dLife, 4/13/2017, https://dlife.com/qa/type-2-diabetes-related-to-macular-degeneration/
10. “Low-Level Cadmium Exposure and Atherosclerosis,” Diaz, D., et al., Metals and Health, March 23, 2021, https://link.springer.com/article/10.1007/s40572-021-00304-w

11. “Cadmium exposure and atherosclerotic carotid plaques–Results from the Malmö diet and Cancer study,” Fagerberg, B., et al., Environmental Research, Volume 136, January 2015, Pages 67-74,
    https://www.sciencedirect.com/science/article/pii/S0013935114004034?via%3Dihub
12. “Metal pollutants and cardiovascular disease: Mechanisms and consequences of exposure,” Solenkova, N., et al., Curriculum in Cardiology,https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4254412/pdf/nihms616174.pdf
13. “Is Cadmium Exposure Associated with the Burden, Vulnerability and Rupture of Human Atherosclerotic Plaques?” Bergström, G., et al., PLOS ONE, March 27, 2015,https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0121240
14. “Cadmium and Its Neurotoxic Effects,” B. Wang and Y. Du, Oxidative Medicine and Cellular Longevity, Volume 2013, Article ID 89803,https://downloads.hindawi.com/journals/omcl/2013/898034.pdf
15. “Alzheimer’s Disease Is Type 3 Diabetes–Evidence Reviewed.” (S. de la Monte and J. Wands,https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2769828/
16. “If You Are Pregnant, Breastfeeding, or Caring for Young Children,” Center for Disease Control and Prevention, Coronavirus Disease 2019 (COVID-19), https://www.cdc.gov/coronavirus/2019- ncov/need-extra-precautions/pregnancy-breastfeeding.html
17. “Data on COVID-19 during Pregnancy,” Center for Disease Control and Prevention, Coronavirus Disease 2019 (COVID-19), https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/special- populations/pregnancy-data-on-covid-19.html
18. “Gestational Diabetes,” Mayo Clinic, https://www.mayoclinic.org/diseases-conditions/gestational- diabetes/symptoms-causes/syc-20355339
19. “Pregnancy and COVID-19: What are the risks?”, Mayo Clinic, https://www.mayoclinic.org/diseases- conditions/coronavirus/in-depth/pregnancy-and-covid-19/art- 20482639#:~:text=Pregnant%20women%20who%20are%20Black,COVID%2D19%20virus