Zinc has been studied for years for its implications in kidney disease. In fact, many researchers have pointed to zinc deficiency as one of the underlying causes of the worsening of kidney disease. We can explore even more upstream and understand some of the factors that result in zinc deficiency in the first place. So let’s discuss zinc and kidney disease.

Zinc and kidneys

Zinc: The Micromineral 

Zinc is classified as a trace mineral because it’s typically needed in small doses to exert its biological effects. This nutritional mineral is involved in functions that include glycolysis (converting glucose into energy), digestion especially protein breakdown, bone formation, DNA metabolism, alcohol metabolism, angiotensin conversion, heme biosynthesis, and as an antioxidant protecting from reactive oxygen species (ROS) and the resulting cellular damage from inflammation. In fact, it’s so important, that it is the third most relevant intracellular ion (behind magnesium and potassium). 

In addition, there are over 200 metal-containing enzymes, called metalloenzymes, responsible for catalyzing a variety of crucial reactions throughout the cells in our bodies. In fact, 20 distinct biological functions are associated with zinc metalloenzymes.

Zinc Absorption and Deficiency 

Zinc is primarily absorbed in the small intestines via mechanisms called transcellular and paracellular transport. That means it can passively diffuse through tight junctions or by carrier mediated transporters. The latter means that absorption of zinc can be influenced by genetic SNPs which can result in decreased zinc transport and subsequently increased risk for deficiency

Furthermore, absorption is reduced with aging and maldigestion/low stomach acidity. Drugs that inhibit stomach acid production, such as proton pump inhibitors (PPIs) and H2 antagonists (H2A) are thought to cause zinc depletion by reducing stomach acidity. This effect can be reversed by addressing the gut dysfunction through the 5R protocol.   

Other drugs that may alter zinc status include angiotensin-converting enzyme inhibitors (ACEi), aspirin, thiazide and loop diuretics, long-term use of steroids, and fluoroquinolone, penicillamine, and tetracycline antibiotics. The degree of depletion is dependent on multiple factors, including individual differences, dose and length of therapy.   

Assessment of zinc status through laboratory testing has been criticized as being unreliable. However, coupled with a comprehensive assessment of symptoms it can be very helpful in identifying mineral deficiency. Examples of symptoms of zinc deficiency include loss of/diminished taste and/or reduced sense of smell, frequent colds, slow wound healing, loss of appetite, presence of or worsening of acne/rosacea. 

Zinc and kidney disease

The prevalence of zinc deficiency in chronic kidney disease (CKD) patients is well documented. Furthermore, zinc nutritional status is also altered in obesity. In fact, fasting plasma zinc concentrations are inversely correlated to BMI and plasma glucose levels.

Several inflammatory mechanisms are associated with zinc depletion, while adequate levels of zinc decreases formation of reactive oxygen species (ROS). ROS activate nuclear factor-κB (NF-κB) which induces the generation of inflammatory cytokines and adhesion molecules associated with various types of kidney diseases, including IgA nephropathy.

Superoxide dismutase (SOD), and enzyme which converts the oxidative superoxide into an inert product, hydrogen peroxide. The SOD enzyme requires zinc in order to work efficiently, and zinc deficiency reduces the activity of the enzyme and has been shown to increase inflammation-induced kidney damage, in part via this mechanism. 

Another interesting associations include the impact of zinc deficiency on increased calcification in the development of kidney stones. 

Zinc also plays an important role in protecting the kidneys from environmental toxins, especially heavy metal. Heavy metal toxicity, such as lead and cadmium, is significantly associated with kidney disease. Studies have shown that a deficiency in zinc, as well as other essential metals such as calcium or iron, can lead to increased absorption and toxicity of lead and cadmium. Therefore, providing yet another potential benefit of ensuring zinc repletion to protect against metal toxicity and its impact on kidney, as well as overall health.

Implications of zinc deficiency in cardiovascular and metabolic disease associated with KD

Zinc impacts kidney disease via indirect associations as well. Since cardiovascular disease (CVD) and diabetes are comorbid conditions associated with kidney disease, it makes sense that factors that impact them will also impact kidney disease. 

It’s worth noting that various inflammatory markers that are triggered by deficiency of zinc, such as transcription of NF-κB, rise in IL-6, IL-2, and TNF-α, are associated with inflammatory/immune response that leads to systemic inflammation including atherosclerosis (vascular disease), a known complication of CKD. 

Zinc has some interesting effects on blood lipids, including low density lipoproteins (LDL) and triglycerides (TG). Dyslipidemia is associated with increased risk of CVD. Zinc deficiency has also been associated with elevations in TG. Furthermore, maintaining adequate levels of zinc has a protective effect against atherosclerosis by inhibiting the oxidation of LDL by cells or transition metals. 

In addition, there are multiple mechanism where zinc impacts metabolic disease. Interestingly, zinc is essential for insulin synthesis and release, and deficiency impairs the release of insulin contributing to insulin resistance and elevations in blood sugar. 

Another hormone responsible for feeling of satiety (fullness after eating) is leptin, which is produced by fat cells. Leptin resistance is associated with overeating and obesity. Zinc depletion may impact leptin indirectly because leptin secretion is regulated by insulin. Furthermore, deficiencies in zinc impact the activity of peroxisome proliferator-activated receptors (PPARs). PPARs are associated with multiple metabolic pathways of lipid and glucose metabolism. They initiate cascade of mechanisms which activate atherogenesis, and are, therefore, central to metabolic disease, CVD, and kidney disease.

Food-based sources of zinc

Red meat, organ meats, and shellfish are considered the best sources of zinc, with levels significantly higher than vegetarian sources. Although not as high as animal sources, nuts and seeds are good sources of zinc. Although whole grains are good sources as well, refined grains are not because zinc is lost when the bran and germ coating is removed in processing. Unfortunately, although an essential part of a healthy diet, fruits and vegetables are not significant sources of this nutrient. Not surprisingly, vegetarians are at increased risk for zinc deficiency and should be screened routinely. 

There are food interactions that reduce absorption of zinc. Phytic acid, naturally found in grains, may inhibit the absorption of zinc. Therefore it’s advisable to soak grains for 8-24 hours in filtered water and 1 tablespoon of lemon juice or apple cider vinegar prior to cooking to reduce levels of phytic acid and enhance absorption of zinc and other minerals. It’s also interesting to note that absorption of zinc is reduced by the intake of dairy, likely due to the high calcium content which is known to interfere with zinc uptake. 

Supplementing zinc is a good option in cases of deficiency. There are multiple compounds available on the market. We recommend using zinc picolinate or zinc citrate. Zinc carnosine is useful as part of gut restoration protocol to address GERD and as part of a PPI tapering protocol. Note that the dosage and length of therapy should be customized to individual needs and tracked by your functional medicine provider or nutritionist. If you notice a metallic taste in your mouth, have your healthcare provider check your zinc levels to ensure they are not too high or toxic. 

The Bottom Line

There are multiple suggested mechanisms contributing to the impact of zinc deficiency on kidney health. It’s no surprise considering the various mechanisms that involve zinc. It’s important to consider the impact of diet, medications, dysbiosis and intestinal permeability on zinc status and subsequently on protecting the kidneys from disease.