Nutrient of the Month: Zinc

Zinc is one of the greats: essential for protein synthesis and the growth, integrity, repair, and maintenance of intestinal, connective, nervous, epithelial, and other tissues, it is also crucial in immune cell function and balance, creation of red blood cell heme, taste, smell, and vision, the function and structure of myriad enzymes, blood clotting, and thyroid hormone production and regulation. It is the most abundant metal within cells (found mainly in muscle and bone) and the second most abundant trace metal in the body. In the brain, it concentrates in the hippocampus, amygdala, cerebral cortex, thalamus, and olfactory cortex—areas central to higher brain function, alertness, and the stress response. Foods that provide relatively generous amounts of zinc include oysters and other shellfish, wheat germ, meat, sesame seeds and tahini, watermelon seed, pumpkin seed, hemp seed, flaxseed, poppy seed, dandelion greens, wheat bran, cocoa powder, peanuts, pine nuts, other nuts and seeds, whey, rice bran, wild rice, spinach, collards, cucumbers, asparagus, tomatoes, and spices like chervil, cardamom, basil, celery seed, thyme, parsley, and mustard seed.

Populations at risk for zinc insufficiency include children, teenagers, pregnant and lactating women, older people (due to reduced intake and absorption), vegetarians, smokers, post-bariatric surgery patients, and those taking opioids. Those with inflammatory bowel disease and other conditions of increased gut permeability, skin problems, sickle cell disease, atopy and/or allergy, kidney disorders, cancer, tuberculosis, and rheumatoid arthritis may also have a higher zinc requirement. Some of the more common manifestations of zinc insufficiency include reduced sensory sensitivity, hair loss, weight loss, glucose intolerance, diarrhea, skin problems, poor wound healing, and reduced sperm production. Acids (e.g., gastric or vinegar) tend to aid zinc absorption while other minerals (especially iron and excess copper), fiber, and excess alcohol consumption can interfere with zinc metabolism. Zinc may have interactions with diabetes drugs, penicillamine, quinolone and tetracycline antibiotics, chelating agents, gastric acid suppressors, diuretics, and other medications, sometimes depending upon genetic variation. Zinc toxicity is relatively rare, but as minerals influence each other’s absorption and metabolism, it is important to receive sufficient amounts of each and avoid excessive amounts of any single one unless recommended by a health care practitioner.

Functional Neurologist Dale Bredesen, MD, has emphasized zinc’s importance in cognitive function, and how its deficiency induces insulin resistance, affects hormone signaling, and facilitates inflammation and autoimmunity. He mentions the zinc metalloproteinase ADAM10, which may cleave amyloid precursor protein without producing toxic amyloid, and has identified a distinctive subtype of Alzheimer’s disease showing very low serum zinc levels (while pointing out that red blood cell zinc is a more accurate clinical test). A 2013 study found that zinc supplementation protected cognitive function in older individuals; this article suggests that it may achieve this in part by protecting brain neurons from glutamate-induced excitotoxicity (which has been associated with stress and cognitive dysfunction), and also notes that amyloid plaques may bind zinc and render it unavailable. Maintaining sensory sensitivity is crucial to successful cognitive aging, and zinc supplementation may help retain the sense of taste in older people. The level of zinc in the visual retina decreases with age, and as zinc level in the exquisitely delicate yet protective retinal pigment epithelium affects risk for age-related macular degeneration (AMD), it is included in the AREDS formulations studied in AMD.

Here are some other research findings regarding zinc:

  • As in IBD and AMD (above), zinc plays a central role in building epithelial barriers and their intercellular tight junctions, and zinc insufficiency also relates to atopic dermatitis (eczema), healing pressure ulcers of the skin, and chronic obstructive pulmonary disease (COPD); early research also suggests it may aid the mouth’s epithelial barrier.

  • Recent work in human stem cells suggests that zinc (as sulfate) may improve genetic expression of telomerase and telomere lengthening; interestingly, treated stem cell populations also showed a lower percentage of senescent (aged) cells, which was associated with different methylation patterning.

  • Breaking research has found that obese persons have lower serum levels of zinc as well as a zinc-containing adipokine known to regulate fat distribution and lipid mobilization, which may reflect altered zinc metabolism in obesity.

  • Zinc is an important factor in bone formation and mineralization.

  • Zinc status affects the activity of antioxidant enzymes like the Nrf2 master regulator of antioxidant enzymes, metallothionein, glutathione enzymes, and hemeoxygenase, and while its deficiency increases oxidative stress, it can also have pro-oxidant properties in excess.

  • Lack of available zinc can limit mitochondrial biogenesis, and insufficient as well as excessive zinc can hamper mitochondrial energy production.

  • Dysregulated zinc signaling may influence development of inflammation, autoimmunity, and allergy, and in immune cells taken from atopic individuals, zinc exposure moderated the immune response by altering cytokine balance and increasing the number of immune regulatory T cells—actions that would tend to reduce the atopic response without negatively affecting immunity.

  • In one study, older adults with the highest zinc intakes were 30-50% less likely to become depressed compared to those at the lowest intakes, which may relate to the effects of zinc signaling on synaptic plasticity and neurotransmitter receptor function.

  • Zinc supplementation was associated with notable drops in C-reactive protein (CRP) levels in healthy persons and kidney patients, and in subjects with chronic liver disease (who typically experience elevated oxidative stress and inflammation), circulating zinc levels correlated negatively with CRP levels as well as markers of oxidative stress.

  • Zinc status is generally though not conclusively related to male fertility.

  • Zinc plays multiple roles in insulin production, secretion, and sensitivity, and zinc supplementation has improved insulin sensitivity in obese adults; in prediabetic persons, higher serum zinc was associated with greater insulin sensitivity.

  • A 2018 meta-analysis cautiously concluded that blood levels of zinc may relate to measures of intelligence in children, though confirmation may be needed.

  • In meta-analysis, hypertensive adults showed significantly lower serum zinc levels, though the significance of this is not certain.

  • Somewhat like iron within hemoglobin or magnesium within chlorophyll, zinc nestles in the center of zinc finger proteins, which aid gene expression and silencing. Over 3000 human zinc finger proteins have been identified, and they are estimated to be found at 3% of human genes. Other zinc proteins facilitate DNA repair, production of enzymes and structural proteins, and molecular transport and storage, and zinc is also a component in some sirtuins and related histone deacetylase (HDAC) enzymes whose activity helps regulate cellular aging processes.

Particular genetic polymorphisms may affect zinc transporter function as well as metabolic requirements for zinc, and through them, the potential for deficiency and dysfunction.

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