Zinc Away Your Inflammation

When you put your hand into your pants pocket and shake it around, you can hear the jingling of loose change. No change, no jingle. You have identified a deficit. It’s not that easy with some nutrient deficits. Zinc is one of them. Although zinc levels are low in some disorders, the most reliable method for diagnosing zinc deficiency is a positive response to zinc supplementation.  Most of the zinc in the body is held in skeletal muscle and bone, so we’re not likely to notice a shortage right away because there are no signs. Growth retardation, low insulin levels, anorexia, mental fog, rough skin, and decreased thyroid function are symptoms, but these may also be related to other causes.  Worldwide, zinc deficiency is not uncommon, though it is rare in the United States. Nonetheless, it’s a good idea to make sure your buckets are filled.

Functionally, zinc is part of more than a hundred different enzymes that catalyze important chemical reactions. Structurally, it helps to build proteins and cell membranes. In fact, there is a component call a zinc-finger that stabilizes protein complexes and helps to regulate gene expression by binding to DNA. Loss of this mineral from the cell membrane opens it to insult from oxidative damage.

What was once considered hyperbolic in promoting zinc as treatment for illnesses such as colds and related respiratory concerns is now being examined as practicable. One of the body’s protective reactions to attack by irritation, infection or injury is inflammation, characterized by redness, swelling, discomfort and, occasionally, loss of function.  Inflammation will activate platelets and attract monocytes/macrophages to swallow up harmful foreign particles. If it becomes chronic, inflammation can grow increasingly destructive of healthy tissue while it tries to heal that tissue already under attack. Out-of-control inflammation can become a threat to life.

As an intermediary in the inflammatory process, zinc helps to control the ardor with which the body fights infections and other physiological troublemakers. Current research has learned that zinc modulates inflammation by connecting with, and impeding, the function of specific protein instigators. This work has focused on the context of sepsis, which is a systemic response to infection that can be devastating enough to cause death. This septic condition has a name—Systemic Inflammatory Response Syndrome (SIRS). What often follows is depressed organ function—Multiple Organ Dysfunction Syndrome (MODS)—and consequent death.  Nuclear factor-kappa Beta, known as NF-kB, is a protein that acts as a transcription factor, and is especially active in responses to stressors like free radicals, radiation, bacterial and viral antigens, and cytokines. The latter initiate an immune response and include chemicals such as interferons and interleukins. In NF-kB is not kept in check, it can wreak more havoc than Attila the Hun.

In the presence of adequate zinc levels, NF-kB activity is downregulated and pro-inflammatory response is controlled (Liu, 2013). This doesn’t necessarily mean that zinc is a cure-all, since its paucity will telegraph other mineral insufficiencies, as well. Laboratory animals suffering induced zinc deficiency while being exposed to sepsis have responded with systemic inflammation and subsequent damage to vital organs, resulting in predicted mortality. In these instances NF-kB was overexpressed, appearing especially active in the respiratory system. Zinc supplementation administered immediately prior to the initiation of sepsis was able to stave off morbidity and mortality (Bao, 2010).

When a pathogen attacks the body, monocytes are the first line of defense. One job is to awaken the sleeping giant and to get the immunity ball rolling. This is when NF-kB enters the nucleus and unlocks the door so zinc can cross the cell membrane. When the zinc merges with a protein ally, it calms down the NF-kB to prevent runaway inflammation. The balance of activity in this drama is delicate, meaning that more (zinc) is not necessarily better. Even a modest deficiency, though, will invite immune dysfunction and increase the chance for infection from whatever is floating around.  The medical, social and academic venues that host crowds of people, such as hospitals, churches and schools can test your susceptibility, which increases with age by virtue of failure to tend to personal needs for lack of motivation and, perhaps, wherewithal.

Though zinc toxicity can be caused by drinking from galvanized containers, it’s more likely to come from overzealous supplementation or from ingesting multiple sources that contain zinc. That includes food as well as supplements. Abdominal pain, diarrhea, nausea and vomiting are the initial signs of overdose. Chronic excess will interrupt copper metabolism and disrupt a raft of physiological functions that include making red blood cells and myelin, and regulating some gene functions. Adults need only eleven milligrams a day; forty is pushing the envelope. Half-dozen oysters provide more than seventy-five milligrams.  Even denture adhesives contain enough zinc to cause symptoms of toxicity if combined with dietary and supplement sources. Taking zinc with a quinolone or tetracycline antibiotic will reduce the absorption of both the zinc and the drug. This also will happen with some medications used for rheumatoid arthritis.  Nasal sprays containing zinc can cause irreversible loss of smell, which can be dangerous if you can’t detect a gas leak. Being stored throughout the body, zinc is a permanent resident; so once again, it’s a matter of balance.

Bao B, Prasad AS, Beck FW, Snell D, Suneja A, Sarkar FH, Doshi N, Fitzgerald JT, Swerdlow P. Zinc supplementation decreases oxidative stress, incidence of infection, and generation of inflammatory cytokines in sickle cell disease patients. Transl Res. 2008 Aug;152(2):67-80.

Bao S, Liu MJ, Lee B, Besecker B, Lai JP, Guttridge DC, Knoell DL. Zinc modulates the innate immune response in vivo to polymicrobial sepsis through regulation of NF-kappaB. Am J Physiol Lung Cell Mol Physiol. 2010 Jun;298(6):L744-54.

Barceloux DG. Zinc. J Toxicol Clin Toxicol. 1999;37(2):279-92.

Besecker BY, Exline MC, Hollyfield J, Phillips G, Disilvestro RA, Wewers MD, Knoell DL. A comparison of zinc metabolism, inflammation, and disease severity in critically ill infected and noninfected adults early after intensive care unit admission. Am J Clin Nutr. 2011 Jun;93(6):1356-64.

Freake HC, Govoni KE, Guda K, Huang C, Zinn SA. Actions and interactions of thyroid hormone and zinc status in growing rats. J Nutr. 2001 Apr;131(4):1135-41.

Lang C, Murgia C, Leong M, Tan LW, Perozzi G, Knight D, Ruffin R, Zalewski P. Anti-inflammatory effects of zinc and alterations in zinc transporter mRNA in mouse models of allergic inflammation. Am J Physiol Lung Cell Mol Physiol. 2007 Feb;292(2):L577-84.

Liu MJ, Bao S, Gálvez-Peralta M, Pyle CJ, Rudawsky AC, Pavlovicz RE, Killilea DW, Li C, Nebert DW, Wewers MD, Knoell DL. ZIP8 Regulates Host Defense through Zinc-Mediated Inhibition of NF-κB. Cell Rep. 2013 Feb 8. pii: S2211-1247(13)00016-8.

Knoell DL, Liu MJ. Impact of zinc metabolism on innate immune function in the setting of sepsis. Int J Vitam Nutr Res. 2010 Oct;80(4-5):271-7.

Lang C, Murgia C, Leong M, Tan LW, Perozzi G, Knight D, Ruffin R, Zalewski P. Anti-inflammatory effects of zinc and alterations in zinc transporter mRNA in mouse models of allergic inflammation. Am J Physiol Lung Cell Mol Physiol. 2007 Feb;292(2):L577-84.

O'Dell BL. Role of zinc in plasma membrane function. J Nutr. 2000 May;130(5S Suppl):1432S-6S.

Overbeck S, Rink L, Haase H. Modulating the immune response by oral zinc supplementation: a single approach for multiple diseases. Arch Immunol Ther Exp (Warsz). 2008 Jan-Feb;56(1):15-30.

Prasad AS. Zinc: role in immunity, oxidative stress and chronic inflammation. Curr Opin Clin Nutr Metab Care. 2009 Nov;12(6):646-52. doi: 10.1097/MCO.0b013e3283312956.

Sandström B. Micronutrient interactions: effects on absorption and bioavailability. Br J Nutr. 2001 May;85 Suppl 2:S181-5.

Vasto S, Mocchegiani E, Candore G, Listì F, Colonna-Romano G, Lio D, Malavolta M, Giacconi R, Cipriano C, Caruso C. Inflammation, genes and zinc in ageing and age-related diseases. Biogerontology. 2006 Oct-Dec;7(5-6):315-27.

Vasto S, Mocchegiani E, Malavolta M, Cuppari I, Listì F, Nuzzo D, Ditta V, Candore G, Caruso C. Zinc and inflammatory/immune response in aging. Ann N Y Acad Sci. 2007 Apr;1100:111-22.

*These statements have not been evaluated by the FDA. These products are not intended to treat, diagnose, cure, or prevent any disease.