ZINC AND INFLAMMATION

ZINC AND INFLAMMATION
Age-Related Zinc Deficiency May Contribute to Chronic Disease Risk

A recent study published in the Journal of Nutritional Bio­chemistry found a biological explanation for age-related reductions in zinc status that may lead to impaired immune system functioning and systemic inflammation, which are contributing factors to chronic diseases. The study, which used cell cultures and a mouse model, suggests that improv­ing zinc status through diet and supplementation may be a viable strategy for reducing the risk of inflammatory diseases.

“When the body has insufficient access to zinc
, it’s hit on many levels due to the many ways in which zinc typically func­tions to protect the body,” explains Ellen B. Fung, PhD, RD, CCD, an associate research scientist at Children’s Hospital and Research Center in Oakland, California. “First, zinc plays a significant role as an antioxidant in the body. Therefore, in a zinc-deficient state, there will be an excess of oxidants pres­ent, leading to increased DNA damage. In addition, zinc is a cofactor for RNA and DNA polymerases, which aid in the usual repair mechanisms. When these systems don’t function properly, there will be increased damage. Finally, zinc aids in modulating DNA repair and damage proteins. ... In a deficient state, these systems also are in a state of disarray and lead to increased DNA damage.”

Researchers from Oregon State University examined the effects of zinc deficiency and age on inflammatory responses in both a cell culture model and an aged mouse model. One aspect of the study compared groups of mice fed two different amounts of zinc in their diets. The group receiving zinc sup­plementation showed fewer age-related increases in markers of inflammation. Though inflammation is essential for tissue repair and recovery from infections and injuries, uncontrolled systemic inflammation leads to the excessive formation of free radicals and subse­quent damage to body tissues, a cascade of events that contributes to the development of autoim­mune diseases and several chronic diseases.

“The link that Dr [Emily] Ho has made between zinc deficiency and DNA damage, and now sys­temic inflammation, explains much of what we see on a cellular or whole-animal level,” Fung says. “For example, the root cause of the link between immune function deficits—why you get sick more readily as you age—and zinc deficiency may be the increased methylation of zinc transporters, causing them not to function properly. … This leads to decreased zinc inside an immune cell and increased inflammation—a bad situation.

If the results can be translated to humans, they would suggest that “we can override the age-related deficits by supplementing with zinc,” according to Fung.

Study Details

In the in vitro cell model, human monocytes were grown in zinc-deficient or -adequate media for up to 14 days. Mac­rophages were then treated with 0, 10, or 100 ng/mL of LPS, the major structural component of the outer wall of gram-negative bacteria that initiates inflammatory responses. Cells grown in zinc-adequate media had a significant decline in zinc status after exposure to LPS. However, cells grown in zinc-deficient media had significantly lower zinc status both pre- and post-LPS exposure compared with those grown in zinc-adequate media. In addition, zinc deficiency was associ­ated with an increase in age-related inflammation as mea­sured by expression of tumor necrosis factor-alpha and interleukin-1-beta, cytokines that are important mediators of the inflammatory response.

In the animal model, mice aged 2 to 26 months were fed a standard rodent diet, a zinc-adequate diet (30 mg/kg of zinc), or a zinc-supplemented diet (300 mg/kg) for three weeks. Age-related declines in immune cell intracellular zinc content were associated with an increase in markers of inflammation. In addition, age-related environmental changes in gene expres­sion led to alterations in zinc transport mechanisms, including an increase in DNA methylation and histone modifications.

What leads to age-related changes in zinc status? “With age, the ability to absorb and utilize zinc is compromised, though we don’t know why it isn’t well absorbed,” notes Emily Ho, PhD, lead study author and a micronutrient expert at Oregon State University.

Making matters worse, many older adults don’t consume enough zinc through their diet or supplements. According to National Health and Nutrition Examination Survey (NHANES) data from 2001-2002, 30% of men and 36% of women over the age of 71 consume less than the Estimated Average Require­ment for zinc.3 Even those who consume supplements may still fall short. NHANES III data found that 35% to 45% of elderly adults had inadequate dietary intakes of zinc, and even with a combination of diet and supplement use, 20% to 25% still fell short on their zinc intake.

Additionally, data from NHANES III (1988-1994) found that older adults (aged 60 or older) from food-insufficient house­holds have significantly lower intakes of zinc (less than 50% of the Recommended Daily Intake) compared with those from food-sufficient households,5 suggesting that access to food also may be a factor in zinc intake.

Sara A. Blackburn, DSc, RD, an associate professor of clini­cal nutrition at Indiana University-Purdue University Indianapo­lis, has observed this pattern of low zinc intake in older people. “I’ve seen zinc-poor diets in many adult patients with a chronic disease such as diabetes,” she says.

How Much Zinc?

If a person’s ability to absorb zinc declines with age, should he or she consume more of this mineral? “We don’t have a great biomarker for zinc deficiency in humans and therefore just meeting the DRI [Dietary Reference Intake] is a good place to start until more research answers this question,” Ho says.

In addition to ensuring adequate intake, Blackburn sug­gests that a thorough physical examination be conducted by the appropriate physician, paying particular attention to no healing wounds and the skin’s appearance in case there are signs of zinc deficiency.

Fish and meat are among the top sources of zinc. The bio­availability of zinc in some plant-based foods is lower than zinc from animal foods due to phytates that bind zinc and remove it from the body.

Meeting Daily Requirements

The rapid growth of the older population makes preventing age-related diseases a paramount concern. And if the results of this study prove any indication in humans, honing in on zinc status may be particularly important as a measure of preven­tion. Age-related epigenetic decline in zinc status may contrib­ute to both impaired immune system functioning and chronic inflammation and, subsequently, related health problems.

Ho recommends seniors take a multivitamin that contains the Recommended Dietary Allowance (RDA) of zinc. “Zinc is a great antioxidant. It helps with repair systems within the body. Zinc is involved in a lot of the processes that fix DNA,” says Ho, who believes future research should examine biomarkers for zinc deficiency and help determine whether the RDA for zinc is adequate for the elderly.

All Fitness __  ZINC AND INFLAMMATION

— Marie Spano, MS, RD, CSCS, CSSD, is a freelance writer and owns a sports nutrition and nutrition communications consulting company.

References

1. Perry VH. The influence of systemic inflammation on inflam­mation in the brain: implications for chronic neurodegenerative disease. Brain Behav Immun. 2004;18(5):407-413.

2. Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med. 2005;352(16):1685-1695.

3. Moshfegh A, Goldman J, Cleveland L. What We Eat in America, NHANES 2001-2002: Usual Nutrient Intakes From Food Compared to Dietary Reference Intakes. Washington, DC: US Department of Agriculture Agricultural Research Service; 2005.

4. Ervin RB, Kennedy-Stephenson J. Mineral intakes of elderly adult supplement and non-supplement users in the Third National Health and Nutrition Examination Survey. J Nutr. 2002;132(11):3422-3427.

5. Dixon LB, Winkleby MA, Radimer KL. Dietary intake and serum nutrients differ between food-insufficient and food-sufficient families: Third National Health and Nutrition Examina­tion Survey, 1988-1994. J Nutr. 2001;131(4):1232-1246.

6. Institute of Medicine Food and Nutrition Board. Dietary Ref­erence Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vana­dium, and Zinc. Washington, DC: National Academies Press; 2001.

7. Dietary supplement fact sheet: zinc. National Institutes of Health Office of Dietary Supplements website. http://ods.od.nih.gov/factsheets/Zinc-HealthProfessional/#en9.

8. USDA national nutrient database for standard refer­ence. United States Department of Agriculture Agricultural Research Service website. http://www.ars.usda.gov/Services/docs.htm?docid=8964. Last modified October 9, 2012.