Zinc supplementation and reduction of inflammation

Juana Zargon N01178080

Introduction:

Zinc is a metal found in all cells of the body, therefore in all organs, tissues, and bodily fluids. It

is consumed in the diet, as well as produced endogenously. Dietary sources are mainly animal proteins,

such as beef, eggs, and cheese. Zinc’s absorption tends to increase with protein intake, therefore the

intake of animal proteins may improve the bioavailability of zinc from plant food sources. Endogenously,

zinc is created by pancreatic and biliary secretions, which work to regulate zinc homeostasis. Its role can

be characterized into catalytic, structural, and regulatory functions.1 When zinc is consumed, it must first

be absorbed in the small intestine by carrier-mediated mechanisms. Absorption is concentration

dependent and may be influenced by zinc status. Low zinc status increases efficiency of absorption, while

high zinc status shows a reduced efficiency.1 The expression and cellular distribution of zinc transporters

is regulated by changes in zinc status. Both Znt and zip transporters show unique tissue-specific

expression, different responses to zinc status in the body, and different responses to stimuli from

hormones and cytokines.1 The average requirement of zinc needed is estimated by the amount of zinc that

must be absorbed to offset the amount lost through intestinal and non-intestinal pathways. Zinc

requirements increase during growth, pregnancy, and lactation. The recommended daily amount of zinc

for women is 8 mg, while 11 mg for men. With zinc deficiency, growth and development may be stunted

and the risk of infection increases. Dermatitis, poor wound healing, alopecia, and skeletal abnormalities

may also occur.1 The purpose of this paper is to determine whether zinc supplementation aids in reducing

inflammation in the body.

Methods:

The primary databases used for research were Pubmed and Science Direct. In order to gather data

from these databases, the search terms “zinc supplementation, zinc and inflammation, zinc and intestines,

zinc and pulmonary, zinc and respiratory infection, zinc and asthma, and zinc and cardiovascular” were

used. The study designs of the research papers used were randomized controlled trials, with the exception

of one integrative review article on zinc and its importance for human health. The methods used were not
only to provide a brief statement as to the importance of zinc, but also to eventually determine zinc

supplementation’s ability in reducing inflammation.

Main Findings:

Intestinal

The intestinal tract plays an important role in preventing exogenous antigens, such as

microorganisms and their toxins, from entering the intestinal mucosa and the systemic circulation. An

intact intestinal barrier is necessary in the maintenance of health and the prevention of tissue injury and

several diseases. A study conducted by Jiao L et al,2 explored the effects that copper and zinc loaded

montmorillonite would have on intestinal integrity, the expression of genes associated with inflammation,

as well as TLR4-MyD88 and TGF-beta 1 signaling pathways in weaned pigs after being exposed to LPS.

The impaired intestinal epithelial barrier is caused by the inflammatory response and the overproduction

of inflammatory cytokines. This study influenced by others which have shown that high doses of zinc and

copper may increase resistance to inflammation and barrier dysfunction. The study hoped to reveal

whether supplemental Cu/Zn-Mt could improve intestinal epithelial barrier by regulating the expression

of genes associated with inflammation in weaned pigs after being exposed to E. Coli LPS. In the study, 18

barrows, or male pigs castrated before puberty, were randomly assigned to 3 groups consisting of 6 each.

After 21 days of feeding, the pigs were injected with E. Coli. The LPS groups were fed a basal, while the

LPS + Cu/Zn-Mt group received the same diet with an addition of 2 g/kg of Cu/Zn-Mt. The

concentrations of copper and zinc, respectively, were 1.89 x 10^4 mg/kg and 3.72 x 10^4 mg/kg. The

study showed that the dietary supplementation alleviated the barrier function disorder caused by E. Coli

LPS. The observations were supported by their previous study that dietary supplementation of Cu/Zn-Mt

supported epithelial barrier integrity by decreasing plasma diamine oxidase activities and increasing the

protein expression of tight junctions. It has been suggested that the protective barrier effect of Cu/Zn-Mt

may be explained by the interactions of all components, therefore the interactions between copper, zinc,
and montmorillonites. The supplementation resulted in decreased pro-inflammatory cytokine expression,

indicating that LPS-induced inflammation was minimized by the intervention.

Pulmonary

Different studies have suggested the importance of trace elements and their role in inflammatory

processes, such as asthma. Zinc levels have shown to be low in the serum, hair, and sputum of patients

with asthma. In a study by Ghaffari J et al,3 the effects of zinc supplementation in children with asthma

were experimented. Trace elements such as selenium and zinc are essential in inhibiting the production of

free radicals thought to aggravate asthma through antioxidant enzymes. The consumption of zinc-

containing foods during pregnancy has been sown to be associated with a decreased risk of asthma in the

child. The aim of the study was to examine the effect of zinc supplementation on clinical symptoms as

well as pulmonary function tests in zinc-deficient children (<70 micrograms/dL) with moderate asthma.

The children were separated into the control (placebo) group or the supplement group (50mg/day.) After 8

weeks, there was a significant beneficial effect on both clinical symptom and lung function in bronchial

asthmatic patients. There was not a significant difference in total serum IgE levels between the control

and supplement group, which could be understood as changes in serum levels may not be an important

factor in bronchial asthma. This could be due to the anti-inflammatory effect by the inhibition of the NF-

kB pathway, leading to a decrease in serum IgE levels.

Cardiac

Metabolic syndrome is characterized by hyperglycemia, atherogenic dyslipidemia, elevated blood

pressure and abdominal obesity. These characteristics are associated with an increased risk of

cardiovascular disease and all-cause mortality. In a study conducted by Kim H et al,4 the effects of zinc,

magnesium, and chromium supplementation were tested on cardiometabolic risk in adults with metabolic

syndrome. Obesity is a long-term inflammatory state with altered adipokine production and increased

values of inflammatory cytokines. As zinc decreases inflammation, it is limiting the initiation and

progression of insulin resistance and diabetes. The case group was given 300 mg of magnesium, 600

micrograms of chromium, and 36 mg of zinc per day over a 24-week period, while the control group was
given a placebo. Although there was no significant difference in any of the metabolic risk factors, the

supplementation caused decreased serum CRP (inflammatory marker) levels relative to those in the

control group. The limitation of this study was the small sample size and lack of subject selection

considering the severity of insulin resistance and glucose intolerance along with the body mineral status.

Overall, the supplementation showed a decrease in inflammation.

A separate study by Wang S et al5 conducted on mice explored a similar idea of zinc

supplementation attenuating cardiac hypertrophy in obese mice. Obesity related hypertrophy is associated

with increased cardiac inflammation and P38 MAPK activation. The mice were fed either a high fat diet

or a normal diet containing one of three different zinc quantities: deficiency (ZD, 10 mg zinc per 4057

kcal), normal (ZN, 30 mg zinc per 4057 kcal) or supplement (ZS, 90 mg zinc per 4057 kcal). The findings

demonstrated that while a deficiency heightens cardiac hypertrophy, zinc supplementation alleviates it

through suppressing p38 MAPK-dependent cardiac inflammatory and hypertrophic pathways, leading to

the prevention of obesity related hypertrophy. Zinc supplementation mildly attenuated the high fat diet-

induced insulin resistance, hyperinsulinemia, and hypertriglyceridemia, showing promise in using zinc

supplementation as a treatment option in metabolic syndrome.

Discussion and Conclusion:

The purpose of this paper was to analyze the effects of zinc supplementation on inflammation.

The data was organized by intestinal, pulmonary, and cardiac inflammation. Based on the data collected,

it seems that zinc supplementation can aid in reducing inflammation throughout the body. Whether

intestinal, pulmonary, or cardiac, zinc supplementation showed to be beneficial in inhibiting certain

pathways responsible for the activation of inflammatory response. More research is needed to ensure of

the conclusion reached, since many of the studies were either not on human subjects, had considerable

limitations such as sample size or lack of specific tests which would be more accurate in the data

collection process, or were conducted with simultaneous supplementations in addition to zinc. No studies

were found stating that zinc supplementation is not beneficial in reducing inflammation but this does not
mean supplementation is guaranteed to alleviate an individual from a certain illness or disorder. In order

to gather better and more reliable information, further investigation should be conducted on the effects of

zinc supplementation alone on a large sample size of human subjects over long-term periods.

References:

1. Roohani N, Hurrell R, Kelishadi R, Schulin R. Zinc and its importance for human health: An
integrative review. J Res Med Sci. 2013;18(2):144–157.
2. Jiao L, Wang CC, Wu H, et al. Copper/zinc-loaded montmorillonite influences intestinal
integrity, the expression of genes associated with inflammation, TLR4-MyD88 and TGF-β1
signaling pathways in weaned pigs after LPS challenge. Innate Immun. 2017;23(8):648-655. doi:
10.1177/1753425917733033.
3. Ghaffari J, Khalilian A, Salehifar E, Khorasani E, Rezaii MS. Effect of zinc supplementation in
children with asthma: A randomized, placebo-controlled trial in northern islamic republic of
iran. Eastern Mediterranean Health Journal. 2014;20(6):391-396
4. Kim H, Kim S, Eun Y, Song S. Effects of zinc, magnesium, and chromium supplementation on
cardiometabolic risk in adults with metabolic syndrome: A double-blind, placebo-controlled
randomised trial. J Trace Elem Med Biol. 2018;48:166-171. doi: 10.1016/j.jtemb.2018.03.022.
5. Wang S, Luo M, Zhang Z, et al. Zinc deficiency exacerbates while zinc supplement attenuates
cardiac hypertrophy in high-fat diet-induced obese mice through modulating p38 MAPK-
dependent signaling. Toxicol Lett. 2016;258:134-. doi: 10.1016/j.toxlet.2016.06.020