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Zinc, Covid and the elderly

December 16, 2020 - 14:21 -- Pierre Lutgen

LOW ZINC STATUS: A RISK FOR PNEUMONIA IN THE ELDERLY

Plasma Zn decrease is strongly related to age and may be a predictor of all-cause mortality in elderly population. In a study in Italy plasma zinc levels were measured in individuals having an age range of 10–93 years. No significant differences in plasma zinc concentrations were found between males and females. Up to the age of 50 years, the mean plasma zinc of normal individuals remained relatively constant at 70 ± 32µg/100 ml after which the levels decreased.

Chooi M.K. Todd J.K. · Boyd N.D. Influence of Age and Sex on Plasma Zinc Levels in Normal and Diabetic Individuals. Nutr Metab 1976;20:135–142
E Mocchegiani, Zinc and ageing: third Zincage conference. Immunity & Ageing 2007; 4: 5.
Malavolta M, Giacconi R, Piacenza F, et al. Plasma copper/zinc ratio: an inflammatory/nutritional biomarker as predictor of all-cause mortality in elderly population. Biogerontology. 2010;11(3):309-319.

Aged individuals are significantly more susceptible to zinc deficiency, increasing the likelihood of acquiring life threatening viral infections.

A J Cabrera,Zinc,aging,and immunosenecence : an overview. Pathology of Aging& Age Related Diseases, 2014.

In an observational study on 379 elderly patients it was found that in the low serum zinc group the incidence of pneumonia (no.per person-year) was 0.66 vs 0.25 in the high serum zinc group. The duration of pneumonia (days per person-year) was 6.82 vs. 3.19. The overall death toll (no. per person-year) was 0.19 vs. 0.12

Barnett JB, Hamer DH, Meydani SN. Low zinc status: a new risk factor for pneumonia in the elderly?. Nutr Rev. 2010;68(1):30-37.
Eugenio Mocchegiani, Zinc and ageing: third Zinc age conference Immunity & Ageing20074:5 DOI: 10.1186/1742-4933-4-5. 10.1016/j.redox.2014.06.01

ZINC AND THE IMMUNE SYSTEM

Zinc supplementation is associated with substantial reductions in the rates of diarrhea, malaria and pneumonia, three leading causes of death.

Brooks WA, Yunus M, Santosham M, Wahed MA, Nahar K, Yeasmin S, Black RE. Zinc for severe pneumonia in very young children: double-blind placebo-controlled trial. Lancet. 2004 May 22;363(9422):1683-8.
Bhutta ZA, Black RE, Brown KH, Shankar A. Prevention of diarrhea and pneumonia by zinc supplementation in children in developing countries: pooled analysis of randomized controlled trials. Zinc Investigators' Collaborative Group. J Pediatr. 1999 Dec;135(6):689-97

Zinc given as an adjunct to the treatment of severe pneumonia is effective in reducing the mortality of severe pneumonia.

Wang L, Song Y. Efficacy of zinc given as an adjunct to the treatment of severe pneumonia: A meta-analysis of randomized, double-blind and placebo-controlled trials. Clin Respir J. 2018 Mar;12(3):857-864.
Srinivasan MG, Ndeezi G, Mboijana CK, Zinc adjunct therapy reduces case fatality in severe childhood pneumonia: a randomized double blind placebo-controlled trial. BMC Med. 2012 Feb 8;10:14. doi: 10.1186/1741-7015-10-14. PMID: 22316073 Free PMC article. Clinical Trial.

In a study on virus replication, the inhibitory effect of zinc salts was concentration dependant and was not observed with other salts containing divalent cations such as calcium, magnesium and manganese.

Suara RO, Crowe JE Jr. Effect of zinc salts on respiratory syncytial virus replication. Antimicrob Agents Chemother. 2004;48(3):783-790.

But zinc is rather prophylactic than curative. Zinc supplementation given during the acute episode does not help in short term clinical recovery from severe pneumonia

Shah GS, Dutta AK, Shah D, Mishra OP. Role of zinc in severe pneumonia: a randomized double bind placebo controlled study. Ital J Pediatr. 2012 Aug 2;38:36.

Dietary factors influence zinc absorption. Phytate which is present in staple foods like cereals, corn and rice, has a strong negative effect on zinc absorption from composite meals. Iron can have a negative effect on zinc absorption. Amino acids, such as histidine and methionine are known to have a positive effect on zinc absorption. Saponins have no effect on zinc absorption from a single meal in the rat

S Southon, A. J. A. Wright, K. R. price, The effect of three types of saponin on iron and zinc absorption. British Journal of Nutrition (1988), 59, 389-396 389. AFRC Institute of Food Research, Norwich Laboratory, Colney Lane, Norwich NR4 7UA.

For pulmonary tuberculosis, a study from Mexico showed that earlier elimination of bacilli from sputum was associated with improved zinc status and Th1 immune response. If confirmed in clinical trials, this adjunctive therapy could be used to shorten the amount of time that TB patients are contagious. Some recent pilot clinical trials in Kivu and Tanzania have confirmed that Artemisia annua and afra infusions, a plant rich in in zinc, lead to a surprisingly fast recovery of TB patients with total absence of mycobacteria in sputum after a few weeks of treatment (Pascal Gisenya, personal communication)

Armijos RX1, Weigel MM, Chacon R, Flores L, Campos A. Adjunctive micronutrient supplementation for pulmonary tuberculosis. Salud Publica Mex. 2010 May-Jun;52(3):185-9.

Zinc has a pivotal role in the entire immune system fostering resistance to infections by virus, fungi, parasites and bacteria. Zinc functions as an antioxidant. It protects cells of damaging effects of oxygen radicals generated during immune activation. But the human body has no zinc storage system, hence, a daily nutritional zinc uptake is necessary. The immune system is strongly impaired by zinc deficiency, predominantly the cell-mediated response by T-lymphocytes. This leads to a reduced CD4 cell count and T-cell numbers, a decreased ratio of type 1 to type 2 T-helper cells with lower production of T-helper type 1 cytokines like interferon-gamma, and compromised T-cell mediated immune defense.

Hönscheid A, Rink L, Haase H. T-lymphocytes: a target for stimulatory and inhibitory effects of zinc ions. Endocr Metab Immune Disord Drug Targets. 2009 Jun;9(2):132-44. Review.

Approximately 300 enzymes require zinc for their activities. Zinc is an essential trace mineral for DNA synthesis, cell division, and protein synthesis, all necessary processes for tissue regeneration and repair. Zinc deficiency has been associated with poor wound healing and decreased breaking strength of animal wounds, which can result from decreased protein and collagen synthesis during healing found in zinc-deficient animals.

CONCLUSION

It is a shame that in this Covid crisis, zinc supplementation to elderly did not receive widespread promotion and was ignored by health authorities of most countries. Cui bono?

Zinc supplementation to maintain normal serum zinc concentrations in the elderly may help reduce the incidence of pneumonia and associated morbidity.

Barnett JB, Dao MC, Jacques PF, Schreiber R, Kong E, Meydani SN. Effect of zinc supplementation on serum zinc concentration and T cell proliferation in nursing home elderly, Am J Clin Nutr. 2016 Mar;103(3):942-51.

Meydani SN, Leka LS, Hamer DH. Serum zinc and pneumonia in nursing home elderly. Am J Clin Nutr. 2007 Oct;86(4):1167-73. doi: 10.1093/ajcn/86.4.1167. Erratum in: Am J Clin Nutr. 2008 Apr;87(4):1071

Major depression is a mood disorder that causes changes in physical activity, appetite, sleep and weight. A double-blind randomized clinical trial indicated that zinc supplementation contributes to the improvement of major depressive disorders.

Ranjbar E, Kasaei MS, Mohammad-Shirazi M, et al. Effects of zinc supplementation in patients with major depression: a randomized clinical trial. Iran J Psychiatry. 2013;8(2):73-79

Comments

Submitted by Pierre Lutgen on

A few readers of my blog "Zinc, Covid and the elderly" suggested a closer look at the effect of phytate and compost on zinc bioavailability, as zinc is an important antiviral element.

The addition of organic matter in soil can modify the bioavailability of metals. A greenhouse pot experiment was carried out using an edible plant species. In the compost treatments, plants showed the lowest Zn concentration in shoots. Indeed, Zn plant content and translocation to shoots seems to be affected. Compost amendments significantly reduced Zn content and translocation in comparison to other treatments.

Al Chami Z, Cavoski I, Mondelli D, Miano T. Effect of compost and manure amendments on zinc soil speciation, plant content, and translocation in an artificially contaminated soil. Environ Sci Pollut Res Int. 2013 Jul;2

The potential use of biochar (pyrolized biomass) from olive mill waste for in situ remediation of metal contaminated soils was evaluated. Biochar was mixed with metal contaminated soil originating from the vicinity of an old zinc smelter. Soil-biochar mixtures were equilibrated for 30 and 90 days. This olive mill waste reduced the bioavailability of metals.

Amine Hmid, Ziad Al Chami, Wouter Sillen, Alain De Vocht, Olive mill waste biochar: a promising soil amendment for metal immobilization in contaminated soils. Environ Sci Pollut Res Int. 2015 Jan;22(2):1444-56.

Compost at rates of 0, 15 and 30 ton ha−1 was used to examine its role in plant growth and heavy metals uptake. The high rate of compost (30 ton ha−1) decreased zinc (Zn) concentrations in the leaves of plants by 15.8 and 13.0%.

Mamdouh A. Eissa (2015) Impact of Compost on Metals Phytostabilization Potential of Two Halophytes Species, International Journal of Phytoremediation, 17:7, 662-668

Zinc distribution and speciation within different organs (root, petiole, and leaf) of the edible plant Eruca vesicaria L. Cavalieri were determined for plants grown in polluted soil with or without compost amendment. Major differences were observed within the plants. Plants grown in the presence of compost were able to partly block zinc immediately outside the root endodermis in the form of zinc-phytate.

Roberto Terzano, Ziad Al Chami, Bart Vekemans, Koen Janssens, Zinc Distribution and Speciation within Rocket Plants (Eruca vesicaria L. Cavalieri) Grown on a Polluted Soil Amended with Compost J. Agric. Food Chem. 2008, 56, 9, 3222–3231

Phytate in soil is probably the main reason of the low biovaliability of zinc to plants. Phytate is a storage compound in food that cannot be fully digested by many animal species, passes unabsorbed through the gastrointestinal tract, resulting in the accumulation of phytate in manures. It also can enter the soil directly from plants.

Amirabdollahian, F., & Ash, R. (2010). An estimate of phytate intake and molar ratio of phytate to zinc in the diet of the people in the United Kingdom. Public Health Nutrition, 13(9), 1380-1388,
Giles C.D., Cade-Menun B.J. (2014) Phytate in Animal Manure and Soils: Abundance, Cycling and Bioavailability. In: He Z., Zhang H. (eds) Applied Manure and Nutrient Chemistry for Sustainable Agriculture and Environment. Springer, Dordrecht

Submitted by Pierre Lutgen on

A recent paper confirms the beneficial effects of zinc administration during Covid-19 infections.

Eric Finzi, Allan Harrington, Zinc Treatment of outpatient COVID‐19: A retrospective review of 28 consecutive patients. Journal of Medical Virology 21 January 2021

A historical evaluation of seven randomized controlled trials had shown that zinc administration shortened the mean duration of the common cold by 33% .

The authors report results of clinical trials where laboratory confirmed COVID‐19 cases were started on zinc gluconate/citrate lozenges (23 mg of elemental zinc, 21 patients) or zinc acetate lozenges (15 mg of elemental zinc, 7 patients), at a total dosage of 2–2.5 mg/kg/day.

Ten symptoms were scored or assessed according to a COVID‐19 symptom checklist : Fever, shortness of breath, cough, nausea/vomiting, diarrhea, sore throat, headache, muscle/body aches, fatigue and loss of smell/taste.

All 28 patients were improved after 7 days of zinc administration. Symptomatic improvement began a mean of 1.6 days after zinc treatment and symptoms had almost completely disappeared on day 7. No patients were hospitalized after zinc treatment. Patients older than 40 began recovery slightly later than under 40. Zinc deficiency is often present in the elderly. However, the clinical outcome at 7 days was the same, and this is not the typical COVID‐19 course. It is generally accepted that in mild cases of COVID‐19 (i.e. without zinc treatment) about 80% of patients begin improving only after day 10; 20% worsen the second week.

The mechanisms by which zinc may help COVID‐19 patients are not fully understood, but include direct inhibition of viral replication, improvement of mucociliar clearance of SARS‐Cov‐2, reduction of secondary bacterial infection, improvement of lung and kidney tissue healing. Zinc supplementation reduces the incidence of pneumonia and improves diarrhea.