Zinc: A key ally in cystic fibrosis

The essential role of zinc in animals was first brought to light in the 1930s; however, it was only in 1961 that it was discovered that zinc was indispensable for human health after a zinc deficiency was observed in a human subject.¹ Since then, interest in this nutrient has increased dramatically.¹ But how important is zinc in terms of cystic fibrosis?

Risk of zinc deficiency among persons with cystic fibrosis

People with cystic fibrosis are at risk for zinc deficiency.² Despite zinc supplements that greatly exceed recommended doses,³ the prevalence of a zinc-deficient nutritional status can reach 40% among children with cystic fibrosis.⁴ Furthermore, low plasma zinc levels were reported in approximately 30% of infants with cystic fibrosis during neonatal screening.⁵ It should be noted that there is no data at the current time on the zinc status of adults with cystic fibrosis.

It is a well-known fact that pancreatic insufficiency, a condition that affects 85% of persons with cystic fibrosis, results in the maldigestion and malabsorption of lipids and fat-soluble vitamins (A, D, E and K), as well as significant steatorrhea (fat excreted in the stools).⁶ However, pancreatic insufficiency also causes the malabsorption of minerals, including zinc.⁷

Zinc is absorbed through the small intestine, primarily in the jejunum.⁸ Maintaining a normal zinc nutritional status depends on both the effective intestinal absorption of dietary zinc and the reabsorption of zinc in digestive secretions.¹ It has been suggested that infants with cystic fibrosis have lower rates of dietary zinc absorption and reduced zinc reabsorption in digestive secretions.⁵ However, these symptoms, which appear to be secondary to maldigestion, malabsorption and steatorrhea,⁵ only seem to be partially corrected through the use of pancreatic enzyme supplements, which are normally prescribed for cystic fibrosis patients with pancreatic insufficiency. This suggests that there are factors other than pancreatic insufficiency involved.⁴

Clinical manifestations of deficiency have also been reported in infants with cystic fibrosis.^9-10 Zinc deficiency can lead to clinical symptoms such as immune system disruptions, susceptibility to infection, reduced sense of taste and smell, a decline in growth, diarrhea and a loss of appetite.^11-12 However, these clinical manifestations lack specificity, and cystic fibrosis patients often present similar symptoms that may be entirely unrelated to their zinc status.¹¹ As a result, zinc deficiency cannot be diagnosed solely on the basis of the presence of these clinical signs. Hence, the measurement of plasma zinc levels is a key diagnostic parameter.

Specific features and functions of zinc

Zinc is a trace element, that is, a nutrient required in low concentrations to meet an organism’s needs. It is the second most abundant mineral in organisms after iron.¹¹ The body of an adult human contains about two grams of zinc,¹³ which is found mainly in cells.⁹ Over 85% is stored in the bones and muscles, whereas only 0.1% is found in the bloodstream.⁸ Serum or plasma zinc levels are not the ideal markers for assessing zinc nutritional status¹¹ since they decrease in the presence of an infection, trauma, stress or steroid use, or after a meal.^14-15 Nevertheless, this is the most commonly used method at the current time for determining the risk of zinc deficiency in the population.¹¹

Zinc is considered as a “type 2 nutrient,” which means it is required for general, non-specific metabolic functions.¹⁴ It plays a role in many enzymatic reactions, in protein synthesis and in the growth process,¹ which is why this trace element has been particularly studied among children with cystic fibrosis, who are known to present sub-optimal growth. Zinc plays an active role in the maintenance of the immune system, acts as an anti-inflammatory agent, and helps maintain the defence system against oxidative stress.¹⁵ People with cystic fibrosis present repetitive infections, chronic inflammation and a high level of oxidative stress.

Where do we get zinc?

Zinc is present in many kinds of food, such as meat, some types of seafood, legumes, nuts, whole-grain cereals, certain enriched breakfast cereals and milk products.^8-16 Oysters are the best source of zinc naturally present in food.¹⁶ Zinc found in animal source foods is better absorbed by the body than zinc in plant-based foods.¹ This can be explained by the fact that plants contain phytates, which chelate (bind to) zinc in the small intestine and reduce its absorption.¹

Dietary Sources of Zinc¹⁶

Food	Quantity	Zinc Content (mg)
Farmed oysters (eastern US), cooked	75 g	33.86
Lean ground beef (cooked)	75 g	5.38
Chicken, dark meat (boiled)	75 g	2.34
Canned chickpeas	175 ml	1.88
Raw wheat germ	30 ml	1.79
Grilled almonds	60 ml	1.72
Cheddar cheese	50 g	1.56

Since zinc is an essential nutrient, it comes as no surprise that it is included, in varying concentrations, in a number of vitamin and mineral supplements. In the case of cystic fibrosis, the so-called “specialized” multivitamin and mineral supplements are made up primarily of fat-soluble vitamins (A, D, E and K), which are affected by malabsorption. The usual dosage is two tablets a day. As an example, one AquADEKs® tablet and one SourceCF^® tablet contain 5 mg¹⁷  and 15 mg¹⁸ of zinc, respectively. The zinc content of  multivitamin/mineral supplements designed for the general public—and sometimes used for cystic fibrosis patients—such as Centrum Forte^®, is by no means insignificant: each tablet contains 7.5 mg of zinc.¹⁹

Adult dietary zinc requirements

Since the exact prevalence of zinc deficiency is not yet known, the Cystic Fibrosis Foundation has not issued any specific recommendations regarding daily zinc intake for people with cystic fibrosis.²⁰ In the general public aged 18 and over, the daily recommended dose is 11 mg for men and 8 mg for women; however, daily requirements for persons with cystic fibrosis may be higher²⁰ because they have reduced absorption and their bodies may use more zinc as a result of certain complications relating to cystic fibrosis.

At the current time, there is no consensus regarding the need to regularly measure zinc levels in cystic fibrosis patients or give them zinc supplements.⁴ Zinc supplements are only recommended for patients with persistent steatorrhea and for those who are failing to gain weight despite the fact that they are taking pancreatic enzyme supplements.⁴ In order to shed light on the need to measure zinc levels and prescribe supplements, the team at the Clinic for Adults with Cystic Fibrosis at the University of Montréal Hospital Centre (CHUM) has, since 2009, been measuring plasma zinc levels in all its patients on an annual basis. It was discovered that a number of patients had low zinc levels (the findings will be published by the authors at a later date). The supplementation protocol was established as follows: if the plasma level is lower than the reference level (9.2 µmol per litre), one 50 mg zinc gluconate tablet per day is prescribed for three months. This is usually sufficient to normalize the serum level, which is checked by means of a blood test at the end of the three months; if not, the supplement is prescribed for another three months.

Zinc’s role in various complications associated with cystic fibrosis

-Zinc and vitamin A

Zinc influences many aspects of vitamin A nutritional status (absorption, metabolism, transport and utilization),²¹ which is generally compromised in cystic fibrosis patients because of malabsorption. Zinc is necessary for hepatic synthesis of retinol‑binding protein (RBP).¹ RBP is a protein synthesized by the liver which transports vitamin A from the liver to target tissues.²² Zinc is required to mobilize vitamin A and RBP from the liver into the bloodstream.¹

Zinc deficiency can reduce RBP synthesis in the liver, which leads to lower plasma RBP levels.²¹ Furthermore, zinc deficiency is commonly associated with lower plasma vitamin A levels, even in the presence of normal hepatic vitamin A reserves.²³ Since people who have cystic fibrosis are likely to have a nutritional status that is deficient in vitamin A, it is hard to tell whether this is a result of malabsorption or whether it is a secondary effect of an underlying zinc deficiency. Measuring plasma zinc, therefore, may prove to be a key distinguishing tool.

-Zinc and lung function

Particular emphasis has been given to the importance of zinc in the respiratory system.¹⁵ Zinc is an integral part of the structure and function of many of the enzymes involved in pulmonary function.⁷ In a group of children with cystic fibrosis, it was observed that low serum zinc concentrations were associated with decreased forced vital capacity.¹¹

Similarly, lung function is frequently impaired in persons with cystic fibrosis in the presence of inflammation.¹¹ In addition, an inflammatory state is known to reduce plasma zinc levels.¹¹ Given that one of the functions of zinc is to maintain the immune system, a decline in plasma zinc levels in individuals with reduced lung function could aggravate infections and inflammation, thus creating a vicious circle.¹¹

Studies have shown that taking zinc supplements reduces lung infections among various population groups.^26-27 However, very little research has been done on the effectiveness of zinc supplements for people with cystic fibrosis.⁷ Hence, the relationship between plasma zinc and pulmonary function, as it relates to cystic fibrosis, merits further investigation.¹¹

-Zinc and bone metabolism

The increased life expectancy of people with cystic fibrosis has contributed to the emergence of numerous complications, including osteopenia and osteoporosis.²⁶ According to a recent meta-analysis, the prevalence of osteoporosis and osteopenia is estimated to be approximately 23.5% and 38%, respectively, among adults with cystic fibrosis.²⁶

It has been suggested that zinc is a key mineral in bone metabolism.²⁷ It stimulates bone formation and mineralization and prevents bone degradation.²⁸ Zinc deficiency has been identified as a risk factor for osteoporosis.¹² To date, there have been no studies on the link between the zinc nutritional status of people with cystic fibrosis and bone complications. However, dietary zinc intake could help prevent osteoporosis by increasing bone mass.²⁸

-Zinc and diabetes

Diabetes is a cystic fibrosis–related complication that generally appears in young adults in their early twenties.²⁹ The prevalence of cystic fibrosis–related diabetes increases with age and can exceed 40% after age 30.³⁰ Likewise, glucose intolerance is a condition frequently associated with cystic fibrosis.³⁰

Zinc is involved in carbohydrate metabolism,³¹ as well as in the synthesis of insulin,^31-32 the hormone secreted by the pancreas to regulate blood sugar levels. According to the literature, low plasma zinc levels are associated with an increased prevalence of diabetes in the general public.³³ It has also been reported that there is a correlation between zinc deficiency and high blood sugar.³²

Oxidative stress also contributes to the development and progression of diabetes and related complications.³¹ Zinc makes up part of the structure of a number of antioxidant enzymes that help combat free radicals,³¹ which are unstable molecules that can cause oxidative damage. Zinc deficiency, therefore, appears to lead to increased oxidative stress.³¹ Although no studies have been conducted on the link between diabetes and zinc in persons with cystic fibrosis, this mineral is thought to prevent the development of diabetes by reducing blood sugar levels, influencing the secretion and/or action of insulin and reducing oxidative stress.³²

-Zinc and liver disease

Approximately one third of cystic fibrosis patients have impaired liver function.³⁴ The liver contains about 1.8% of the body’s zinc³⁵ and plays a key role in regulating the zinc nutritional status.¹² Conversely, the liver needs zinc to be able to function effectively.¹² Hence, liver diseases affect the organism’s zinc levels, while zinc deficiency could play a role in the development of liver ailments.¹²

Studies have shown that individuals with chronic liver disease or cirrhosis have lower serum and hepatic zinc levels compared with healthy subjects.¹² Furthermore, other studies have found that the decrease in plasma zinc is inversely proportional to the degree of liver damage,¹² in other words, the greater the seriousness of the liver disease, the greater the reduction in plasma zinc concentrations. Although no similar research has been conducted among cystic fibrosis patients, this trace element could offer protection against liver dysfunction.¹²

Conclusion

In general, our knowledge about the importance of zinc in regulating a number of systems has increased considerably in recent years. Zinc is, without a doubt, a nutrient that should not be overlooked and one that is essential to maintaining good health.

As concerns cystic fibrosis, even though a number of studies have examined the zinc nutritional status of infants and children who have this disease, there is no data in the literature on the zinc nutritional status of adults with cystic fibrosis and on its association with certain clinical parameters of interest. It is quite possible that the zinc nutritional status among adults may also be compromised.

Furthermore, studies conducted among population groups that do not have cystic fibrosis have shown that zinc can be beneficial in the case of certain pathological conditions, such as diabetes, osteoporosis and impaired liver function, which are more prevalent among adults with cystic fibrosis. As a result, more research is needed to understand the role played by zinc in persons with cystic fibrosis of all ages with respect to some of the complications associated with cystic fibrosis.

In the absence of specific guidelines or recommendations concerning recommended intake, supplements and the dose of zinc required to obtain optimal serum levels in people with cystic fibrosis, overall nutritional care remains a key factor in improving the health of people with cystic fibrosis.

 

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