Zinc is an important trace element. It plays a variety of indispensable roles in the human body, widely involved in protein, lipid, nucleic acid metabolism and gene transcription processes.
Due to the importance of zinc to men’s health (it is regarded as a nutrient related to impotence), if the lack of it will seriously affect fertility, it is also called sex mineral.
What are the benefits of zinc intake in empirical medicine? Are there any side effects or contraindications? See text analysis for details.
What is Zinc?
Zinc is the second most important metabolic essential micronutrient in the human body after iron. It is an important catalysis (related to more than 100 enzymes), structure and regulation ion, which participates in homeostasis, immune response, cell signal transmission, oxidative stress, Physiological processes such as apoptosis and aging.
Zinc is involved in DNA synthesis, RNA transcription, cell division and activation, and prevention of cell apoptosis. In addition to the subtle differences in molecular functions, it is also necessary for sperm production, embryo and fetal growth.
Human tissues contain about 2 to 3 grams of zinc, and nearly 90% is found in muscles and bones. Other organs containing high concentrations of zinc include prostate, liver, gastrointestinal tract, kidney, skin, lung, brain, heart and pancreas.
What happens to zinc deficiency? What are the symptoms?
Normal zinc levels in adults range from 70 to 250 ug/dl, mild deficiency occurs when values drop to 50 to 60 ug/dl, and severe deficiency occurs when zinc levels < 50 ug/dL.
The clinical appearance of zinc deficiency is nonspecific and can be broadly divided into the following categories based on differences in zinc levels.
Symptoms of mild to moderate deficiency (zinc level 50 to 60 ug/dL) may include:
Anorexia, glossitis, nail dystrophy, decreased immunity, infection, change of taste, loss of taste, weight loss, developmental delay, delayed puberty, rough skin, mental malaise, delayed wound healing, dark adaptation abnormalities, oligospermia, hyperammonemia…
Symptoms of severe deficiency (zinc level < 50 ug/dL) may include:
Hypogonadism (men), diarrhea, alopecia, bullous pustular dermatitis, brain dysfunction, impaired night vision, mood disorders, infections, drowsiness…
The overall global prevalence of zinc deficiency is expected to exceed 20%, and in developing countries it could affect more than 2 billion people.
This ubiquitous occurrence, accompanied by the diversity of clinical manifestations, makes zinc deficiency a serious nutritional problem with significant impact on human health.
Blood tests for zinc are usually inaccurate because most zinc is accumulated inside cells and is not free in the blood.
Who are the groups prone to zinc deficiency?
- Suffer from inflammatory gastrointestinal diseases (such as ulcerative enteritis)
- Pregnant and lactating women
- Suffer from chronic kidney disease
- Malnutrition, including suffering from anorexia or bulimia
- Sickle cell anemia
- Genetic variation
- Extensive burns
- Suffer from chronic debilitating diseases
- Drug use, such as penicillamine and diuretics
- Enteropathic acral dermatitis
What are the proven benefits of zinc supplementation?
Zinc is beneficial for immune function
Humans live in a world of large numbers of microorganisms that contain toxic or allergenic substances that threaten normal homeostasis, so the immune system uses a complex set of protective mechanisms (immune responses) to control and generally eliminate these organisms and toxins.
The innate response is the first line of defense against foreign substances, and these natural mechanisms include the skin barrier, saliva, tears, various cytokines, complement proteins, lysozyme, flora, and numerous cells, including neutrophils, basophils, eosinophils, monocytes, macrophages, the reticuloendothelial system, natural killer cells (NK cells), epithelial cells, endothelial cells, red blood cells, and platelets.
Adaptive response is the ability to use specific lymphocytes and their products (immunoglobulins and cytokines) to respond to invading microorganisms.
A systematic literature review and meta-analysis (35 randomized controlled trials, 1995 participants) noted that zinc supplementation (sulfate, gluconate, acetate, and glycine forms at doses ranging from 5 to 44 mg per day for 1.5 to 72 weeks) significantly reduced CRP, hs-CRP, neutrophils, TNF-α, and IL-6 and increased T cell markers CD3 and CD4 compared with controls. Note 1
In addition, subgroup analysis showed that the effect was particularly effective in participants who were zinc deficient or in a disease state.
*Conclusion: Zinc supplementation can help improve some innate and adaptive immune markers and have a positive effect on immune function, but limited by heterogeneity between studies, more research is needed to determine which groups of people can benefit from supplementation, as well as dosage, duration… and other questions
Zinc is beneficial attention deficit hyperactivity disorder
Attention deficit hyperactivity disorder, also known as attention-deficit hyperactivity disorder, is a common neurodevelopmental disorder in which genetic polymorphisms of dopamine receptors and dopamine transporters play an important role. The global prevalence is estimated at 7.2%.
In recent years, the potential influence of environmental (non-genetic) factors in the etiology of ADHD has attracted attention and may be preventable targets of the disease, such as nutritional factors, including deficiencies in certain micronutrients, which are increasingly recognized as possible risk factors.
A systematic literature review and meta-analysis (6 randomized controlled trials of 489 school-age children diagnosed with ADHD) noted that Compared with the control group, zinc supplementation had a significant positive effect on ADHD total scores, especially in combination with methylphenidate, but had no significant effect on hyperactivity scores and inattention scores. Note 1
*Conclusion: Zinc may provide positive help for ADHD in children, but limited by insufficient sample size and potential interfering factors, well-designed large-scale randomized controlled trials are still needed for further validation
Zinc is beneficial for depression
Melancholia (depression) is the most common mental illness and the leading cause of disability worldwide, with about 7 to 9 percent of adults in the United States experiencing major depressive disorder each year, and an estimated 8 million people meeting the criteria for major depression.
Some evidence suggests that depression is a multifactorial disorder. Genetics, aging, sedentary behavior, and many other factors contribute to the development of human depression, with only indirect workplace costs, characterized by low productivity and increased absenteeism, accounting for more than 60% of the total economic burden of depression and twice the direct medical costs.
A systematic literature review and meta-analysis (including five randomized controlled trials) suggested that zinc supplementation (duration from 10 to 12 weeks, doses ranging from 7 mg to 25 mg) was helpful in significantly reducing symptoms of depression in patients with a clinical diagnosis of severe depression and receiving antidepressant drugs. Note 1
In addition, subgroup analysis found that the antidepressant effect associated with zinc supplementation was particularly significant in subjects with an average age greater than or equal to 40 years.
The mechanism behind it may be related to zinc’s inhibitory effect on glutamate receptor NMDA, regulation of excitatory amino acids and inhibitory neurotransmission.
*Conclusion: Zinc supplementation may have a positive effect on improving depressive symptoms in patients with a clinical diagnosis of severe depression and receiving medication, but further validation is required due to the high risk of bias and high heterogeneity of the studies.
Zinc has anti-inflammatory effect
Inflammation is a normal defense mechanism that protects individuals from infection and other injuries, initiates the process of destroying pathogens and tissue repair, and restores balance to the infected or damaged area.
Inflammation is typically characterized by redness, swelling, warmth, pain, and loss of function, and involves interactions between multiple cell types that produce and respond to a number of chemical mediators.
A systematic literature review and meta-analysis (21 randomized controlled trials, 1321 participants) showed that zinc supplementation significantly reduced serum C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), and slightly reduced serum interleukin 6 (interleukin 6) compared with controls. Note 1
The underlying mechanism may be related to zinc’s regulation of peroxisome proliferators initiating receptors (PPAR-α), A20 protein signaling pathways, and immune cells.
*Conclusion: Zinc supplementation may have a positive effect on reducing inflammatory markers, but due to heterogeneity between studies, more large trials are needed to confirm the effective dose and duration period
Zinc is beneficial for acne (pimples) treatment
Acne (Acne vulgaris, also known as pimples) is acne, pimples, pustules, nodules, or cysts formed due to blockage and inflammation of the sebaceous glands of the hair follicles, and is a chronic inflammatory disease of the sebaceous glands that usually occurs during puberty but is also observed in adults (its lifetime prevalence is about 85%).
In an epidemiological study, 8.8% of acne patients were depressed, and women were twice as likely to be depressed as men, and genetics, diet, including chocolate and dairy consumption, and environmental factors were among the causes of acne.
A systematic literature review and meta-analysis (12 randomized controlled trials and 13 prospective observational studies with 2445 participants) noted a significant reduction in serum zinc levels in acne patients compared with controls, while zinc-treated patients had a significant improvement in mean inflammatory papules compared with those who did not receive zinc. Note 1
*Conclusion: Zinc (oral or topical) as monotherapy or as an adjunct may have a positive effect on acne improvement
Zinc is beneficial for childhood pneumonia
Pneumonia is an acute inflammation of the lower respiratory tract caused by microbial pathogens and is the main single cause of death in children under 5 years of age.
Bacterial infections are usually the main cause, but occasionally, viral respiratory infections such as influenza can increase the risk of subsequent bacterial pneumonia
Symptoms of pneumonia may be nonspecific and include: chest or abdominal pain, acute fever, cough, dyspnea, poor feeding or vomiting, and lack of interest in normal activities, especially in infants and younger children.
A meta-analysis (6 randomized, double-blind, placebo-controlled trials of 2216 children with severe pneumonia) noted that zinc as an adjunct to severe pneumonia reduced associated mortality, but did not significantly improve treatment failure and changes in antibiotic therapy. Note 1
*Conclusion: Zinc as an adjunct to the treatment of severe pneumonia in children may reduce mortality, but the small sample size is limited, and more studies are needed to support it
Zinc is beneficial for blood sugar control
Diabetes mellitus is a group of chronic metabolic disorders characterized by elevated blood sugar levels due to the body’s inability to produce insulin or resistance to insulin action, or both.
The prevalence of diabetes and prediabetes is increasing globally due to population growth, ageing, urbanization, unhealthy eating habits, obesity and lack of physical activity.
A systematic literature review and meta-analysis (32 randomized placebo-controlled trials involving 1700 participants in diabetes and high-risk diabetes groups) noted that participants supplemented with zinc supplementation had statistically significant reductions in fasting blood glucose, 2-hour postprandial blood glucose, fasting insulin, assessment of insulin resistance homeostasis models, glycated hemoglobin, and high-sensitivity C-reactive protein concentrations. Note 1
In addition, subgroup analyses showed that the effect of fasting blood glucose lowering was most significant in patients with diabetes and the use of inorganic zinc supplements.
The mechanism behind it is related to zinc’s ability to improve interactions between insulin receptors, increase glucose processing rates, and improve glucose tolerance.
*Conclusion: Zinc supplementation is a positive help in the prevention or adjuvant treatment of diabetes (especially in people with diabetes), but more large studies are needed to support this
Zinc is beneficial for blood pressure regulation
Hypertension is a major risk factor for cardiovascular events and death, with 69% of first myocardial infarction, 77% of first strokes, 74% of heart failure, and 60% of peripheral arterial disease associated with hypertension.
The diagnosis of hypertension is mainly a systolic blood pressure of 140 mm Hg or higher, or a diastolic blood pressure of 90 mm Hg or higher, affecting about 29% of American adults, and 22% of people with hypertension are unaware of their disease.
A systematic literature review and meta-analysis (9 randomized controlled trials with 544 participants) noted that zinc supplementation significantly reduced systolic blood pressure, but had no significant effect on diastolic blood pressure. Note 2
In addition, no nonlinear association was found between supplement dose and timing and changes in blood pressure.
The mechanism behind it is related to zinc’s contribution to nitric oxide synthase activity, enhanced peroxide clearance activity, and the manufacture of angiotensin-converting enzyme and neutral endopeptidase.
*Conclusion: Zinc supplementation may be helpful in blood pressure regulation, but more large, high-quality trials are needed to further validate the results
Zinc is beneficial for weight regulation
Long-term weight management is extremely challenging due to the interaction between biological characteristics, behavior, and the fattening environment.
Obesity is an important health problem because it predisposes people to a variety of comorbid conditions, including high blood pressure, dyslipidemia, coronary heart disease, type 2 diabetes, stroke, cancer and osteoarthritis, shortening life expectancy while reducing quality of life.
A meta-analysis (28 observational studies) found that serum zinc levels were significantly lower in obese children and adults. Note 1
A meta-analysis (27 RCTs with 1438 participants) noted that zinc supplementation had no significant effect on any weight-related outcomes in the overall analysis. Note 2
However, subgroup analysis showed that zinc supplementation increased the weight of hemodialysis patients and reduced the weight of otherwise healthy individuals who were overweight/obese but otherwise healthy.
*Conclusion: Zinc deficiency is associated with obesity, and zinc supplementation may have the effect of regulating weight in specific ethnic groups
Zinc is beneficial for male infertility
Infertility is a common clinical problem. Between 13% and 15% of couples worldwide are affected by infertility, and about 50% of the causes can be attributed to male factors.
Male factor infertility is characterized by abnormal semen analysis, such as low or missing sperm count, low sperm motility, and any drug, tobacco, alcohol, or illicit drug use.
After the age of 40, DNA damage in male sperm increases significantly, and sperm motility and viability decrease.
A systematic literature review and meta-analysis (20 studies involving 2600 infertile men and 867 normal controls) showed that the zinc content of seminal plasma in infertile men was significantly lower than in normal men. Additional zinc supplementation significantly increased semen volume, sperm motility, and percentage of normal sperm morphology in infertile men. Note 1
*Conclusion: Zinc supplementation may have a positive effect on male fertility, but limited by small sample sizes, more studies are needed to support this
Zinc can improve measles
Measles, an infection of the respiratory system, immune system and skin caused by the measles virus, is a highly contagious and vaccine-preventable disease.
Despite the availability of safe and effective vaccines, measles remains the leading cause of morbidity and mortality worldwide, especially in young children, with associated complications including pneumonia and encephalitis.
The disease is characterized by high fever (usually >40°C), Koch spots (spots in the mouth, usually 2-3 days before the rash for 3-5 days), malaise, loss of appetite, red eyes, runny nose, lethargy, and symptoms usually appear 7 to 14 days after exposure to the virus.
A Cochrane Database of Systematic Reviews (including one double-blind randomized controlled trial) found that oral zinc was not significantly helpful compared with placebo in resolving fever and shortness of breath, in time required to resolve fever and shortness of breath, restore appetite, and achieve a state of “greatly improved” or “cured”. Note 3
*Conclusion: There is insufficient evidence to confirm or refute the effect of zinc supplementation on measles in children due to the low quality of the available evidence.
Zinc strengthens immunity and accelerates cold recovery
Colds are the most common self-limiting viral infections in the world, and the main symptoms are sneezing, nasal congestion, sore throat, cough, hoarseness, headache, fever and muscle pain
Most of the existing cold treatment methods focus on alleviating symptoms, but they do not substantially help fight the virus that causes colds
Clinically, zinc is very important for the sound development of immune cells, if zinc deficiency will easily cause abnormal immune function and easy to cause infection, and the potential anti-cold mechanism of zinc (listed below). Note 4
- Increase the production of antiviral interferon
- Prevent the virus from attaching to the respiratory tract
- Anti-virus propagation
- Inhibit histamine and inflammatory hormone release
A meta-analysis (3 randomized, double-blind trials with 199 participants) showed that zinc lozenges (doses between 80–92 mg per day) helped to improve cold recovery by 3.1 times and cure rates 2.6 times higher than placebo (especially within 24 hours of onset of cold symptoms). Note 5
*Conclusion: Zinc lozenges may speed up recovery by taking zinc lozenges at the beginning of a cold, but the optimal dosage form and frequency of use still need more research to confirm
Zinc reduces the risk of gastrointestinal tract cancer
The gastrointestinal tract is a term used to define a series of tubular structures and appendages, which are involved in the process of digestion and absorption of food, and remove residual waste materials.
Any part of the gastrointestinal tract may be affected by malignant tumors, the highest incidence is the esophagus, stomach and colon.
A literature review and meta-analysis (19 studies with about 400,000 participants) pointed out that compared with the population with the lowest zinc intake, subjects with the highest intake of zinc reduced the risk of gastrointestinal cancer by 18%, especially colorectal cancer. Note 6
Subcohort analysis also found a significant association between zinc intake and gastrointestinal cancer risk in Asia, but no association was found in the United States and Europe.
*Conclusion: Zinc intake is inversely correlated with the risk of gastrointestinal cancer, especially colorectal cancer
Zinc reduces postoperative sore throat
Postoperative sore throat is mainly caused by endotracheal intubation during surgery, and is one of the most commonly complained postoperative adverse reactions by patients, with an incidence of about 30% to 70%, and the causes are often related to age, sex, smoking, operating technique, tube diameter, duration, catheter sleeve design and intraoperative tube movement. Note 7
A randomized, double-blind, placebo-controlled study of 79 patients undergoing endotracheal intubation surgery found that oral zinc lozenges (40 mg 30 minutes before surgery) reduced the incidence and severity of postoperative sore throat.
*Conclusion: Preoperative oral zinc ingots can reduce the pain events caused by surgical throat intubation, but it is limited by the small sample size and needs to be verified by more large-scale experiments
Zinc can improve blood lipid regulation
Dyslipidemia is currently recognized as a risk factor for atherosclerosis, which can easily cause coronary artery disease, cerebrovascular disease and peripheral vascular disease in the long term.
Studies have pointed out that every 40 mg/dl reduction in low-density lipoprotein cholesterol (LDL-c) can reduce major adverse cardiovascular events by 24%.
A systematic literature review and meta-analysis (32 studies with 14,515 participants) noted that zinc supplementation helped reduce a variety of lipids, including total cholesterol, LDL cholesterol, and triglycerides, with the most significant improvements in unhealthy populations (obesity, type 2 diabetes, end-stage renal failure, and hemodialysis). Note 8
The mechanism behind it is related to the ability of zinc to improve insulin secretion or reduce insulin resistance, which in turn affects lipid metabolism.
＊Conclusion: Zinc supplementation has the function of regulating blood lipids, especially for patients with metabolic syndrome.
Zinc is good for Parkinson’s disease
Parkinson’s disease is a neurodegenerative disease associated with aging, estimated to affect about 1% of the global population over 60 years of age, the most obvious features are motor tremors, stiffness, retardation, posture instability, etc.
Although the main pathogenesis is unknown, inflammation and oxidative stress play an important role, and zinc is an important cofactor in the formation of various antioxidant enzymes, which has the effect of fighting free radicals and protecting neurons from oxidative damage.
In addition, zinc is an important nutrient in the central nervous system, especially in the hippocampus and cerebral cortex is rich in zinc, if the deficiency can affect the balance state in the brain, resulting in changes in behavior, learning, memory and emotional stability.
A meta-analysis (23 studies, 1306 Parkinson’s cases, and 1294 control groups) found that Parkinson’s patients had lower levels of zinc in serum and plasma than healthy people. Note 9
＊Comment: Zinc deficiency is a potential risk factor for Parkinson’s disease, and zinc supplementation may become a potential therapy, and more studies are needed to confirm its clinical benefits in the future
Zinc improves tinnitus symptoms
Tinnitus is mainly defined as phantom auditory perception caused by no obvious sound stimulation, and the prevalence rate in adults can reach 25.3%, often causing inability to concentrate, insomnia, reduced language resolution, and even physical and mental symptoms such as depression and anxiety, which affects the quality of life
Observational studies have found that zinc deficiency is often associated with impaired hearing thresholds and the severity of tinnitus loudness. Note 10
A Cochrane Database of Systematic Reviews (3 studies, 209 participants) found that oral zinc did not lead to significant improvements in tinnitus symptoms in adults (measures including tinnitus disorder questionnaire, tinnitus loudness, overall severity). Note 11
*Conclusion: So far, there is no evidence that zinc can improve tinnitus symptoms, and limited by the small sample size and possible bias, more large-scale experiments with precise design are still needed for further verification
Zinc prevents prostate cancer
Prostate Cancer is a common malignant tumor disease in men, estimated to be about 180,000 new cases each year
In terms of pathological anatomy, the risk of prostate cancer in men between the ages of 40 and 49 is about 40%, and it increases to 70% by the age of 60 to 69
Although the physiological mechanism of zinc in the pathogenesis of prostate cancer has not been fully elucidated, evidence suggests that it is related to its inhibition of angiogenesis and metastasis potential of cancer cells
A meta-analysis (17 studies, 11,689 prostate cancer cases and 111,199 participants) pointed out that although most prostate cancers had insufficient zinc intake; However, so far, there is no clear association between dietary zinc intake and the incidence of prostate cancer. Note 14
*Summary: Zinc intake (either from food or supplements) does not prevent prostate cancer and is subject to further confirmation in larger epidemiological studies
What are the side effects of zinc?
Long-term use of zinc supplements, and below the tolerable upper intake (Tolerable Upper Intake Leve) is generally considered safe (the tolerable upper intake of zinc for adults is about 40 mg of elemental zinc).
The possible side effects of taking zinc are: stomach cramps, loss of appetite, irritability, nausea, vomiting, diarrhea, headache, metallic taste in the mouth, these symptoms usually relieve themselves.
Prolonged overdose (more than 50 mg or more) may trigger symptoms such as fever, fatigue, dizziness, headache, drowsiness, sweating, and low HDL
It has also been clinically found that taking more than 50 mg of zinc for 6 to 8 weeks may cause copper deficiency and cause copper deficiency symptoms (e.g., anemia, bone loss), so it is recommended to add 2 mg of copper to the formula to prevent this condition.
In addition, taking more than 100 mg of zinc for a long time not only has no benefits, but may also cause damage to the immune system and increase the incidence of prostate cancer (prostate cancer). Note 15
- In pregnant and lactating women with good nutritional status, the intake of zinc supplements should not exceed the tolerable upper limit (40 mg per day)
- Zinc may affect the efficacy of two types of antibiotics, such as tetracyclines and quinolone. Related drug names are: Ciprofloxacin, enoxacin, norfloxacin, sparfloxacin, trovafloxacin, grepafloxacin, demeclocycline, minocycline, tetracycline
- Do not take Amiloride (a diuretic) at the same time, it may cause high zinc levels in the blood
- ACE Inhibitors may reduce the concentration of zinc in the blood
- Do not use cisplatin together with the chemotherapy drug, which may affect the efficacy of the drug
- Do not take it with immunosuppressive agents, such as Cyclosporin, Prednisone, Porticosteroids (because zinc can enhance immunity)
- Do not use with penicillamine (common medication for Wilson’s disease and rheumatoid arthritis), as it may affect the efficacy of the drug
- When zinc, calcium, magnesium and iron are absorbed in the intestines, the same transporter will be used. If the transporter’s loading limit is exceeded, the absorption rate will decrease. Therefore, when these four minerals are taken at the same time, the total is best Less than 800 mg.
Food sources of zinc and recommended dosage
Natural food sources of zinc mainly come from animal protein, the most abundant is oysters, followed by red meat, liver, fish, shrimp, eggs, etc., while plant sources are mainly cereals and legumes (but the absorption rate is poor).
As for the recommended dose of zinc, according to the US RDA (Recommended Daily Diet), adult men and women need 11 mg and 8 mg respectively, pregnant and nursing mothers need to increase to 13 mg, and children range from 3 mg to 9 mg