בכד לחסל את הקרונה צריך לקחת הרבה וטימין D ואבץ COVID-19 and Zinc

https://www.wsj.com/articles/trump-takes-zinc-maybe-you-should-too-11601916665

[size=54]Trump Takes Zinc. Maybe You Should Too[/size]

Research suggests the mineral bolsters the immune system against Covid and other diseases.

President Trump is getting state-of-the-art care for his coronavirus infection, including the antiviral drug remdesivir and a monoclonal-antibody cocktail. Most Americans have limited access to these therapies. The antibody treatment hasn’t been approved by the Food and Drug Administration even for emergency use, so it’s available only to patients in clinical trials or on a case by case basis for compassionate use if approved by the FDA and drug manufacturer Regeneron. Remdesivir must be administered in a hospital, and patients often aren’t admitted until days after they develop severe symptoms.
But Mr. Trump is receiving one treatment you can buy without a prescription at your local drugstore: zinc. Last month, researchers from Spain reported that patients who died in hospitals in March and April on average had zinc blood levels of 43 micrograms per deciliter; survivors had 63. A level of 70 is considered normal. After adjusting for age, sex, illness severity and treatments, every unit increase of zinc in the blood was associated with a 7% lower likelihood of dying. That’s huge.
Zinc plays a critical role in regulating metabolism and the immune system. Over the years, many studies have found that people with low levels are more likely to develop pneumonia and recurring sepsis as well as suffer from conditions such as diabetes, kidney disease and chronic fatigue syndrome.
Severe zinc deficiency “depresses immune function,” the National Institutes of Health explains in a fact sheet for health professionals. “Even mild to moderate degrees of zinc deficiency can impair macrophage and neutrophil functions, natural killer cell activity, and complement activity. The body requires zinc to develop and activate T-lymphocytes.” Many of these issues “can be corrected by zinc
Usually an infectious agent will spur the body to produce more white blood cells, but severely ill Covid-19 patients tend to have low levels of lymphocytes. Antibody treatments like the one Mr. Trump is receiving are in part intended to compensate for a sluggish immune response in the earlier stages of the disease that later can result in an inflammatory “cytokine storm.”


Older people often have low zinc levels. One reason is their diets don’t include enough foods with zinc. Red meat is the best dietary source, but many older people avoid beef because they have a heart condition or are trying to prevent one. Whole grains, beans and nuts have zinc, but they include phytates that inhibit its absorption. The NIH notes that vegetarians may require at least 50% more zinc than nonvegetarians. Calcium supplements, which many postmenopausal women take to boost bone density, may also inhibit zinc absorption. Conditions like diabetes, kidney disease and ulcerative colitis can also reduce zinc absorption and increase its excretion. So can medications for hypertension.
A seminal clinical trial tracked nursing-home patients in Massachusetts from 1998 to 2001 who received a multivitamin supplement that included 50% of the recommended intake of zinc. Patients with normal levels of zinc at the start of the trial were 40% less likely to die from any cause. But the incidence of pneumonia was 50% lower during the trial in patients who had normal zinc levels at the study’s end. “Severe zinc deficiency can impair immunity and increase susceptibility to infectious diseases, a major cause of mortality in the elderly,” the study noted.

A recent article in the Journal of Medical Virology hypothesizes that zinc may also have an antiviral effect against Covid-19 because zinc may inhibit other RNA viruses, including coronaviruses. In a 2010 study, zinc coupled with an ionophore (a chemical that transports an ion across a cell membrane) was found to inhibit the replication of SARS.
Some Covid-19 studies have also shown promising results from pairing zinc with the antimalaria drug hydroxychloriquine (HCQ), another ionophore. A study of hospitalized patients in New York found that those treated with zinc on top of HCQ and the antibiotic azithromycin were about half as likely to die or be transferred to a hospice than those who didn’t receive zinc.
It is possible that the disparate results from studies evaluating HCQ as a Covid-19 treatment may be explained in part by zinc: People with inadequate zinc levels may simply not derive an antiviral benefit from the malaria drug. Those who have high-functioning immune systems may be able to defeat the virus without the help of drugs.
Healthy adults generally don’t suffer from zinc deficiencies so might not benefit from taking a supplement. Most people with adequate levels of zinc in their blood will excrete excess amounts or simply not absorb it in their guts. But people who are most vulnerable to the virus also tend to have zinc deficiencies, and this could help explain why some people infected with the virus get severely ill while others have mild or no symptoms. It certainly deserves more study. In any case, most Americans would do well to make sure they’re getting enough of the essential mineral.
Ms. Finley is a member of the Journal’s editorial board.

[size=33]Zinc[/size]
Fact Sheet for Health Professionals
https://ods.od.nih.gov/factsheets/Zinc-HealthProfessional/



This is a fact sheet intended for health professionals. For a reader-friendly overview of Zinc, see our consumer fact sheet on Zinc.

Introduction

Zinc is an essential mineral that is naturally present in some foods, added to others, and available as a dietary supplement. Zinc is also found in many cold lozenges and some over-the-counter drugs sold as cold remedies.
Zinc is involved in numerous aspects of cellular metabolism. It is required for the catalytic activity of approximately 100 enzymes [1,2] and it plays a role in immune function [3,4], protein synthesis [4], wound healing [5], DNA synthesis [2,4], and cell division [4]. Zinc also supports normal growth and development during pregnancy, childhood, and adolescence [6-8] and is required for proper sense of taste and smell [9]. A daily intake of zinc is required to maintain a steady state because the body has no specialized zinc storage system [10].

Recommended Intakes

Intake recommendations for zinc and other nutrients are provided in the Dietary Reference Intakes (DRIs) developed by the Food and Nutrition Board (FNB) at the Institute of Medicine of the National Academies (formerly National Academy of Sciences) [2]. DRI is the general term for a set of reference values used for planning and assessing nutrient intakes of healthy people. These values, which vary by age and gender [2], include the following:

• Recommended Dietary Allowance (RDA): Average daily level of intake sufficient to meet the nutrient requirements of nearly all (97%–98%) healthy individuals; often used to plan nutritionally adequate diets for individuals.
  
  
• Adequate Intake (AI): Intake at this level is assumed to ensure nutritional adequacy; established when evidence is insufficient to develop an RDA.
  
  
• Estimated Average Requirement (EAR): Average daily level of intake estimated to meet the requirements of 50% of healthy individuals; usually used to assess the nutrient intakes of groups of people and to plan nutritionally adequate diets for them; can also be used to assess the nutrient intakes of individuals.
  
  
• Tolerable Upper Intake Level (UL): Maximum daily intake unlikely to cause adverse health effects.
  
  

The current RDAs for zinc are listed in Table 1 [2]. For infants aged 0 to 6 months, the FNB established an AI for zinc that is equivalent to the mean intake of zinc in healthy, breastfed infants.
Table 1: Recommended Dietary Allowances (RDAs) for Zinc [2][th]Age[/th][th]Male[/th][th]Female[/th][th]Pregnancy[/th][th]Lactation[/th]

0–6 months	2 mg*	2 mg*
7–12 months	3 mg	3 mg
1–3 years	3 mg	3 mg
4–8 years	5 mg	5 mg
9–13 years	8 mg	8 mg
14–18 years	11 mg	9 mg	12 mg	13 mg
19+ years	11 mg	8 mg	11 mg	12 mg

* Adequate Intake (AI)

Sources of Zinc

Food

A wide variety of foods contain zinc (Table 2) [2]. Oysters contain more zinc per serving than any other food, but red meat and poultry provide the majority of zinc in the American diet. Other good food sources include beans, nuts, certain types of seafood (such as crab and lobster), whole grains, fortified breakfast cereals, and dairy products [2,11].
Phytates—which are present in whole-grain breads, cereals, legumes, and other foods—bind zinc and inhibit its absorption [2,12,13]. Thus, the bioavailability of zinc from grains and plant foods is lower than that from animal foods, although many grain- and plant-based foods are still good sources of zinc [2].
Table 2: Selected Food Sources of Zinc [11][th]Food[/th][th]Milligrams (mg)per serving[/th][th]Percent DV*[/th]

Oysters, cooked, breaded and fried, 3 ounces	74.0	673
Beef chuck roast, braised, 3 ounces	7.0	64
Crab, Alaska king, cooked, 3 ounces	6.5	59
Beef patty, broiled, 3 ounces	5.3	48
Lobster, cooked, 3 ounces	3.4	31
Pork chop, loin, cooked, 3 ounces	2.9	26
Baked beans, canned, plain or vegetarian, ½ cup	2.9	26
Breakfast cereal, fortified with 25% of the DV for zinc, 1 serving	2.8	25
Chicken, dark meat, cooked, 3 ounces	2.4	22
Pumpkin seeds, dried, 1 ounce	2.2	20
Yogurt, fruit, low fat, 8 ounces	1.7	15
Cashews, dry roasted, 1 ounce	1.6	15
Chickpeas, cooked, ½ cup	1.3	12
Cheese, Swiss, 1 ounce	1.2	11
Oatmeal, instant, plain, prepared with water, 1 packet	1.1	10
Milk, low-fat or non fat, 1 cup	1.0	9
Almonds, dry roasted, 1 ounce	0.9	8
Kidney beans, cooked, ½ cup	0.9	8
Chicken breast, roasted, skin removed, ½ breast	0.9	8
Cheese, cheddar or mozzarella, 1 ounce	0.9	8
Peas, green, frozen, cooked, ½ cup	0.5	5
Flounder or sole, cooked, 3 ounces	0.3	3

 
* DV = Daily Value. The U.S. Food and Drug Administration (FDA) developed DVs to help consumers compare the nutrient contents of foods and dietary supplements within the context of a total diet. The DV for zinc on the new Nutrition Facts and Supplement Facts labels and used for the values in Table 2 is 11 mg for adults and children aged 4 years and older [15]. FDA required manufacturers to use these new labels starting in January 2020, but companies with annual sales of less than $10 million may continue to use the old labels that list a zinc DV of 15 mg until January 2021 [14,16]. FDA does not require food labels to list zinc content unless zinc has been added to the food. Foods providing 20% or more of the DV are considered to be high sources of a nutrient, but foods providing lower percentages of the DV also contribute to a healthful diet.
The U.S. Department of Agriculture’s (USDA’s) FoodData Central [11] lists the nutrient content of many foods and provides a comprehensive list of foods containing zinc arranged by nutrient content and by food name.

Dietary supplements

Supplements contain several forms of zinc, including zinc gluconate, zinc sulfate, and zinc acetate. The percentage of elemental zinc varies by form. For example, approximately 23% of zinc sulfate consists of elemental zinc; thus, 220 mg of zinc sulfate contains 50 mg of elemental zinc. The elemental zinc content appears in the Supplement Facts panel on the supplement container. Research has not determined whether differences exist among forms of zinc in absorption, bioavailability, or tolerability.
In addition to standard tablets and capsules, some zinc-containing cold lozenges are labeled as dietary supplements.

Other sources

Zinc is present in several products, including some labeled as homeopathic medications, sold over the counter for the treatment and prevention of colds. Numerous case reports of anosmia (loss of the sense of smell), in some cases long-lasting or permanent, have been associated with the use of zinc-containing nasal gels or sprays [17,18]. In June 2009, the FDA warned consumers to stop using three zinc-containing intranasal products because they might cause anosmia [19]. The manufacturer recalled these products from the marketplace. Currently, these safety concerns have not been found to be associated with cold lozenges containing zinc.
Zinc is also present in some denture adhesive creams at levels ranging from 17–34 mg/g [20]. While use of these products as directed (0.5–1.5 g/day) is not of concern, chronic, excessive use can lead to zinc toxicity, resulting in copper deficiency and neurologic disease. Such toxicity has been reported in individuals who used 2 or more standard 2.4 oz tubes of denture cream per week [20,21]. Many denture creams have now been reformulated to eliminate zinc.

Zinc Intakes and Status

Most infants (especially those who are formula fed), children, and adults in the United States consume recommended amounts of zinc according to two national surveys, the 1988–1991 National Health and Nutrition Examination Survey (NHANES III) [22] and the 1994 Continuing Survey of Food Intakes of Individuals (CSFII) [23].
However, some evidence suggests that zinc intakes among older adults might be marginal. An analysis of NHANES III data found that 35%–45% of adults aged 60 years or older had zinc intakes below the estimated average requirement of 6.8 mg/day for elderly females and 9.4 mg/day for elderly males. When the investigators considered intakes from both food and dietary supplements, they found that 20%–25% of older adults still had inadequate zinc intakes [24].

Zinc intakes might also be low in older adults from the 2%–4% of U.S. households that are food insufficient (sometimes or often not having enough food) [25]. Data from NHANES III indicate that adults aged 60 years or older from food-insufficient families had lower intakes of zinc and several other nutrients and were more likely to have zinc intakes below 50% of the RDA on a given day than those from food-sufficient families [26].

Zinc Deficiency

Zinc deficiency is characterized by growth retardation, loss of appetite, and impaired immune function. In more severe cases, zinc deficiency causes hair loss, diarrhea, delayed sexual maturation, impotence, hypogonadism in males, and eye and skin lesions [2,8,27,28]. Weight loss, delayed healing of wounds, taste abnormalities, and mental lethargy can also occur [5,8,29-33]. Many of these symptoms are non-specific and often associated with other health conditions; therefore, a medical examination is necessary to ascertain whether a zinc deficiency is present.
Zinc nutritional status is difficult to measure adequately using laboratory tests [2,34,35] due to its distribution throughout the body as a component of various proteins and nucleic acids [36]. Plasma or serum zinc levels are the most commonly used indices for evaluating zinc deficiency, but these levels do not necessarily reflect cellular zinc status due to tight homeostatic control mechanisms [8]. Clinical effects of zinc deficiency can be present in the absence of abnormal laboratory indices [8]. Clinicians consider risk factors (such as inadequate caloric intake, alcoholism, and digestive diseases) and symptoms of zinc deficiency (such as impaired growth in infants and children) when determining the need for zinc supplementation [2].

Groups at Risk of Zinc Inadequacy

In North America, overt zinc deficiency is uncommon [2]. When zinc deficiency does occur, it is usually due to inadequate zinc intake or absorption, increased losses of zinc from the body, or increased requirements for zinc [29,30,37]. People at risk of zinc deficiency or inadequacy need to include good sources of zinc in their daily diets. Supplemental zinc might also be appropriate in certain situations.

People with gastrointestinal and other diseases

Gastrointestinal surgery and digestive disorders (such as ulcerative colitis, Crohn’s disease, and short bowel syndrome) can decrease zinc absorption and increase endogenous zinc losses primarily from the gastrointestinal tract and, to a lesser extent, from the kidney [2,29,38,39]. Other diseases associated with zinc deficiency include malabsorption syndrome, chronic liver disease, chronic renal disease, sickle cell disease, diabetes, malignancy, and other chronic illnesses [40]. Chronic diarrhea also leads to excessive loss of zinc [27].

Vegetarians

The bioavailability of zinc from vegetarian diets is lower than from non-vegetarian diets because vegetarians do not eat meat, which is high in bioavailable zinc and may enhance zinc absorption. In addition, vegetarians typically eat high levels of legumes and whole grains, which contain phytates that bind zinc and inhibit its absorption [34,41].
Vegetarians sometimes require as much as 50% more of the RDA for zinc than non-vegetarians [2]. In addition, they might benefit from using certain food preparation techniques that reduce the binding of zinc by phytates and increase its bioavailability. Techniques to increase zinc bioavailability include soaking beans, grains, and seeds in water for several hours before cooking them and allowing them to sit after soaking until sprouts form [41]. Vegetarians can also increase their zinc intake by consuming more leavened grain products (such as bread) than unleavened products (such as crackers) because leavening partially breaks down the phytate; thus, the body absorbs more zinc from leavened grains than unleavened grains.

Pregnant and lactating women

Pregnant women, particularly those starting their pregnancy with marginal zinc status, are at increased risk of becoming zinc insufficient due, in part, to high fetal requirements for zinc [42]. Lactation can also deplete maternal zinc stores [43]. For these reasons, the RDA for zinc is higher for pregnant and lactating women than for other women (see Table 1) [2].

Older infants who are exclusively breastfed

Breast milk provides sufficient zinc (2 mg/day) for the first 4–6 months of life but does not provide recommended amounts of zinc for infants aged 7–12 months, who need 3 mg/day [2,36]. In addition to breast milk, infants aged 7–12 months should consume age-appropriate foods or formula containing zinc [2]. Zinc supplementation has improved the growth rate in some children who demonstrate mild-to-moderate growth failure and who have a zinc deficiency [27,44].

People with sickle cell disease

Results from a large cross-sectional survey suggest that 44% of children with sickle cell disease have a low plasma zinc concentration [45], possibly due to increased nutrient requirements and/or poor nutritional status [46]. Zinc deficiency also affects approximately 60%–70% of adults with sickle cell disease [47]. Zinc supplementation has been shown to improve growth in children with sickle cell disease [46].

Alcoholics

Approximately 30%–50% of alcoholics have low zinc status because ethanol consumption decreases intestinal absorption of zinc and increases urinary zinc excretion [47]. In addition, the variety and amount of food consumed by many alcoholics is limited, leading to inadequate zinc intake [2,49,50].

Zinc and Health

Immune function

Severe zinc deficiency depresses immune function [51], and even mild to moderate degrees of zinc deficiency can impair macrophage and neutrophil functions, natural killer cell activity, and complement activity [52]. The body requires zinc to develop and activate T-lymphocytes [2,53]. Individuals with low zinc levels have shown reduced lymphocyte proliferation response to mitogens and other adverse alterations in immunity that can be corrected by zinc supplementation [52,54]. These alterations in immune function might explain why low zinc status has been associated with increased susceptibility to pneumonia and other infections in children in developing countries and the elderly [55-58].

Wound healing

Zinc helps maintain the integrity of skin and mucosal membranes [52]. Patients with chronic leg ulcers have abnormal zinc metabolism and low serum zinc levels [59], and clinicians frequently treat skin ulcers with zinc supplements [60]. The authors of a systematic review concluded that zinc sulfate might be effective for treating leg ulcers in some patients who have low serum zinc levels [61,62]. However, research has not shown that the general use of zinc sulfate in patients with chronic leg ulcers or arterial or venous ulcers is effective [61,62].

Diarrhea

Acute diarrhea is associated with high rates of mortality among children in developing countries [63]. Zinc deficiency causes alterations in immune response that probably contribute to increased susceptibility to infections, such as those that cause diarrhea, especially in children [52].
Studies show that poor, malnourished children in India, Africa, South America, and Southeast Asia experience shorter courses of infectious diarrhea after taking zinc supplements [64]. The children in these studies received 4–40 mg of zinc a day in the form of zinc acetate, zinc gluconate, or zinc sulfate [64].
In addition, results from a pooled analysis of randomized controlled trials of zinc supplementation in developing countries suggest that zinc helps reduce the duration and severity of diarrhea in zinc-deficient or otherwise malnourished children [65]. Similar findings were reported in a meta-analysis published in 2008 and a 2007 review of zinc supplementation for preventing and treating diarrhea [66,67]. The effects of zinc supplementation on diarrhea in children with adequate zinc status, such as most children in the United States, are not clear.
The World Health Organization and UNICEF now recommend short-term zinc supplementation (20 mg of zinc per day, or 10 mg for infants under 6 months, for 10–14 days) to treat acute childhood diarrhea [63].

The common cold

Researchers have hypothesized that zinc could reduce the severity and duration of cold symptoms by directly inhibiting rhinovirus binding and replication in the nasal mucosa and suppressing inflammation [68,69]. Although studies examining the effect of zinc treatment on cold symptoms have had somewhat conflicting results, overall zinc appears to be beneficial under certain circumstances. Several studies are described below in which zinc is administered as a lozenge or zinc-containing syrup that temporarily “sticks” in the mouth and throat. This allows zinc to make contact with the rhinovirus in those areas.
In a randomized, double-blind, placebo-controlled clinical trial, 50 subjects (within 24 hours of developing the common cold) took a zinc acetate lozenge (13.3 mg zinc) or placebo every 2–3 wakeful hours. Compared with placebo, the zinc lozenges significantly reduced the duration of cold symptoms (cough, nasal discharge, and muscle aches) [70].
In another clinical trial involving 273 participants with experimentally induced colds, zinc gluconate lozenges (providing 13.3 mg zinc) significantly reduced the duration of illness compared with placebo but had no effect on symptom severity [71]. However, treatment with zinc acetate lozenges (providing 5 or 11.5 mg zinc) had no effect on either cold duration or severity. Neither zinc gluconate nor zinc acetate lozenges affected the duration or severity of cold symptoms in 281 subjects with natural (not experimentally induced) colds in another trial [71].
In 77 participants with natural colds, a combination of zinc gluconate nasal spray and zinc orotate lozenges (37 mg zinc every 2–3 wakeful hours) was also found to have no effect on the number of asymptomatic patients after 7 days of treatment [72].
In September of 2007, Caruso and colleagues published a structured review of the effects of zinc lozenges, nasal sprays, and nasal gels on the common cold [69]. Of the 14 randomized, placebo-controlled studies included, 7 (5 using zinc lozenges, 2 using a nasal gel) showed that the zinc treatment had a beneficial effect and 7 (5 using zinc lozenges, 1 using a nasal spray, and 1 using lozenges and a nasal spray) showed no effect.
More recently, a Cochrane review concluded that “zinc (lozenges or syrup) is beneficial in reducing the duration and severity of the common cold in healthy people, when taken within 24 hours of onset of symptoms” [73]. The author of another review completed in 2004 also concluded that zinc can reduce the duration and severity of cold symptoms [68]. However, more research is needed to determine the optimal dosage, zinc formulation and duration of treatment before a general recommendation for zinc in the treatment of the common cold can be made [73].
As previously noted, the safety of intranasal zinc has been called into question because of numerous reports of anosmia (loss of smell), in some cases long-lasting or permanent, from the use of zinc-containing nasal gels or sprays [17-19].

Age-related macular degeneration

Researchers have suggested that both zinc and antioxidants delay the progression of age-related macular degeneration (AMD) and vision loss, possibly by preventing cellular damage in the retina [74,75]. In a population-based cohort study in the Netherlands, high dietary intake of zinc as well as beta carotene, vitamin C, and vitamin E was associated with reduced risk of AMD in elderly subjects [76]. However, the authors of a systematic review and meta-analysis published in 2007 concluded that zinc is not effective for the primary prevention of early AMD [77], although zinc might reduce the risk of progression to advanced AMD.
The Age-Related Eye Disease Study (AREDS), a large, randomized, placebo-controlled, clinical trial (n = 3,597), evaluated the effect of high doses of selected antioxidants (500 mg vitamin C, 400 IU vitamin E, and 15 mg beta-carotene) with or without zinc (80 mg as zinc oxide) on the development of advanced AMD in older individuals with varying degrees of AMD [75]. Participants also received 2 mg copper to prevent the copper deficiency associated with high zinc intakes. After an average follow-up period of 6.3 years, supplementation with antioxidants plus zinc (but not antioxidants alone) significantly reduced the risk of developing advanced AMD and reduced visual acuity loss. Zinc supplementation alone significantly reduced the risk of developing advanced AMD in subjects at higher risk but not in the total study population. Visual acuity loss was not significantly affected by zinc supplementation alone.
A follow-up AREDS2 study confirmed the value of this supplement in reducing the progression of AMD over a median follow-up period of 5 years [78]. AREDS2 found that a formulation providing 25 mg zinc (about one-third the amount in the original formulation) provided the same protective effect against developing advanced AMD. However, because AREDS2 had fewer participants than the original AREDS study, and fewer than half took the lower zinc formula, the researchers view this finding as preliminary. They recommend use of an AREDS formulation providing 80 mg zinc [79,80].
Two other small clinical trials evaluated the effects of supplementation with 200 mg zinc sulfate (providing 45 mg zinc) for 2 years in subjects with drusen or macular degeneration. Zinc supplementation significantly reduced visual acuity loss in one of the studies [81] but had no effect in the other [82].
A Cochrane review concluded that the evidence supporting the use of antioxidant vitamins and zinc for AMD comes primarily from the AREDS study [74]. Individuals who have or are developing AMD should talk to their healthcare provider about taking a zinc-containing AREDS supplement.

Interactions with iron and copper

Iron-deficiency anemia is a serious world-wide public health problem. Iron fortification programs have been credited with improving the iron status of millions of women, infants, and children. Fortification of foods with iron does not significantly affect zinc absorption. However, large amounts of supplemental iron (greater than 25 mg) might decrease zinc absorption [2,83]. Taking iron supplements between meals helps decrease its effect on zinc absorption [83].
High zinc intakes can inhibit copper absorption, sometimes producing copper deficiency and associated anemia [84,85]. For this reason, dietary supplement formulations containing high levels of zinc, such as the one used in the AREDS study [75], sometimes contain copper.

Health Risks from Excessive Zinc

Zinc toxicity can occur in both acute and chronic forms. Acute adverse effects of high zinc intake include nausea, vomiting, loss of appetite, abdominal cramps, diarrhea, and headaches [2]. One case report cited severe nausea and vomiting within 30 minutes of ingesting 4 g of zinc gluconate (570 mg elemental zinc) [86]. Intakes of 150–450 mg of zinc per day have been associated with such chronic effects as low copper status, altered iron function, reduced immune function, and reduced levels of high-density lipoproteins [87]. Reductions in a copper-containing enzyme, a marker of copper status, have been reported with even moderately high zinc intakes of approximately 60 mg/day for up to 10 weeks [2]. The doses of zinc used in the AREDS study (80 mg per day of zinc in the form of zinc oxide for 6.3 years, on average) have been associated with a significant increase in hospitalizations for genitourinary causes, raising the possibility that chronically high intakes of zinc adversely affect some aspects of urinary physiology [88].
The FNB has established ULs for zinc (Table 3). Long-term intakes above the UL increase the risk of adverse health effects [2]. The ULs do not apply to individuals receiving zinc for medical treatment, but such individuals should be under the care of a physician who monitors them for adverse health effects.
Table 3: Tolerable Upper Intake Levels (ULs) for Zinc [2][th]Age[/th][th]Male[/th][th]Female[/th][th]Pregnant[/th][th]Lactating[/th]

0–6 months	4 mg	4 mg
7–12 months	5 mg	5 mg
1–3 years	7 mg	7 mg
4–8 years	12 mg	12 mg
9–13 years	23 mg	23 mg
14–18 years	34 mg	34 mg	34 mg	34 mg
19+ years	40 mg	40 mg	40 mg	40 mg

Interactions with Medications

Zinc supplements have the potential to interact with several types of medications. A few examples are provided below. Individuals taking these medications on a regular basis should discuss their zinc intakes with their healthcare providers.

Antibiotics

Both quinolone antibiotics (such as Cipro:registered:) and tetracycline antibiotics (such as Achromycin:registered: and Sumycin:registered:) interact with zinc in the gastrointestinal tract, inhibiting the absorption of both zinc and the antibiotic [89,90]. Taking the antibiotic at least 2 hours before or 4–6 hours after taking a zinc supplement minimizes this interaction [91].

Penicillamine

Zinc can reduce the absorption and action of penicillamine, a drug used to treat rheumatoid arthritis [92]. To minimize this interaction, individuals should take zinc supplements at least 2 hours before or after taking penicillamine [90].

Diuretics

Thiazide diuretics such as chlorthalidone (Hygroton:registered:) and hydrochlorothiazide (Esidrix:registered: and HydroDIURIL:registered:) increase urinary zinc excretion by as much as 60% [93]. Prolonged use of thiazide diuretics could deplete zinc tissue levels, so clinicians should monitor zinc status in patients taking these medications.

Zinc and Healthful Diets

The federal government’s 2015-2020 Dietary Guidelines for Americans notes that “Nutritional needs should be met primarily from foods. … Foods in nutrient-dense forms contain essential vitamins and minerals and also dietary fiber and other naturally occurring substances that may have positive health effects. In some cases, fortified foods and dietary supplements may be useful in providing one or more nutrients that otherwise may be consumed in less-than-recommended amounts.”
For more information about building a healthy diet, refer to the Dietary Guidelines for Americans and the U.S. Department of Agriculture’s MyPlate.
The Dietary Guidelines for Americans describes a healthy eating pattern as one that:

• Includes a variety of vegetables, fruits, whole grains, fat-free or low-fat milk and milk products, and oils.Whole grains and milk products are good sources of zinc. Many ready-to-eat breakfast cereals are fortified with zinc.
  
  
• Includes a variety of protein foods, including seafood, lean meats and poultry, eggs, legumes (beans and peas), nuts, seeds, and soy products.Oysters, red meat, and poultry are excellent sources of zinc. Baked beans, chickpeas, and nuts (such as cashews and almonds) also contain zinc.
  
  
• Limits saturated and trans fats, added sugars, and sodium.
  
  
• Stays within your daily calorie needs.
  
  

Serum zinc and pneumonia in nursing home elderly
https://onlinelibrary.wiley.com/doi/10.1002/jmv.26523
Potential interventions for SARS‐CoV‐2 infections: Zinc showing promise

Highlights

Zinc (Zn) inhibits SARS‐CoV‐2 in vitro by several different mechanism. Zn deficiency may increase the risk for severity of COVID‐19 infection. The addition of Zn, particularly with a Zn ionophore, shows substantial promise as a treatment regimen.



In the early weeks of the coronavirus disease 2019 (COVID‐19) pandemic, Zang and Yunhui discussed in the Journal of Medical Virology various treatment approaches as potential interventions against the virus including zinc (Zn).[size=15]1 In the six months since that publication, information has emerged that Zn may be important for natural protection against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) severity, as well as an effective tool for treatment.[/size]

Intracellular elemental zinc (Zn) inhibits various RNA viruses including coronaviruses.[size=15]2 In a 2010 study, Zn coupled with an Zn ionophore (pyrithione), showed potent inhibition of SARS‐CoV replication (even at very low micromolar concentrations). Zn directly inhibited the coronaviral RNA‐dependent RNA polymerase, which functions as the core enzyme of the RNA viral synthesizing machinery.2 Zn also inhibits SARS‐CoV papain‐like protease 2, which is also a key enzyme for viral replication and assembly of functional viral proteins.3 Zn and several Zn chelates were shown to inhibit furin (proprotein convertase) which is important in the pathogenesis of many viruses.4 The furin proteases have been proposed as therapeutic targets for several viral pathogens.5 Specifically, the spike glycoprotein of SARS‐CoV‐2 contains a unique furin cleavage site that is not found in SARS‐CoV.6 This furin activation mechanism increases the infectivity and pathogenicity of viruses.6 Zn inhibition of host furin in SARS‐CoV‐2 infection may be an important antiviral mechanism unique to this novel strain.[/size]

Chloroquine has been shown to be a potent Zn ionophore and transports Zn through the cell membrane substantially increasing intracellular levels of Zn, especially in the endosomal‐lysosomal compartment.[size=15]7 These same ionophore properties presumably apply to the closely related molecule, hydroxychloroquine (HCQ). Interestingly, coronaviruses enter cells via lysosomes or endosomes which requires proteolysis.8[/size]

There are other important mechanisms of Zn activity for viruses, likely including SARS‐CoV‐2: anti‐inflammatory and/or immune modulation, altered receptor binding and expres​sion(e.g., ACE2), among others.[size=15]9, 10[/size]

Zn is not stored in the body, thus, must be obtained through the diet or supplements. The adult RDA for elemental Zn is 11 mg per day.[size=15]11 Zn has been shown to be an important factor in respiratory viral pathogenesis or infections and Zn has been widely studied as a treatment for viral URIs.9, 10 Global prevalence of Zn deficiency may be as high as 20%.9 Zn deficiency has been demonstrated in diabetics and with increasing age.10, 12 It has been estimated that 35% to 45% of adults ≥60 years have Zn intakes below the estimated average requirement.12 Almost 60% of elderly and nursing home residents in the U.S. showed decreased Zn intake levels.10 Additionally, antihypertensive medications can increase urinary excretion of Zn.10, 12 These conditions, associated with lower Zn levels, are now well recognized risk factors for severity of COVID‐19 infection.10[/size]

Persistent low Zn levels have been found in critically ill patients and is associated with recurrent sepsis.[size=15]13 It is not clear as to whether the low levels were present before sepsis or was part of the acute illness. Either way, given that Zn has multiple roles in the defenses against COVID‐19, such low levels are likely to be present in severe, critically ill COVID‐19 patients. This could contribute to slow clearance of the virus and the severity of the illness. Thus, it is postulated that Zn deficiency may pose a risk factor for COVID‐19 severity.12[/size]

For Zn supplementation or treatment, several Zn compounds are available, mainly Zn salts. The amount of elemental Zn in these supplements ranges from 15% to 30%. An informal survey of common retail pharmacies by one of the authors, showed that Zn gluconate was the most common form sold (several different brands). These Zn salts, including Zn gluconate, usually list the amount of Zn as milligrams of elemental Zn and percent of RDA. As an example, Zn gluconate is often available as 50 mg of elemental Zn. Zn gluconate and Zn sulfate (discussed in the studies below) are well absorbed and recommended by the WHO to treat Zn loss from diarrhea.[size=15]14 The most common adverse effects of Zn include nausea, vomiting, diarrhea and metallic taste. Potential drug interations with Zn for which the clinician should be aware include certain antibiotics (flouroquinolones, tetracyclines), cisplatin and penicillamine.15[/size]

A study of hospitalized COVID‐19 patients analyzed Zn as an add‐on therapy to HCQ‐azithromycin (AZ) combination.[size=15]16 HCQ dosing was 400 mg on day one and then 200 mg BID for 5 days. The Zn used was zinc sulfate, 220 mg (50 mg of elemental Zn) po BID, also for 5 days. They found an increased frequency of being discharged home (odds ratio [OR]: 1.5; 95% confidence interval [CI]: 1.12–2.09; p < .008) and reduction in mortality or transfer to hospice (OR: 0.449; 95% CI: 0.271–0.744; p < .002) in those patients (non‐intensive care unit [ICU]) who received Zn add‐on compared to those that did not receive Zn.[/size]

A study using a combination of Zn, low‐dose HCQ, and AZ for treatment of COVID‐19 in outpatients also showed promising results.[size=15]17 The doses were: zinc sulfate 220 mg once daily, HCQ 200 mg BID and AZ 500 mg daily, all for 5 days. This study compared 141 risk‐stratified COVID‐19 patients (from a larger pool of all COVID‐19 positives in the practice) treated with the triple regimen compared to 377 confirmed COVID‐19 patients from the same community (other practices) that were used as untreated controls. Risk‐stratified patients that met the criteria for treatment included: (A) age >60 years, with or without symptoms; (B) age <60 with shortness of breath; (C) age <60 with at least one of several comorbidities. Median time between symptom onset and consultation was 4 days. Of the treated patients, 4 of 141 (2.8%) were hospitalized compared to 58 of 377 (15.4%) of the untreated patients (OR: 0.16; 95% CI: 0.06–0.5, p < .001). In terms of mortality, one patient (0.7%) in the treated group died versus 13 (3.5%) in the untreated group (OR: 0.2; 95% CI: 0.03–1.5; p = .16). Thus, there was an 84% reduction in hospitalizations and 80% decrease in mortality. Nausea and diarrhea were reported in 14% and 11%, respectively. No cardiac adverse effects were noted.[/size]

A key antiviral mechanism for these triple combinations may be the Zn inhibition of the SARS‐CoV‐2 virus. HCQ likely acts as a potent Zn ionophore.

There are other Zn ionophores available as dietary supplements. Examples are quercetin and epigallocatechin‐gallate (ECGC), both bioflavonoids, which have been shown to be Zn ionophores.[size=15]18[/size]

Zn, in the presence of a Zn ionophore (such as HCQ), shows potent antiviral activity in vitro against coronaviruses, such as SARS‐CoV. This activity likely extends to SARS‐CoV‐2 and may potentially involve at least three different antiviral mechanisms discussed above. Zn deficiency may be associated with COVID‐19 severity during infection and increase the risk of severity when present before infection. Maintaining normal Zn levels may help prevent illness severity in COVID‐19 infection. An additional mechanism of HCQ activity in COVID‐19 patients may be the Zn ionophore effect. Supplemental Zn has been shown to act together with HCQ (presumably acting as a Zn ionophore) in clinical studies of COVID‐19 patients: demonstrating decrease hospitalizations, increased discharge in treated inpatients and decreased mortality. The elemental Zn dose in these studies was 50–100 mg per day (as Zn sulfate). Zn should be considered as an add‐on to HCQ treatment regimens (at least 50 mg elemental Zn equivalent, based on above studies). Zn could potentially allow for short courses and low doses of HCQ, yet remain a highly effective regimen. As demonstrated in the treatment studies above, early therapy (outpatients) should be a target population. However, there was substantial benefit in hospitalized patients, especially if not severe enough to be in the ICU. Since Zn has shown these promising results with treatment of SARS‐CoV‐2 infection, it is tempting to speculate that Zn could be used for prophylaxis, particularly when paired with an ionophore such as HCQ. Other Zn ionophores, such as quercetin or ECGC, may have a role in early treatment and/or prophylaxis, when coupled with Zn. These combinations have not been studied thus far (Figure 1).

Figure 1
Open in figure viewerPowerPoint

Potential Interventions for SARS‐CoV‐2 Infections. (A) Several ionophores can effectively transport Zn through the cell membrane. (B) Zn and Zn chelates inhibit furin, preventing a unique furin cleavage in the S protein of SARS‐CoV‐2 that is not found in SARS‐CoV. (C) Zn may also alter receptor binding and expression of ACE2. (D) Intracellular Zn directly inhibits RdRp and PLP2, which act as key enzymes for viral replication and assembly of functional viral proteins. Created with BioRender. com. ACE2, angiotensin converting enzyme 2; CQ/HCQ, cloroquine/hydroxycloroquine; PLP2, papain‐like protease 2; RdRp: RNA‐dependent RNA polymerase

Zn, particulalry in combination with an ionophore (such as HCQ), should be considered for randomized controlled trials (RCT) in patients with COVID‐19. It is through RCTs that these promising initial signals of zinc efficacy in COVID‐19 disease will ultimately be confirmed or disproven.

Vitamin E and respiratory tract infections in elderly nursing home residents: a randomized controlled trial


https://pubmed.ncbi.nlm.nih.gov/15315997/