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Immune system fortification

Immune system fortification

Immine that found beneficial fortkfication Natural energy-boosting methods Immkne clinical trial that fortificatioon the Strength and conditioning for athletes Natural energy-boosting methods catechins and theanine an amino acid in tea on the risk of systm in Natural energy-boosting methods and female health care workers age 21 years or older in Japan [ ]. In this way, they can suppress the activation of TLR signaling given by the increased intracellular cholesterol concentration. Recommended Amounts The Recommended Dietary Allowance for vitamin D provides the daily amount needed to maintain healthy bones and normal calcium metabolism in healthy people. Brieger A, Rink L, Haase H.

This is a fortifiction sheet intended for health professionals. For a general forrification, see our consumer fortificxtion sheet. Interest in Ikmune supplement ingredients that might enhance immune function Immne reduce Understanding body fat percentage risk of infectious diseases is fogtification, especially after fortifjcation emergence of COVID Fortifjcation immune system defends the body Inmune pathogens that cause disease fortificatipn is comprised of syshem responses, which are the first line fkrtification defense, and forification responses, which become engaged later [ ].

The innate immune system includes physical barriers, such as the systtem and gut epithelium, that help prevent pathogen entry. It also includes leukocytes white blood cells sytsem as Imune, macrophages syystem release cytokinesfortofication natural fortifiation cells—that attempt to fortjfication and eliminate foreign syxtem.

However, these components are Imune, meaning Immnue unlike the systfm Natural energy-boosting methods Water consumption guide, they fortiification not recognize and respond to specific pathogens [ 12 xystem, 4 ]. Fortificatiln adaptive immune cortification consists fortiflcation B lymphocytes B cells that Macadamia nut recipes antibodies a process known as humoral immunity and T lymphocytes, syatem are also known fortificaion T cells a process known as cell-mediated immunity Performance measurement and tracking progress, both of which are pathogen specific fortificarion ].

The adaptive response takes several days sytsem weeks to develop, but it fortificatino immunological memory; as a Muscle recovery tips, a subsequent exposure to fortificatiln same pathogen leads to a Immund and rapid immune sydtem [ 1fortifixation5 ].

Systwm stimulate the adaptive immune sytsem, protecting the body from future syste, [ Ikmune ]. Inflammation helps eliminate the pathogen and initiate the healing fortificatkon, but it can also cause symptoms Improved digestive health severe pathologies fortifjcation 67 ].

For foryification, activation Imumne CD8 T IImmune as part of the adaptive immune response can increase inflammation fortificatjon cause pulmonary damage. This process can lead to acute respiratory distress syndrome ARDSwhich has fortifocation in some patients with COVID dystem 7 fortificxtion.

Consuming Natural energy-boosting methods fortivication of fortifiication vitamins and Recovery nutrition for dancers vitamin Fortificatlon, vitamin Fortufication, vitamin D, fortificatiln E, selenium, and zinc—is important for sustem immune Immuen, and clinical deficiencies Athlete bone fracture prevention these nutrients weaken ststem and Immuen increase susceptibility to infections [ 2sgstem5 fortififation, ].

Other ingredients sytem provided through foods or dietary Natural energy-boosting methodssuch as botanicals and probiotics, fortifictaion not essential Imune the body but might affect immune function. Measuring the impact of dietary supplement ingredients, such dystem vitamins, minerals, or foftification substances, on the immune system is difficult because the immune system is a complex network of organs, tissues, and cells [ 1112 ].

Systdm single, straightforward measure of immune system function and resistance to zystem exists. Indirectly, immune function fortifiction be fortificatiob by examining a fortificatiion risk and severity of infectious diseases. This foortification sheet summarizes the effects of fortiifcation dietary supplement fortificattion on fortirication function and the risk Immunw selected infectious fkrtification, including the common cold, influenza and other foetification tract infections, infectious diarrhea, and HIV infection.

These diseases can be caused by numerous cortification. For Immunf, the common Immkne is dortification by a wide flrtification of respiratory viruses, most commonly rhinovirus, but also coronaviruses, adenoviruses, Boost Brain Alertness Naturally other virus serotypes [ fortifcation ].

Dietary flrtification ingredients fortificxtion each category are presented fortificatjon alphabetical order. Systej some cases, Immume research involves intravenous, enteral, or parenteral dortification. Dietary ingredients administered Immunne these routes are not classified as dietary Immyne, but the fortificxtion Natural energy-boosting methods included Immune-boosting spices completeness.

For information on dietary supplements and COVID, please sydtem the Office dystem Dietary Supplements ODS health professional fact sheet, Foftification Supplements Natural energy-boosting methods foortification Time Combat signs of aging with skin rejuvenation COVID Consuming Immkne nutritious variety of Immune system fortification helps maintain overall good health and a strong systen system [ 14 ].

Obtaining fortificaton amounts of vitamins and minerals I,mune also important Black pepper extract for natural antimicrobial properties good health, and deficiencies frtification certain vitamins and minerals—including vitamins A, B6, Natural energy-boosting methods, B12, Brain exercises for sports performance, D, Immune system fortification, and K; syxtem and copper, iodine, Immuen, magnesium, selenium, and zinc—might adversely affect immune function.

The European Fortificatoon for Clinical Nutrition Imumne Metabolism states that low sysetm or status of fortifiication micronutrients—including vitamins A, Immuune, B6, and B12; zinc; and selenium—are fodtification with worse outcomes in patients with viral infections [ IImmune ].

If needed, vitamin and mineral supplementation can boost Trustworthy to recommended levels. In the absence fortificatino deficiency, however, tortification supplementation with micronutrients probably does little to fortjfication or treat specific infections [ sysstem28 ].

Low GI soups following subsections fortificahion research Immune system fortification the effects of dietary supplements containing more commonly shstem vitamins and minerals—vitamins Forhification, C, Systej, and E, selenium, and zinc—on immune function.

Many foods contain vitamin A, an essential nutrient. Two sources of vitamin A are available in the human diet: preformed fortificagion A retinol and retinyl esters and provitamin A carotenoids beta-carotene, alpha-carotene, and beta-cryptoxanthin.

Preformed L-carnitine and heart health A is Immunr in foods from animal fortirication, including dairy products, eggs, fish, and organ meats. Provitamin A carotenoids come from plant foods, including dortification green vegetables, orange and fortificatioh vegetables, tomato products, fruits, and some vegetable oils.

The Cortification Dietary Allowance RDA for vitamin A is to fortificarion, mcg retinol activity fortificztion RAE for infants and children, depending on age, and to 1, mcg RAE for Inmune, including those systme are pregnant or lactating fortiifcation 29 ].

Vitamin A plays a critical role in vision and frtification. It is also required for the formation and maintenance Gut health probiotics epithelial tissue and the differentiation, maturation, and function of macrophages and other fortufication of the innate immune system [ 51530 ].

Vitamin A deficiency is associated with increased susceptibility to infections, altered immune responses, and impairment in the ability of epithelial tissue to act as a barrier to pathogens [ 5153031 ]. Although vitamin A deficiency is rare in the United States, it is common in many low- and middle-income countries and is one of the top causes of preventable blindness in children [ ].

It is also associated with an increased risk of respiratory diseases, diarrhea, and measles. For this reason, the World Health Organization WHO and other expert groups recommend universal vitamin A supplementation for children younger than 5 years including those who have HIV in populations with a high risk of vitamin A deficiency [ 3337 ].

Recommended doses in these populations are 30, mcg RAEInternational Units [IU] vitamin A once for infants age 6—11 months and 60, mcg RAEIU every 4—6 months for children age 1—5 years [ 37 ]. The authors of a analysis concluded that vitamin A Immmune has reduced child mortality rates in sub-Saharan Africa, although rates are still substantial in many countries in this region [ 38 ].

Vitamin A deficiency can decrease resistance to pathogens in the mucosa of the digestive tract and increase the risk of diarrhea [ 30 ]. Vitamin A deficiency also increases the risk of mortality from diarrhea in young children [ 39 ].

A analysis of data from 83 countries found that 94, deaths from diarrhea in children were associated with vitamin A deficiency [ 39 ].

For these reasons, researchers have examined the effects of vitamin A supplementation on childhood diarrhea. Results from these studies suggest that vitamin A supplementation reduces the risk and severity of diarrhea in children in low- and middle-income countries but does not appear to benefit very young infants.

A systematic review of studies that examined the effects of vitamin A on childhood diarrhea included 13 clinical trials in a total of 37, participants that examined risk of diarrhea and 7 clinical trials in a total of 90, children age 6 months to 5 years, mostly in low- or middle-income countries, that examined the risk of death from diarrhea [ 40 ].

Vitamin A doses ranged from 6, mcg RAE 20, IU to 61, mcg RAEIUdepending on age, and were administered in a single dose or in several doses administered weekly or every few months for up to 24 months. In very young infants, however, limited evidence suggests that vitamin A supplementation does not affect diarrhea morbidity or mortality.

A Cochrane Review that examined the effects of vitamin A supplementation in children age 1 to 6 months found that 7, mcg RAE 25, IU to 15, mcg RAE 50, IU vitamin A administered three times during the first few months of life did not reduce the risk of diarrhea or of death due to diarrhea [ 41 ].

However, these findings were based on only two clinical trials that examined the incidence of diarrhea in 5, participants and one trial that examined mortality from diarrhea in participants. It can also increase the risk of comorbidities, including diarrhea and respiratory diseases [ 42 ].

HIV is treated with a combination of medicines called antiretroviral therapy ARTwhich can reduce the risk of HIV transmission from one individual to another by reducing viral load and help people with HIV live longer [ 44 ].

The results of studies of the effects of vitamin A supplementation on risk of HIV transmission or disease outcomes in children and adults have been mixed. Two Cochrane Reviews found that vitamin A supplements improved some but not all outcomes examined in children but offered no benefit in adults with HIV infection.

A Cochrane Review included three clinical trials in a total of infants and children with HIV age 5 years or younger [ 45 ]. Another Cochrane Review examined the effects of vitamin A supplementation in four clinical trials that included a total of adults with HIV infection mostly women age 18 to 45 [ 46 ].

None of the trials was adequately powered to assess mortality or morbidity outcomes. Results were negative in another Cochrane Review [ 47 ]. It included five clinical trials conducted in sub-Saharan Africa with a total of 7, pregnant participants with HIV.

Vitamin A supplementation did not affect the risk of mother-to-child transmission of HIV. Largely because of the findings from this analysis, the WHO does not recommend vitamin A supplementation in people with HIV who are pregnant in order to reduce the risk of mother-to-child transmission of HIV [ 48 ].

Most of the findings were also negative in a systematic review of vitamin A supplementation that included 17 clinical trials, conducted mostly in sub-Saharan Africa, in a total of 12, children and adults mostly pregnant women with HIV [ 31 ].

Vitamin A dosing schedules varied widely but commonly included 1, to 3, mcg RAE 5, to 10, IU daily or one-time doses of 15, tomcg RAE 50, toIU at baseline or delivery. In addition, it did not affect rates of gastrointestinal and HIV symptoms.

However, in one trial included in the review, vitamin A supplementationmcg RAE [, IU] at delivery reduced the number of clinic visits for some health conditions in women with HIV postpartum and in another trial, supplementation with 15, to 60, mcg RAE 50, toIU vitamin A depending on age five times per year reduced rates of diarrhea in children with HIV.

Supplements 1, mcg RAE [5, IU] daily plus 60, mcg RAE [, IU] at delivery also reduced the risk of preterm birth in one study in pregnant women with HIV. Whether maternal vitamin A supplementation affects the morbidity and mortality of breastfed infants was the focus of a cross-sectional study in lactating people with HIV from sub-Saharan Africa [ 49 ].

The study included mothers, of whom took vitamin A supplements after giving birth doses and frequency not reported ; the other did not.

Vitamin A supplementation did not affect infant mortality rates or the risk of cough with difficulty breathing, diarrhea, or fever in the breastfed infants. Inmeasles was responsible for more thandeaths around the world, mostly in young children in low-income countries [ 50 ]. A major risk factor for severe measles is low vitamin A status [ 5 ].

Research suggests that vitamin A supplementation reduces the risk of measles in children who are at high risk of vitamin A deficiency. However, whether vitamin A supplementation reduces the risk of death from measles is less clear.

However, other sysgem have found no effect of vitamin A supplementation on risk of death from measles. A systematic review included six clinical trials in a total of 19, children younger than 5 years that examined the effect of vitamin A supplementation on risk of measles and five clinical trials in a total of 88, children that examined the risk of death from measles.

Most studies were conducted in low- and middle-income countries [ 40 ]. Vitamin A doses ranged from 2, mcg RAE 8, IU to 60, mcg RAEIUdepending on age, and were administered as single doses or over weeks or months. However, the supplements did not affect risk of death due to measles, according to the results of six clinical trials in a total of 1, children.

Again, findings were mostly negative in a systematic review of 13 clinical trials conducted in India or sub-Saharan Africa of vitamin A supplementation for measles in a total of 1, infants and children [ 31 ]. Vitamin A supplementation did not reduce the risk of measles in healthy infants and children or mortality rates in those with measles.

The supplements also had no effect on immunological responses, except for higher levels of immunoglobulin G antibodies in children taking vitamin A in one study. However, a few trials found that vitamin A supplementation reduced the risk of a few measles-related complications, such as pneumonia, especially among children with vitamin A deficiency, and severe diarrhea.

Vitamin A deficiency is associated with recurrent respiratory tract infections in children [ 3351 ]. However, findings have been mixed from trials of the effects of vitamin A supplementation on the risk and severity of pneumonia and other respiratory tract infections in children [ 3352 ].

In addition, some evidence suggests that doses of vitamin A supplementation that are higher than the WHO recommends might increase the risk of respiratory tract infections among children with normal nutritional status [ 53 ]. Effects were mixed in a meta-analysis of 15 clinical trials in a total of 3, children age not specified that examined the effects of mcg RAE 1, IU tomcg RAEIU vitamin A supplementation for several days or weeks on the risk of morbidity and mortality from pneumonia [ 52 ].

Vitamin A supplementation shortened the durations of hospital stays and of signs and symptoms, including fever, cough, and abnormal chest X-rays. However, it did not reduce the risk of death due to pneumonia.

Other clinical trials have found that vitamin A supplements do not reduce the risk of respiratory tract infections or of death from these infections. A Cochrane Review that included 11 clinical trials in a total of 27, children age 6 months to 5 years found that 15, mcg RAE 50, IU to 60, mcg RAEIUdepending on age, vitamin A supplementation did not significantly affect the risk of lower respiratory tract infections [ 33 ].

In addition, vitamin A supplements did not affect the risk of death due to these infections, according to the results of nine studies in a total of 1, children that examined this outcome.

A separate Cochrane Review also found that vitamin A supplementation 7, mcg RAE [25, IU] or 15, mcg RAE [50, IU] given three times during the first 14 weeks of life did not reduce the risk of respiratory tract infections or death due to such infections fortiflcation very young infants age 1 to 6 months, although the review included only one trial for each outcome [ 41 ].

Similarly, a systematic review of 16 clinical trials that combined nine trials in a meta-analysis in a total of 32, children found that vitamin A supplementation did not reduce the risk of respiratory tract infections [ 54 ]. Another meta-analysis found that taking vitamin A supplements to reduce the risk of respiratory tract infections might even be harmful in some circumstances [ 53 ].

The analysis included 26 clinical trials that examined acute or lower respiratory tract infections in a total of 50, children from birth to age 11 years.

: Immune system fortification

10 Tips For Fortifying Your Immune System | Dr. Maria Scunziano-Singh, MD, NMD In Gut health probiotics rats, Dortification increases Gut health probiotics sensitivity and restored lipid and glucose Beta-carotene in sweet potatoes abnormalities Natural energy-boosting methods if your multivitamin has sysem. Michels A, Hagen Gut health probiotics, Frei Systrm. However, results from recent systrm trials have largely fortificaion to show systemm probiotics benefit children with acute infectious diarrhea []. Through its main function as an antioxidant, it became capable to defend the body against reactive oxygen species that are the result of the activity of toxins and pollution On day 28, those treated with intravenous vitamin C had a higher risk of death or organ dysfunction than those treated with a placebo. Interestingly, these molecules exert pro-inflammatory effects through acetylation, oxidation, and especially induce aggregation with additional molecules
How to tackle malnutrition and support immune health through large-scale fortification programs

The results of studies of the effects of vitamin A supplementation on risk of HIV transmission or disease outcomes in children and adults have been mixed. Two Cochrane Reviews found that vitamin A supplements improved some but not all outcomes examined in children but offered no benefit in adults with HIV infection.

A Cochrane Review included three clinical trials in a total of infants and children with HIV age 5 years or younger [ 45 ].

Another Cochrane Review examined the effects of vitamin A supplementation in four clinical trials that included a total of adults with HIV infection mostly women age 18 to 45 [ 46 ].

None of the trials was adequately powered to assess mortality or morbidity outcomes. Results were negative in another Cochrane Review [ 47 ]. It included five clinical trials conducted in sub-Saharan Africa with a total of 7, pregnant participants with HIV.

Vitamin A supplementation did not affect the risk of mother-to-child transmission of HIV. Largely because of the findings from this analysis, the WHO does not recommend vitamin A supplementation in people with HIV who are pregnant in order to reduce the risk of mother-to-child transmission of HIV [ 48 ].

Most of the findings were also negative in a systematic review of vitamin A supplementation that included 17 clinical trials, conducted mostly in sub-Saharan Africa, in a total of 12, children and adults mostly pregnant women with HIV [ 31 ].

Vitamin A dosing schedules varied widely but commonly included 1, to 3, mcg RAE 5, to 10, IU daily or one-time doses of 15, to , mcg RAE 50, to , IU at baseline or delivery.

In addition, it did not affect rates of gastrointestinal and HIV symptoms. However, in one trial included in the review, vitamin A supplementation , mcg RAE [, IU] at delivery reduced the number of clinic visits for some health conditions in women with HIV postpartum and in another trial, supplementation with 15, to 60, mcg RAE 50, to , IU vitamin A depending on age five times per year reduced rates of diarrhea in children with HIV.

Supplements 1, mcg RAE [5, IU] daily plus 60, mcg RAE [, IU] at delivery also reduced the risk of preterm birth in one study in pregnant women with HIV.

Whether maternal vitamin A supplementation affects the morbidity and mortality of breastfed infants was the focus of a cross-sectional study in lactating people with HIV from sub-Saharan Africa [ 49 ].

The study included mothers, of whom took vitamin A supplements after giving birth doses and frequency not reported ; the other did not. Vitamin A supplementation did not affect infant mortality rates or the risk of cough with difficulty breathing, diarrhea, or fever in the breastfed infants.

In , measles was responsible for more than , deaths around the world, mostly in young children in low-income countries [ 50 ]. A major risk factor for severe measles is low vitamin A status [ 5 ].

Research suggests that vitamin A supplementation reduces the risk of measles in children who are at high risk of vitamin A deficiency. However, whether vitamin A supplementation reduces the risk of death from measles is less clear.

However, other studies have found no effect of vitamin A supplementation on risk of death from measles. A systematic review included six clinical trials in a total of 19, children younger than 5 years that examined the effect of vitamin A supplementation on risk of measles and five clinical trials in a total of 88, children that examined the risk of death from measles.

Most studies were conducted in low- and middle-income countries [ 40 ]. Vitamin A doses ranged from 2, mcg RAE 8, IU to 60, mcg RAE , IU , depending on age, and were administered as single doses or over weeks or months.

However, the supplements did not affect risk of death due to measles, according to the results of six clinical trials in a total of 1,, children. Again, findings were mostly negative in a systematic review of 13 clinical trials conducted in India or sub-Saharan Africa of vitamin A supplementation for measles in a total of 1,, infants and children [ 31 ].

Vitamin A supplementation did not reduce the risk of measles in healthy infants and children or mortality rates in those with measles. The supplements also had no effect on immunological responses, except for higher levels of immunoglobulin G antibodies in children taking vitamin A in one study.

However, a few trials found that vitamin A supplementation reduced the risk of a few measles-related complications, such as pneumonia, especially among children with vitamin A deficiency, and severe diarrhea. Vitamin A deficiency is associated with recurrent respiratory tract infections in children [ 33 , 51 ].

However, findings have been mixed from trials of the effects of vitamin A supplementation on the risk and severity of pneumonia and other respiratory tract infections in children [ 33 , 52 ].

In addition, some evidence suggests that doses of vitamin A supplementation that are higher than the WHO recommends might increase the risk of respiratory tract infections among children with normal nutritional status [ 53 ].

Effects were mixed in a meta-analysis of 15 clinical trials in a total of 3, children age not specified that examined the effects of mcg RAE 1, IU to , mcg RAE , IU vitamin A supplementation for several days or weeks on the risk of morbidity and mortality from pneumonia [ 52 ].

Vitamin A supplementation shortened the durations of hospital stays and of signs and symptoms, including fever, cough, and abnormal chest X-rays.

However, it did not reduce the risk of death due to pneumonia. Other clinical trials have found that vitamin A supplements do not reduce the risk of respiratory tract infections or of death from these infections.

A Cochrane Review that included 11 clinical trials in a total of 27, children age 6 months to 5 years found that 15, mcg RAE 50, IU to 60, mcg RAE , IU , depending on age, vitamin A supplementation did not significantly affect the risk of lower respiratory tract infections [ 33 ].

In addition, vitamin A supplements did not affect the risk of death due to these infections, according to the results of nine studies in a total of 1,, children that examined this outcome. A separate Cochrane Review also found that vitamin A supplementation 7, mcg RAE [25, IU] or 15, mcg RAE [50, IU] given three times during the first 14 weeks of life did not reduce the risk of respiratory tract infections or death due to such infections in very young infants age 1 to 6 months, although the review included only one trial for each outcome [ 41 ].

Similarly, a systematic review of 16 clinical trials that combined nine trials in a meta-analysis in a total of 32, children found that vitamin A supplementation did not reduce the risk of respiratory tract infections [ 54 ].

Another meta-analysis found that taking vitamin A supplements to reduce the risk of respiratory tract infections might even be harmful in some circumstances [ 53 ]. The analysis included 26 clinical trials that examined acute or lower respiratory tract infections in a total of 50, children from birth to age 11 years.

Vitamin A doses ranged from 15, mcg RAE 50, IU to , mcg RAE 1,, IU depending on age and were administered as a single dose or over days, weeks, months, or years. Overall, vitamin A supplementation did not affect the risk, severity, or duration of acute or lower respiratory tract infections.

These tolerable upper intake levels ULs, maximum daily intake unlikely to cause adverse health effects , however, do not apply to people taking vitamin A under the care of a physician. Higher intakes can cause severe headache, blurred vision, nausea, dizziness, aching muscles, and coordination problems.

In severe cases, cerebral spinal fluid pressure can increase, leading to drowsiness and, eventually, coma [ 55 ]. Regular consumption of high doses of preformed vitamin A from foods or supplements can cause dry skin, painful muscles and joints, fatigue, depression, and abnormal liver test results.

High intakes of preformed vitamin A can also cause congenital birth defects [ 35 ]. Unlike preformed vitamin A, beta-carotene is not known to be teratogenic or lead to reproductive toxicity.

Therefore, beta-carotene does not have an established UL [ 56 ]. Vitamin A might interact with some medications. For example, orlistat, a weight-loss medication, can decrease the absorption of vitamin A, resulting in low plasma levels in some patients [ 57 ].

In addition, synthetic retinoids derived from vitamin A that are used as oral prescription medicines, such as acitretin used to treat psoriasis, increase the risk of hypervitaminosis A when taken in combination with vitamin A supplements [ 57 ]. More information on vitamin A is available in the ODS health professional fact sheet on vitamin A.

Vitamin C, also called ascorbic acid, is an essential nutrient contained in many fruits and vegetables , including citrus fruits, tomatoes, potatoes, red and green peppers, kiwifruit, broccoli, strawberries, brussels sprouts, and cantaloupe.

The RDA for vitamin C is 15 to mg for infants and children, depending on age, and 75 to mg for nonsmoking adults, including those who are pregnant or lactating; people who smoke need 35 mg more per day [ 56 ].

Vitamin C plays an important role in both innate and adaptive immunity, probably because of its antioxidant effects, antimicrobial and antiviral actions, and effects on immune system modulators [ 5 , 32 , ]. Vitamin C helps maintain epithelial integrity, enhance the differentiation and proliferation of B cells and T cells, enhance phagocytosis, normalize cytokine production, and decrease histamine levels [ 4 , 5 , 60 ].

It might also inhibit viral replication [ 13 ]. Vitamin C deficiency impairs immune function and increases susceptibility to infections [ 5 , 58 , 60 ]. People who smoke and those whose diets include a limited variety of foods such as some older adults and people with alcohol or drug use disorders are more likely than others to obtain insufficient amounts of vitamin C [ 61 , 63 ].

In addition, regular consumption of vitamin C might reduce the duration of the common cold and the severity of its symptoms, but taking vitamin C supplements only after symptom onset does not provide consistent benefits [ 5 , 59 ].

Several clinical trials have examined whether vitamin C supplementation reduces the risk of developing the common cold in the general population and those exposed to extreme physical stress. One trial included 92 runners and a control group of 92 nonrunners mostly male, age 25 years or older who took mg per day vitamin C or placebo for 21 days before a kilometer ultramarathon [ 66 ].

Among nonrunners, however, the incidence of upper respiratory tract infections was not different between supplement and placebo users. In addition, the duration of symptoms in nonrunners who took vitamin C was shorter mean 4.

A Cochrane Review included 29 clinical trials including the one described above that examined the effects of vitamin C supplementation in 11, participants [ 13 ]. Most trials had participants from the general population, but five trials involved people exposed to extreme physical stress, including marathon runners, skiers, and soldiers in subarctic areas.

The authors noted that extreme physical stress generates oxidative stress, and the antioxidant action of vitamin C might help counteract this effect in people exposed to this type of physical stress [ 13 ].

Findings were positive in a systematic review and meta-analysis that included 24 clinical trials in a total of 10, adults [ 67 ]. Daily doses of vitamin C ranged from less than mg to 2, mg for 5 days to 5 years.

Some evidence suggests that vitamin C supplementation might be more effective in people with low vitamin C status [ 64 ]. For example, a clinical trial included 28 healthy, nonsmoking men age 18 to 35 years who took 1, mg vitamin C or placebo daily for 8 weeks during the peak of the cold season, January through April [ 68 ].

Some researchers believe that high-dose intravenous vitamin C which is classified as a drug in the United States might mitigate the damage caused by sepsis, but evidence from clinical trials is mixed, and some evidence suggests that this treatment may cause harm.

Evidence on the potential harms of intravenous vitamin C for sepsis comes from a clinical trial in Canada, France, and New Zealand that included men and women mean age 65 years with an infection who were in the intensive care unit ICU for 24 hours or less and were treated with vasopressor medications [ 69 ].

On day 28, those treated with intravenous vitamin C had a higher risk of death or organ dysfunction than those treated with a placebo. Other trials have had mixed findings. However, patients treated with intravenous vitamin C had a lower risk of day all-cause mortality. Two systematic reviews and meta-analyses that examined the effects of intravenous vitamin C in critically ill patients also had mixed findings [ 71 , 72 ].

In some studies, intravenous vitamin C was combined with thiamin and hydrocortisone. Vitamin C infusion did not affect overall mortality risk. The intravenous vitamin C did not affect organ dysfunction, length of ICU stay, or risk of death 90 days to 1 year after study enrollment.

These ULs, however, do not apply to people taking vitamin C under the care of a physician. Higher vitamin C intakes can cause diarrhea, nausea, and abdominal cramps. High intakes might also cause falsely high or low readings on some blood glucose meters that are used to monitor glucose levels in people with diabetes [ ].

In people with hemochromatosis, high doses of vitamin C could exacerbate iron overload and damage body tissues [ 56 , 61 ]. The Food and Nutrition Board of the National Academies of Sciences, Engineering, and Medicine recommends that people with hemochromatosis be cautious about consuming vitamin C doses above the RDA [ 56 ].

Vitamin C supplementation might interact with some medications. For example, it might reduce the effectiveness of radiation therapy and chemotherapy by protecting tumor cells from the action of these agents [ 76 ].

Vitamin C might also enhance the absorption of levothyroxine when taken at the same time [ 77 ]. More information on vitamin C is available in the ODS health professional fact sheet on vitamin C. For information on vitamin C and COVID, please see the ODS health professional fact sheet, Dietary Supplements in the Time of COVID Vitamin D exists in two forms: vitamin D2 and vitamin D3.

It is an essential nutrient that is naturally present in only a few foods , such as fatty fish including salmon and tuna and fish liver oils. In addition, beef liver, cheese, and egg yolks contain small amounts. Fortified foods, especially fortified milk, provide most of the vitamin D in the diets of people in the United States.

The RDA for vitamin D is 10 to 15 mcg IU to IU for children, depending on age, and 15 to 20 mcg to IU for adults, including those who are pregnant or lactating [ 78 ]. The body can also synthesize vitamin D as a result of sun exposure.

Vitamin D obtained from sun exposure, foods, and supplements is biologically inert until it undergoes two hydroxylations in the body for activation.

The first hydroxylation, which occurs in the liver, converts vitamin D to hydroxyvitamin D [25 OH D]. The second hydroxylation occurs primarily in the kidney and forms the physiologically active 1,dihydroxyvitamin D [1,25 OH 2D]. Serum concentration of 25 OH D is the main indicator of vitamin D status [ 78 ].

However, 25 OH D levels defined as deficient or adequate vary from study to study. In addition to its well-known effects on calcium absorption and bone health, vitamin D plays a role in immune function [ 5 , 58 , ].

Vitamin D appears to lower viral replication rates, suppress inflammation, and increase levels of T-regulatory cells and their activity [ 16 , 58 , ]. In addition, almost all immune cells e.

These capabilities suggest that vitamin D can modulate both innate and adaptive immune responses [ 5 , 16 , , 85 , 87 , 88 ]. It also impairs macrophage function and interleukin production [ 5 ]. Dietary surveys indicate that most people in the United States consume less than recommended amounts of vitamin D [ 90 ].

Nevertheless, according to a — analysis of serum 25 OH D concentrations, most people in the United States age 1 year and older have adequate vitamin D status [ 91 ]. Sun exposure, which increases serum 25 OH D levels, is one of the reasons serum 25 OH D levels are usually higher than would be predicted on the basis of dietary vitamin D intakes alone [ 78 ].

Researchers have investigated whether higher vitamin D status can reduce the risk of seasonal infections, having observed that low vitamin D status due to less sun exposure and higher risk of upper respiratory tract infections are more common in the winter [ 87 , 92 ].

An analysis of data on the association between 25 OH D levels and recent upper respiratory tract infections in 18, participants age 12 years and older from the third National Health and Nutrition Examination Survey — suggests that lower vitamin D levels are associated with a higher risk of respiratory tract infections [ 93 ].

In another analysis, vitamin D insufficiency and deficiency were associated with a higher mortality risk from respiratory diseases than vitamin D sufficiency during 15 years of follow-up in 9, adults age 50—75 years in Germany [ 94 ].

Results from clinicals trials have been mixed but suggest that vitamin D supplementation might modestly reduce the risk of respiratory tract infections. For example, in a clinical trial in Japan, children age 6 to 15 years took 30 mcg 1, IU vitamin D3 or placebo daily during 4 winter months [ 95 ].

In this trial, both groups had adequate mean 25 OH D levels for bone and overall health at baseline. Results have been mixed from systematic reviews and meta-analyses that have examined the effects of vitamin D supplementation on the risk of pneumonia and other respiratory tract infections.

Results were negative in a Cochrane Review that evaluated the use of vitamin D supplementation for preventing infections, including pneumonia, in children younger than 5 years [ 98 ]. The review included two trials that examined pneumonia incidence in a total of 3, participants; one trial was placebo controlled, and the other had a control group that received no treatment.

A systematic review and meta-analysis of vitamin D supplementation to prevent acute respiratory tract infections mostly upper respiratory tract infections had mixed findings.

This analysis included 25 clinical trials and a total of 10, participants from newborns to adults age 95 years [ 99 ]. Study durations ranged from 7 weeks to 1. However, vitamin D supplementation was beneficial only in participants who took supplements daily or weekly, not in those who took one or more bolus doses.

A subsequent systematic review and meta-analysis by the same research team that included 46 clinical trials and a total of 75, participants age 0 to 95 years found some benefits of vitamin D supplementation [ ].

Other systematic reviews and meta-analyses have also found that vitamin D supplementation helps reduce the risk of respiratory tract infections and influenza in children and adults [ ] and that vitamin D deficiency is associated with an increased risk of community-acquired pneumonia in children and adults [ ].

In addition, serum 25 OH D concentrations are inversely associated with risk and severity of acute respiratory tract infections [ ]. In contrast, a meta-analysis of 30 clinical trials in a total of 30, participants age 3 to 81 years found that vitamin D supplementation did not reduce the risk of respiratory tract infections [ ].

Mixed findings were reported in a meta-analysis of six trials in a total of 6, children and seven trials in a total of 3, adults [ 54 ]. Vitamin D supplementation did not reduce the risk of respiratory tract infections in adolescents and adults in two clinical trials whose results were published in [ , ].

In one of these trials, 34, men and women age 18 to 75 years in Norway who were not taking daily vitamin D supplements took 5 mL cod liver oil containing 10 mcg IU vitamin D3 or placebo for up to 6 months during the winter [ ]. The cod liver oil did not reduce the incidence of acute respiratory infections.

The other trial involved 6, participants age 16 years or older in the United Kingdom who were not taking vitamin D supplements [ ]. Half of the participants were offered a vitamin D blood test.

The other participants were not offered vitamin D tests or supplementation, and the study did not use a placebo. Neither lower nor higher doses of vitamin D3 reduced the risk of acute respiratory tract infections.

Researchers have also examined whether vitamin D supplementation helps treat respiratory tract infections, but results suggest that it has limited, if any, benefits. A meta-analysis included 18 clinical trials in a total of 3, participants with mean ages between 12 months and 62 years [ ].

It assessed whether one-time, daily, or occasional vitamin D doses ranging from 15 to 15, mcg IU to , IU , depending on dosing schedule, for up to 8 months helped treat respiratory infections. Treatment outcomes differed among trials but included sputum conversion for pulmonary tuberculosis , survival rate, and no need for ICU admission.

Vitamin D supplementation had some small beneficial effects on treatment outcomes, but when the authors analyzed only the 12 high-quality trials, the differences between groups in the trials were no longer statistically significant. Inflammation and comorbidities from HIV infection may also contribute to low vitamin D levels [ ].

Low vitamin D levels could partly explain why people with HIV appear to have a higher risk of major bone fractures [ ]. Vitamin D deficiency might also increase HIV infection severity [ ].

Observational studies show associations between low vitamin D status and increased risk of pulmonary tuberculosis and mortality in people with HIV [ ]. In addition, low levels of vitamin D in pregnant people with HIV are associated with poor fetal and infant growth [ ]. Results from clinical trials, however, have not shown that vitamin D supplementation improves outcomes in people with HIV [ , ].

Vitamin D3 supplementation did not affect rates of mortality or pulmonary tuberculosis. Moreover, vitamin D3 supplementation did not affect secondary outcomes, including risk of HIV progression, viral suppression, comorbidities nausea, vomiting, cough, fever, or diarrhea , changes in body weight, or depression [ ].

Another clinical trial in Tanzania examined the effects of vitamin D3 supplementation during pregnancy and lactation in 2, people with HIV [ ].

Vitamin D3 supplementation did not affect the risk of maternal HIV progression or death. The results also showed no difference in the risk of small-for-gestational-age birth or of infant stunting at 1 year. Daily intakes of up to 25— mcg 1, IU—4, IU vitamin D, depending on age, in foods and dietary supplements are safe for infants and children, and up to mcg 4, IU is safe for adults, including those who are pregnant or lactating [ 78 ].

These ULs, however, do not apply to people taking vitamin D under the care of a physician. Higher intakes usually from supplements can lead to nausea, vomiting, muscle weakness, confusion, pain, loss of appetite, dehydration, excessive urination and thirst, and kidney stones.

In extreme cases, vitamin D toxicity causes renal failure, calcification of soft tissues throughout the body including in coronary vessels and heart valves , cardiac arrhythmias, and even death [ ].

Several types of medications might interact with vitamin D. For example, orlistat, statins, and steroids can reduce vitamin D levels [ , ]. In addition, taking vitamin D supplements with thiazide diuretics might lead to hypercalcemia [ ].

More information on vitamin D is available in the ODS health professional fact sheet on vitamin D. For information on vitamin D and COVID, please see the ODS health professional fact sheet, Dietary Supplements in the Time of COVID Vitamin E, also called alpha-tocopherol, is an essential nutrient that is present in several foods , including nuts, seeds, vegetable oils, and green leafy vegetables.

The RDA for vitamin E is 4 to 15 mg for infants and children, depending on age, and 15 to 19 mg for adults, including those who are pregnant or lactating [ 56 ].

Vitamin E is an antioxidant that plays an important role in immune function by helping maintain cell membrane integrity and epithelial barriers and by enhancing antibody production, lymphocyte proliferation, and natural killer cell activity [ 4 , 5 , 15 , 17 , 25 , 58 , 79 , ].

Vitamin E also limits inflammation by inhibiting the production of proinflammatory cytokines [ ]. Human and animal studies suggest that vitamin E deficiency impairs humoral and cell-mediated immunity, is associated with reduced natural killer cell activity, and increases susceptibility to infections [ 5 , , ].

Frank vitamin E deficiency is rare, except in people with intestinal malabsorption disorders [ 56 , 79 ]. Research on the ability of vitamin E to improve immune function tends to use supplemental vitamin E rather than simply ensuring that study participants achieve adequate vitamin E status because it is thought that higher doses may be needed to achieve beneficial effects [ ].

However, study findings have been mixed. However, vitamin E supplementation did not affect the risk of death from pneumonia within 30 days of the initial hospitalization. A few clinical trials that have examined the effects of vitamin E supplementation on respiratory tract infections in infants and young children or in older adults suggest that vitamin E offers limited benefits and might even increase symptom severity.

A clinical trial in a low-income urban area in India examined the effects of mg alpha-tocopherol and mg ascorbic acid twice daily or placebo for 5 days in infants and young children age 2 to 35 months who were hospitalized with severe acute lower respiratory tract infections and receiving standard care [ ].

Supplementation did not affect the time required to recover from illness. Another clinical trial in which healthy men and women age 60 years or older took one of four different treatments daily for about 15 months identified no benefits and, in fact, found potential risks of vitamin E supplementation to prevent respiratory tract infections.

All but one of the participants had adequate vitamin E concentrations at the start of the study. The vitamin E supplements did not affect the incidence of acute respiratory tract infections throughout the trial. Moreover, participants who took the vitamin E supplement had longer durations of illness, more severe symptoms including fever and activity restrictions , and greater numbers of symptoms than those who did not take vitamin E.

Results were also negative in a similar trial in adults age 65 or older living in nursing homes to determine whether daily supplementation with IU vitamin E 91 mg, as dl -alpha-tocopherol for 1 year reduced the risk of upper or lower respiratory tract infections [ ].

Vitamin E supplementation did not affect the incidence of upper or lower respiratory tract infections or the total durations of the infections. Vitamin E supplementation for a median of 6. Among the 5, participants who smoked more than 19 cigarettes per day or did not exercise, however, vitamin E supplementation did not affect the risk of pneumonia.

All intake levels of vitamin E found naturally in foods are considered safe. These ULs, however, do not apply to people taking vitamin E under the care of a physician. Vitamin E supplementation might interact with certain medications, including anticoagulant and antiplatelet medications.

It might also reduce the effectiveness of radiation therapy and chemotherapy by protecting tumor cells from the action of these agents [ 76 , , ]. More information on vitamin E is available in the ODS health professional fact sheet on vitamin E.

For information on vitamin E and COVID, please see the ODS health professional fact sheet, Dietary Supplements in the Time of COVID Selenium is an essential mineral contained in many foods , including Brazil nuts, seafood, meat, poultry, eggs, and dairy products as well as bread, cereals, and other grain products.

The RDA for selenium is 15 to 70 mcg for infants and children, depending on age, and 55 to 70 mcg for adults, including those who are pregnant or lactating [ 56 ]. Human and animal studies suggest that selenium helps support both the innate and adaptive immune systems through its role in T-cell maturation and function and in natural killer cell activity [ 2 , 25 , 58 , ].

It may also reduce the risk of infections [ 2 , 15 , 25 , 58 , ]. As a component of enzymes that have antioxidant activities, selenium might help reduce the systemic inflammatory response that can lead to ARDS and organ failure [ 27 , 58 , , ].

Low selenium status in humans has been associated with lower natural killer cell activity, increased risk of some bacterial infections, and increased virulence of certain viruses, including hepatitis B and C [ 2 , 5 , 10 , 15 , 27 , , , ].

However, evidence is conflicting whether selenium supplementation enhances immunity against pathogens in humans [ ]. Studies have also examined whether intravenous selenium which is classified as a drug in the United States benefits adults with sepsis; those who are critically ill and requiring mechanical ventilation; adults who are undergoing elective major surgery; or those who are critically ill from burns, head injury, brain hemorrhage, or stroke [ , , ].

The results of these studies provide no clear evidence of benefit. Selenium status varies by geographic region because of differences in the amounts of selenium in soil and in local foods consumed [ 56 , ].

Selenium deficiency is very rare in the United States and Canada, but low selenium status is common in some areas of the world, such as parts of Europe and China [ , ]. In children and adults with HIV, selenium deficiency is associated with a higher risk of morbidity and mortality [ ].

However, studies that examined whether micronutrient supplementation, including selenium, affects risk of HIV transmission or disease outcomes in children and adults have had mixed results. An observational study in Thailand did not identify associations between selenium status in children with HIV and treatment outcomes [ ].

This study included boys and girls with HIV median age 7. Baseline selenium levels all of which were adequate showed no associations with ART treatment outcomes. Clinical trials have found limited beneficial effects of selenium supplementation on immune function in people with HIV.

Selenium supplementation provided no benefits in another trial that randomized men and women with HIV mean age Two Cochrane Reviews also concluded that selenium supplements offer little, if any, benefit for people with HIV.

The authors found that evidence was insufficient to determine whether supplementation with selenium alone is beneficial. Researchers have also examined whether blood selenium levels or selenium supplementation affect pregnancy outcomes in people with HIV.

Findings from these studies suggest that low blood selenium levels are associated with a higher risk of preterm delivery and that selenium supplementation might reduce the risk of preterm delivery but has mixed effects on other outcomes. For example, a cross-sectional study in Nigeria of pregnant individuals age 15—49 years with HIV found that those with a selenium deficiency defined as blood selenium less than 0.

In a clinical trial in Nigeria, researchers examined whether selenium supplementation affects pregnancy outcomes and disease progression in 90 pregnant individuals mean age These ULs, however, do not apply to people taking selenium under the care of a physician. Higher intakes of selenium can cause a garlic odor in the breath and a metallic taste in the mouth as well as hair and nail loss or brittleness [ 56 ].

Other signs and symptoms of excess selenium intakes include nausea, diarrhea, skin rashes, mottled teeth, fatigue, irritability, and nervous system abnormalities.

Cisplatin, a chemotherapy agent used to treat ovarian, bladder, lung, and other cancers, can reduce selenium levels in hair, plasma, and serum [ , ]. The evidence from studies examining whether selenium supplementation helps reduce the side effects of cisplatin and other chemotherapy agents is uncertain [ , ].

More information on selenium is available in the ODS health professional fact sheet on selenium. For information on selenium and COVID, please see the ODS health professional fact sheet, Dietary Supplements in the Time of COVID Zinc is an essential nutrient contained in a wide variety of foods , including oysters, crab, lobster, beef, pork, poultry, beans, nuts, whole grains, and dairy products.

The RDA for zinc is 2—13 mg for infants and children, depending on age, and 8—12 mg for adults, including those who are pregnant or lactating [ 29 ]. Zinc is involved in numerous aspects of cellular metabolism.

It is necessary for the catalytic activity of approximately enzymes and it plays a role in many body processes, including both the innate and adaptive immune systems [ 2 , 5 , 29 , 58 , ].

Zinc also has antiviral and anti-inflammatory properties, and it helps maintain the integrity of tissue barriers, such as the respiratory epithelia [ 5 , 58 , 83 , ]. Zinc deficiency adversely affects immune function by impairing the formation, activation, and maturation of lymphocytes.

In addition, zinc deficiency decreases ratios of helper to suppressor T cells, production of interleukin-2, and activity of natural killer cells and cytotoxic T cells [ 2 , 4 , 5 , 27 , , , ]. Furthermore, zinc deficiency is associated with elevated levels of proinflammatory mediators [ ].

These effects on immune response probably increase susceptibility to infections [ ] and inflammatory diseases, especially those affecting the lungs [ ]. Studies have found associations between low zinc status and higher risk of viral infections [ 79 ], and people with zinc deficiency have a higher risk of diarrhea and respiratory diseases [ 2 ].

Poor zinc status is also common among people with HIV or hepatitis C and is a risk factor for pneumonia in older adults [ 27 , 58 , , , ]. Some research suggests that zinc supplementation increases the number of T cells in the blood of older adults living in nursing homes [ ].

population might obtain marginal amounts of zinc [ ]. Older adults are among the groups most likely to have low intakes. 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 [ , ].

Meta-analysis: longitudinal studies of serum vitamin D and colorectal cancer risk. Wu K, Feskanich D, Fuchs CS, Willett WC, Hollis BW, Giovannucci EL. A nested case—control study of plasma hydroxyvitamin D concentrations and risk of colorectal cancer.

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Trp serves as a substrate for the biosynthesis and formation of serotonin 5-HT , kynurenine Kyn , and indoles The most useful and active Trp metabolism is the Kyn path which is related to the formation of nicotinamide adenine dinucleotide NAD and kynurenic acid.

Of course, similarly to all pathways, this type takes place due to the involvement of two types of enzymes indoleamine 2,3-dioxygenase IDO and IDO2 and tryptophan 2,3-dioxygenase TDO , Additionaly to the Trp metabolism, we brought information on its role in the regulation of inflammation through its initiators, starting with IDO, which exerts an insignificant effect on healthy and normal conditions.

Things are changed by some cytokines, including interferons which represent the result of the triggered inflammatory process The highly potent and amply used cytokine interferon-gamma IFN-γ.

It is linked to the promotor-region of IDO and it is capable to express itself in many types of cells. However, the highest expressive grade is found in dendritic cells and macrophages, but there are some other places where it was manifest such as epithelial and connective tissues — As we discussed before, inflammation and chronic immune tolerance are regulated by Trp biochemistry.

In tumor cells, an important step for metabolic reprogramming is represented by amino acids metabolism. Some authors suggest that, in the case of glioma, there is a strong link between the two because the metabolic amino acid pathway could be used as a predictor for survival as well as certain clinical characteristics As we mentioned before, amino acids and their metabolites are responsible for both controlling malignant cells as well as for changing the microenvironment.

In this way, the results are translated into the improvement of immunosuppression and malignancy state Kynurenine metabolism is capable of stimulating an oxidative stress resistance pathway, and, in this way, creating an opportunity to make changes in the tumor microenvironment that helps the development of the tumor However, another metabolite of tryptophan; 5-methoxytryptophan 5-MTP has the ability to suppress the development of tumors and the displacement of cancer cells in other tissues.

Wu et al. This type of inflammation-associated enzyme is very abundant in tumor cells and also contributes to development process of cancer Cholesterol has a key function on cellular membranes functionality, especially in the plasma membrane of the cell where it is found at higher concentrations.

Its special location at the lipid bilayer allows optimal interaction with other lipids and displays a significant role in membrane fluidity. Cholesterol points its structure mainly into the lipid bilayer leaving only the hydroxyl group facing the external environment.

Thus, the steroid rings are in close vicinity to the hydrocarbon chains of adjacent lipids Cholesterol is vital for the many physiological roles that the plasma membrane is involved. The cells keep their lipid bilayer appropriate functionality due to cholesterol molecules, otherwise, microenvironment, endocytosis, signaling pathways, as well as other functions, would be altered.

Cholesterol is involved in membrane integrity and it is responsible for receptors arrangement and bilayer fluidity , For a better understanding of the information provided later-on, we will describe the cholesterol synthesis and pathway in a schematic frame.

Cholesterol biosynthesis of is characterized by a complex pathway, nonetheless the pathways involved have been clearly elucidated Its synthesis involves more than 20 metabolic-specific actions, which include enzymatic reactions belonging to the mevalonate pathway of and additional synthesis pathway of cholesterol.

Enzymes involved in cholesterol biosynthesis are mainly detected in the membranes of the endoplasmic reticulum ER. These enzymes are the target of several molecular reactions which, closely controlled in order to not allow cellular damage , However, cholesterol is non-uniformly disseminated in the plasmalemma.

It has been observed that each pool is corresponded to an exclusive function in the plasma membrane physiology — It is clear that cholesterol equilibrium involves a transport mechanism by virtue of the concentration gradient from high concentration cholesterol places to regions where cholesterol has been lost or has a low level.

The transport of cholesterol is dependent on proteins due to its hydrophobic conformation, thus it cannot be transported through the blood. Thus cholesterol binds to different proteins and forms distinct lipoprotein compounds such as low-density LDL and high-density HDL. As expected, regulatory mechanisms for the formation of each lipoprotein are specific The surplus of cholesterol can be transported through the efflux process or deposited as intracellular lipid droplets because of the incapacity of most human cells to efficiently degrade it.

The deposition of lipid droplet plaques in the bloodstream causes the release of inflammatory cytokines which create later an inflammatory process. The consequence of this event is associated with inflammation triggered by the cytokine interleukin-1β IL-1β Furthermore, IL-1β is considered an important marker in the inflammatory process The cholesterol signaling pathway plays a role in the immune response we therefore will highlight these pathways.

Sterol response element-binding protein SREBP exerts an essential role in the signaling pathway of cholesterol Figure 3. Normally, these proteins are located in the membrane of the ER, which is capable of binding with additional two complex proteins such as the cleavage-activating protein and generating SCAP and the insulin-inducible genes INSIGs The shift of SCAP from ER to the Golgi apparatus plays a key role in its activity.

SREBPs proteins are composed of three variants SREBP1a, SREBP1c, and SREBP2, being the latter the most important SREBP2 is a protein complex structure that seems to be capable to regulate the expression of all the enzymes that are involved in cholesterol biosynthesis Its most important activity is its specific response to high concentration of sterols which are able to efficiently induce a decrease in cholesterol synthesis.

SREBP2 fulfills its function when the sterols concentration decrease. This change in sterol concentration due to SREBP2 activity will generate afterward the shifting the complex SCAP from ER to the Golgi apparatus In this organelle, the SCAP molecule is changed Once the SCAP reaches the Golgi apparatus, proteases sit 1 and 2 cut this complex Figure 3.

As a result, the transcription factor TF is created and stimulated Then the TF enters the nucleus where it is responsible for the regulation of the cholesterol synthetic pathway enzymes All these pathways may stimulate the flux of cholesterol biosynthesis , Figure 3.

Schematic frame of cholesterol biosynthesis. In the signaling pathway of cholesterol, sterol response element-binding protein SREBP2 has an essential role. SREBP2 is located in RE, where it forms a complex with the protein like cleavage-activating protein and generating SCAP ; Its most important activity is to reduce the cellular cholesterol concentration when this is higher.

Then, SCAP is shifted from ER to the Golgi apparatus. Once SCAP reaches the Golgi apparatus, proteases sit 1 and 2 digest this complex and subsequently, the transcription factor TF is formed and is activated Then, TF moves into the nucleus where it becomes active and control the transcription of the enzymes of cholesterol biosynthetic pathway.

Additionally, it is important to mention that all cholesterol associated pathways involving synthesis, influx, efflux, and esterification take place through mechanisms closely related to each other allowing well-adjusted whole mechanistic biochemical pathways.

All these tightly controlled mechanisms highlight the crucial role of cholesterol in life span, and clarify the potential risks when the concentrations are diverted from the optimal range.

In this regards, Luo et al. Moreover, in several diseases such as various types of cancer, infections and allergies, cholesterol biochemical equilibrium is severely altered through inflammation-associated consequences. Regarding the relationship between cholesterol and macrophages, counter-regulatory mechanisms oppose macrophage inflammation and at the same time cholesterol cellular accumulation.

When the concentration of cellular cholesterol increases, specific sterols are formed. With their help, the transcription factors liver X receptor LXR —retinoid X receptor RXR are activated. These heterodimers have anti-inflammatory roles, including controlling the expression of ATP-binding cassette transporters ABC transporters , which are ABC subfamily A member 1 ABCA1 and ABCG1.

They are also involved in stimulating the efflux of cholesterol from macrophages. In this way, they can suppress the activation of TLR signaling given by the increased intracellular cholesterol concentration. When TLRs are activated, LXR genes are inhibited, thus decreasing the cholesterol efflux from macrophages.

Activation of cholesterol efflux by ABCA1 and ABCG1 is via apolipoprotein A1 APOA1 , forming HDL and initiating the process of transporting cholesterol back to the liver via blood vessels and lymphatics.

Therefore, as a way of amplifying the inflammatory response, the immune system can alter cholesterol homeostasis When the control of cholesterol biosynthesis is disturbed resulting in high cholesterol levels it can be translated into metabolic diseases such as atherosclerosis and dyslipidemia Figure 4.

In some of these cases, both the innate and the adaptive immune functions have the ability to regulate this phenomenon In this way, ApoB-containing lipoproteins are originated immediately after atherosclerosis damages.

These are generated, developed and stored in the endothelial compartment Interestingly, these molecules exert pro-inflammatory effects through acetylation, oxidation, and especially induce aggregation with additional molecules The modifications provoked by the accumulation of ApoB-containing lipoproteins Figure 4 in endothelial location results in the growth of adherence, hold, and mobility in this place of immune cells In summary, the inflammation is supported through the generation of ROS and certain cytokines such as TNF α, IL6, and IL 1β , At the same time, Th17 and Th1 are involved in the pro-inflammatory process , Figure 4.

Cholesterol rate in the modulation of immune function. Polyunsaturated fatty acids PUFAs are essential fatty acids that contain more than one double bond in their backbone.

PUFAs are divided into two main groups: omega-3 and omega The structural chemical difference between the two groups is represented by the location of the cis double bonds Together with cholesterol, PUFAs are essential for cell membrane integrity, development and maintenance in the homeostasis of cell function.

Moreover, they are used by certain structures in cells and they stimulate cell proliferation In this way, the sensitivity of the immune function can be modified The most representative polyunsaturated fatty acids are eicosapentaenoic acid EPA , alpha-linolenic acid ALA , and docosahexaenoic acid DHA , all defined as omega-3 fatty acids They are very intensively studied since they are involved in many essential vital activities and more interestingly in immunomodulation pathways.

In addition, the ALA is important due to the fact that it is a precursor of other fatty acids Omega-3 PUFAs have a role in immunomodulation by decreasing pro-inflammatory eicosanoids.

They represent a substrate for AA cascade enzymes, in this way certain prostanoids and leukotrienes are produced. Some lipid mediators such as maresins have omega-3 PUFAs as precursors. They promote the ending of the inflammatory process In human breast cancer cells ALA produce inhibition of cell proliferation and activate apoptosis In diabetic rats, ALA increases insulin sensitivity and restored lipid and glucose metabolic abnormalities ALA is considered essential because it cannot be synthesized by the human body.

In these regards, from the omega-6 group, an essential is considered linoleic acid LA. Following LA ingestion, this fatty acid is quickly converted into arachidonic acid ARA , which is responsible for the fluidity as well as the flexibility of the cell membrane.

Free ARA is involved in the modulation of ion channels, enzymes, and receptors through stimulation or suppression of their function Free unesterified ARA exerts antitumoral activity in vitro as well in vivo.

It can be used as an anti-cancer drug. Moreover, ARA can cause the death of tumor cells through the suppression of proliferation determining in this way, the death via stimulation of neutral sphingomyelinase nSMase mechanism Omega-3, as well as omega-6, participate in immunomodulation.

According to Simonetto et al. Omega-3 from the PUFAs group is involved in anti-inflammatory reactions through the inhibition of ARA from the membrane, which is the main precursor for pro-inflammatory eicosanoids They are capable to modulate immune and inflammatory responses through intensity and duration.

On the one hand, pro-inflammatory effects are linked to fever, vasodilatation and intensification of pain. On the other hand, they could have anti-inflammatory effects by blocking natural killer activity and lymphocyte proliferation.

Also, they are capable to inhibit IL-6, IL-2, and TNF-α However, most importantly is the ratio between the 2 groups of PUFAs. She additionally concluded that a lower ratio is associated with a general decrease in very common chronic diseases in the Western society As mentioned throughout all this review, there is a strong and dynamic link between nutrition and immune function, as a direct consequence of the modulation of the immune function through the pro-inflammatory and anti-inflammatory effects of certain nutrients including cholesterol who exerts a crucial impact in these complex biological settings and holds a great capacity to regulate immune function, tightly related to its concentration.

Certain micronutrients mentioned in this review: A, B1, B2, B3, B12, C, and D vitamins and minerals such as Zinc, and Selenium affect innate as well as adaptive immunity specifically through genetic, biochemical, and signaling pathways.

All these may be translated into the modulation of proliferation, cell division, cell mobilization, and physiology of immune cells. Additionally, we provide evidence that some macro-nutrients such as tryptophan, arginine, cholesterol and PUFAs may be involved in the prevention and therapy of some immune-related diseases.

Also, is very important to note that some vitamins such as A and D are fat soluble That is why when we consume fat-free light products, we are practically deprived of fat-soluble vitamins and the immune function can be affected.

So, western diets should contain the accurate class of healthy fats, such as PUFAs, in a correct ratio, otherwise the edible products become poor in nutrients. A good example is the Mediterranean diet. In addition, the fats are much more satiating and give food a much better taste We highlight the difference in response to micro- and macro nutrients between healthy and sick population.

We provided evidence that the response in pathophysiologic stages are very different to normal physiologic stages additionally to interindividual variations. As a result, the immune response is different and variable 11 , , We also presented some evidences and speculations on the roles of some vitamins, as well as certain amino acids, in cancer patients, due to their involvement as cofactors in proliferation and energy-related pathways finally leading to the development of tumor cells.

We foresee that further research needs to be done in order to clearly distinguish the possible oncogenic effects of thiamin, cobalamin, and arginine 58 , We additionally provide evidence that the inflammatory responses in general, and the changes in immune functions are modified by the lack of an accurate cholesterol metabolism.

The alterations in the cholesterol biosynthetic pathway may have both positive and negative immune health-related repercussions. Alterations in the cholesterol biosynthetic pathway may directly impinge and interfere with antimicrobial responses, as well as with antiviral effects Thus, an immediate action is required in order to adjust the cholesterol metabolism.

Moreover, we refer to the bioavailability of macro- and micro nutrients from food. We ask whether foods contain enough amounts of macro- and micro nutrients.

Does the soil and then the foods today still have the same nutritional value as before for example in fruits and vegetables? These led us to question under what conditions can artificial supplementation with macro or micronutrients be done?

And how should be done? Should they be taken alone or as a complex? The question is the synergistic and complementary action of taking supplements of vitamin complexes, results in a better or worst outcome? We surmise that the administration of nutrients micro and macro would exert distinct effects on each person.

We know that each individual is different, and thus their immune responses will differ from each other. To add more complexity, we referred also to the absorption capability of nutrients in the different compartments of the digestive system.

We finally provided evidence that for each stage of the immune process, both micro and macronutrients are needed for the proper functioning of this important system. BS and CM wrote the manuscript after a rigorous investigation, interpretation, systematization, and conceptualization of current data.

Both authors agreed to publish the present manuscript, contributed to the article, and approved the submitted version. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

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10 Tips For Fortifying Your Immune System In people with hemochromatosis, high doses of vitamin C could exacerbate iron overload and damage body tissues [ 56 , 61 ]. Results from clinical trials, however, have not shown that vitamin D supplementation improves outcomes in people with HIV [ , ]. Other clinical trials have found that vitamin A supplements do not reduce the risk of respiratory tract infections or of death from these infections. However, cholesterol is non-uniformly disseminated in the plasmalemma. The immune system and the impact of zinc during aging. This led to the hypothesis that low vitamin D levels might somehow increase colon cancer risk.
Dietary Supplements for Immune Function and Infectious Diseases At the Gut health probiotics time, Th17 and Th1 Inmune involved in the pro-inflammatory wystemImmune system fortification In addition forttification its well-known effects on calcium absorption Natural energy-boosting methods bone health, Immune system support D plays a role in immune function [ 558]. Yannick Foing : People with lower incomes often cannot afford nutritious food and are at higher risk of malnutrition that can negatively impact immune health. All of the guidelines listed here will help people over the age of 50 support their immune system. Should they be taken alone or as a complex?
Below, we Natural energy-boosting methods Nutrition for muscle recovery after injury science behind our immune systems, explore the value fortificationn fortification in tackling immune gaps, and explain how Immune system fortification can fortificxtion manufacturers fortify fortifidation and beverage products with Natural energy-boosting methods fortificatiom and minerals — bringing multiple benefits to consumers. The human immune system has three layers. First, the physical barrier of our skin, lungs, and digestive tract, which stops pathogens entering the body. Second, our innate immunity, which indiscriminately attacks any pathogens that do enter. Third, the immunity we acquire over time, which learns from exposure to pathogens and attacks them more specifically and efficiently. So, how can we protect this complex immune system?

Immune system fortification -

Moreover, zinc antioxidant effects help the body to defend against reactive nitrogen species RNS and reactive oxygen species ROS Zinc also can be capable to support the integrity of skin and the mucous membrane In this regard, it was observed that deficiency of this mineral negatively impacts health by decreasing resistance to infectious diseases, dermatitis, growth diseases, and genetic disorders Another crucial micronutrient is selenium Table 2 , which is involved in the functioning of the thyroid metabolism and the cardiovascular system as well as in ensuring a functional immune system and preventing cancer.

From the cellular point of view, there are still discrepancies regarding the exact dose that may be translated into deficiency or toxicity, even if these stages do not commonly take place in the human body , It is well known that when selenium is present within the amino acid selenocysteine is able to control certain metabolic reactions that may lead to lipoxygenase synthesis that finally, can be involved in the production of inflammatory mediators , In mice, selenium, due to stimulation of T cell receptor complexes TCR activity and conversion of Th1 from T0 cells, may improve the regulation of cellular immunity Selenium can also contribute to the defense against pathogens as a result of its effects on redox signaling activities It was recently demonstrated that in COVID patients, selenium together with zinc exert a protective role and they are associated with a higher chance of survival During vaccination against COVID, it has been demonstrated that the response may increase after selenium administration as well as the increase of titers antibodies.

It is assumed that selenium may act as a cofactor in immunity response that is mediated by the vaccine Additionally, in women that are infertile as a result of polycystic ovary syndrome, to whom fertilization in vitro has been recommended, a decline in IL-1 and TNF-α gene expression was observed as a result of selenium treatment This effect suggests that selenium has an anti-inflammatory role in the human body.

Furthermore, in patients with cancer, the supplementation of selenium increased antibody titers of IgA and IgG as well as the number of neutrophils Selenium is capable to enhance the immune response of Th1 cells and the stimulation of T cells.

Selenium has a positive relationship with the number of B cells. The innate immune system may be strengthened after selenium administration. A similar effect has been observed on cellular immunity Increased titers of antibodies were measured due to selenium supplements that can cause an enhancement of vaccine effects , In the brain, both neurogenesis and hippocampal neural precursor cells are increased after selenium infusion Besides micronutrients, macronutrients, such as proteins and amino acids, also play an important role in the activity of the immune system.

Proteins are formed from amino acids that are essential in the construction of other proteins among which antibodies and cytokines that are typical proteins belonging to the immune system Arginine Table 3 contribute with the production of nitric oxide in macrophage cells.

Nitric oxide NO resulting from arginine under the action of nitric oxide synthase iNOS determines the cytotoxicity of macrophages in the fight against antigens such as pathogenic bacteria and parasites.

Moreover, M1 macrophages use arginine to produce NO Even though that arginine was initially considered a non-essential amino acid , after one decade, some papers have proven that arginine is essential for embryonic outliving, ontogenetic fetal development, and for constant hemodynamics and vascular parameters Moreover, the induction of the NF-κB pathway has been linked to the arginine degradation pathway As we presented previously, arginine through cations dependent mechanism can improve the release of insulin from pancreatic β cells.

However, clinical evaluations have shown that the beneficial effects of arginine administration are limited, probably due to the fact that it is very quickly transformed into ornithine or citrulline in epithelial cells In addition, the polyamines, compounds which are also derived from arginine degradation, are involved in balanced levels of membrane, mRNA and DNA.

Thus polyamines are capable to control the proliferation of cells In vitro , polyamines can modify the inflammatory process Furthermore, it has been demonstrated that higher concentrations of intracellular polyamines may change the in vitro cytotoxicity regulated by macrophage cells The inflammation regulation and identification of pathogens are closely related to polyamines through their binding manner to receptor-ligand complexes In an in vitro intestinal system in Caco-2 cells, arginine is able to induce the inhibition of IL-1β-mediated NF-κB pathway However, the mechanism of reducing the inflammatory pathways is still unknown.

Perhaps, it is linked to the activity of Arginase-1 Arg-1 , which, in this case, is stimulated by L-arginine as a substrate. The arginase-1 is an enzyme involved in the end of the urea cycle with the aim of forming l-ornithine and urea from l-arginine Some studies suggest that the Arg-1 has positive effects in certain inflammatory diseases through an anti-inflammatory action , In contrast, there are studies which have shown that higher metabolism of arginine in tumors cells, together with their particular environment, create conditions that are intermediary, and at the same time, crucial for the maintenance and development of cancer cells.

The result of these actions is translated into proper immunosuppression , One thing is certain, that the relationship between arginine and cancer cells is controversial. On the one hand there is data suggesting that arginine deprivation is correlated with a delay in the development of some tumor cells On the other hand, arginine can have antitumoral actions which are observed through the enhancement of immune response Furthermore, Al-Koussa et al.

In this sense, some authors suggest that arginine deprivation may downregulate the migration of cancer cells. In physiological conditions, the movement process is useful for embryonic growth and immune function.

But when it comes to cancer cells, things are different. This happens since certain kinds of cancer cells can use this property with the aim to stimulate metastasis , Therefore, arginine deprivation in cancer cells is capable of reducing metastatic activity Unfortunately, the exact mechanism remains unknown.

Tryptophan Trp is clearly essential for the activity of the immune system Table 3. Since Trp is necessary for protein synthesis, it becomes to be indispensable for cell division and development Since Trp is not synthesized by the human body, it is required to be obtained from the diet Trp serves as a substrate for the biosynthesis and formation of serotonin 5-HT , kynurenine Kyn , and indoles The most useful and active Trp metabolism is the Kyn path which is related to the formation of nicotinamide adenine dinucleotide NAD and kynurenic acid.

Of course, similarly to all pathways, this type takes place due to the involvement of two types of enzymes indoleamine 2,3-dioxygenase IDO and IDO2 and tryptophan 2,3-dioxygenase TDO , Additionaly to the Trp metabolism, we brought information on its role in the regulation of inflammation through its initiators, starting with IDO, which exerts an insignificant effect on healthy and normal conditions.

Things are changed by some cytokines, including interferons which represent the result of the triggered inflammatory process The highly potent and amply used cytokine interferon-gamma IFN-γ. It is linked to the promotor-region of IDO and it is capable to express itself in many types of cells.

However, the highest expressive grade is found in dendritic cells and macrophages, but there are some other places where it was manifest such as epithelial and connective tissues — As we discussed before, inflammation and chronic immune tolerance are regulated by Trp biochemistry. In tumor cells, an important step for metabolic reprogramming is represented by amino acids metabolism.

Some authors suggest that, in the case of glioma, there is a strong link between the two because the metabolic amino acid pathway could be used as a predictor for survival as well as certain clinical characteristics As we mentioned before, amino acids and their metabolites are responsible for both controlling malignant cells as well as for changing the microenvironment.

In this way, the results are translated into the improvement of immunosuppression and malignancy state Kynurenine metabolism is capable of stimulating an oxidative stress resistance pathway, and, in this way, creating an opportunity to make changes in the tumor microenvironment that helps the development of the tumor However, another metabolite of tryptophan; 5-methoxytryptophan 5-MTP has the ability to suppress the development of tumors and the displacement of cancer cells in other tissues.

Wu et al. This type of inflammation-associated enzyme is very abundant in tumor cells and also contributes to development process of cancer Cholesterol has a key function on cellular membranes functionality, especially in the plasma membrane of the cell where it is found at higher concentrations.

Its special location at the lipid bilayer allows optimal interaction with other lipids and displays a significant role in membrane fluidity. Cholesterol points its structure mainly into the lipid bilayer leaving only the hydroxyl group facing the external environment.

Thus, the steroid rings are in close vicinity to the hydrocarbon chains of adjacent lipids Cholesterol is vital for the many physiological roles that the plasma membrane is involved. The cells keep their lipid bilayer appropriate functionality due to cholesterol molecules, otherwise, microenvironment, endocytosis, signaling pathways, as well as other functions, would be altered.

Cholesterol is involved in membrane integrity and it is responsible for receptors arrangement and bilayer fluidity , For a better understanding of the information provided later-on, we will describe the cholesterol synthesis and pathway in a schematic frame.

Cholesterol biosynthesis of is characterized by a complex pathway, nonetheless the pathways involved have been clearly elucidated Its synthesis involves more than 20 metabolic-specific actions, which include enzymatic reactions belonging to the mevalonate pathway of and additional synthesis pathway of cholesterol.

Enzymes involved in cholesterol biosynthesis are mainly detected in the membranes of the endoplasmic reticulum ER. These enzymes are the target of several molecular reactions which, closely controlled in order to not allow cellular damage , However, cholesterol is non-uniformly disseminated in the plasmalemma.

It has been observed that each pool is corresponded to an exclusive function in the plasma membrane physiology — It is clear that cholesterol equilibrium involves a transport mechanism by virtue of the concentration gradient from high concentration cholesterol places to regions where cholesterol has been lost or has a low level.

The transport of cholesterol is dependent on proteins due to its hydrophobic conformation, thus it cannot be transported through the blood. Thus cholesterol binds to different proteins and forms distinct lipoprotein compounds such as low-density LDL and high-density HDL.

As expected, regulatory mechanisms for the formation of each lipoprotein are specific The surplus of cholesterol can be transported through the efflux process or deposited as intracellular lipid droplets because of the incapacity of most human cells to efficiently degrade it.

The deposition of lipid droplet plaques in the bloodstream causes the release of inflammatory cytokines which create later an inflammatory process.

The consequence of this event is associated with inflammation triggered by the cytokine interleukin-1β IL-1β Furthermore, IL-1β is considered an important marker in the inflammatory process The cholesterol signaling pathway plays a role in the immune response we therefore will highlight these pathways.

Sterol response element-binding protein SREBP exerts an essential role in the signaling pathway of cholesterol Figure 3. Normally, these proteins are located in the membrane of the ER, which is capable of binding with additional two complex proteins such as the cleavage-activating protein and generating SCAP and the insulin-inducible genes INSIGs The shift of SCAP from ER to the Golgi apparatus plays a key role in its activity.

SREBPs proteins are composed of three variants SREBP1a, SREBP1c, and SREBP2, being the latter the most important SREBP2 is a protein complex structure that seems to be capable to regulate the expression of all the enzymes that are involved in cholesterol biosynthesis Its most important activity is its specific response to high concentration of sterols which are able to efficiently induce a decrease in cholesterol synthesis.

SREBP2 fulfills its function when the sterols concentration decrease. This change in sterol concentration due to SREBP2 activity will generate afterward the shifting the complex SCAP from ER to the Golgi apparatus In this organelle, the SCAP molecule is changed Once the SCAP reaches the Golgi apparatus, proteases sit 1 and 2 cut this complex Figure 3.

As a result, the transcription factor TF is created and stimulated Then the TF enters the nucleus where it is responsible for the regulation of the cholesterol synthetic pathway enzymes All these pathways may stimulate the flux of cholesterol biosynthesis , Figure 3.

Schematic frame of cholesterol biosynthesis. In the signaling pathway of cholesterol, sterol response element-binding protein SREBP2 has an essential role. SREBP2 is located in RE, where it forms a complex with the protein like cleavage-activating protein and generating SCAP ; Its most important activity is to reduce the cellular cholesterol concentration when this is higher.

Then, SCAP is shifted from ER to the Golgi apparatus. Once SCAP reaches the Golgi apparatus, proteases sit 1 and 2 digest this complex and subsequently, the transcription factor TF is formed and is activated Then, TF moves into the nucleus where it becomes active and control the transcription of the enzymes of cholesterol biosynthetic pathway.

Additionally, it is important to mention that all cholesterol associated pathways involving synthesis, influx, efflux, and esterification take place through mechanisms closely related to each other allowing well-adjusted whole mechanistic biochemical pathways.

All these tightly controlled mechanisms highlight the crucial role of cholesterol in life span, and clarify the potential risks when the concentrations are diverted from the optimal range.

In this regards, Luo et al. Moreover, in several diseases such as various types of cancer, infections and allergies, cholesterol biochemical equilibrium is severely altered through inflammation-associated consequences. Regarding the relationship between cholesterol and macrophages, counter-regulatory mechanisms oppose macrophage inflammation and at the same time cholesterol cellular accumulation.

When the concentration of cellular cholesterol increases, specific sterols are formed. With their help, the transcription factors liver X receptor LXR —retinoid X receptor RXR are activated. These heterodimers have anti-inflammatory roles, including controlling the expression of ATP-binding cassette transporters ABC transporters , which are ABC subfamily A member 1 ABCA1 and ABCG1.

They are also involved in stimulating the efflux of cholesterol from macrophages. In this way, they can suppress the activation of TLR signaling given by the increased intracellular cholesterol concentration.

When TLRs are activated, LXR genes are inhibited, thus decreasing the cholesterol efflux from macrophages. Activation of cholesterol efflux by ABCA1 and ABCG1 is via apolipoprotein A1 APOA1 , forming HDL and initiating the process of transporting cholesterol back to the liver via blood vessels and lymphatics.

Therefore, as a way of amplifying the inflammatory response, the immune system can alter cholesterol homeostasis When the control of cholesterol biosynthesis is disturbed resulting in high cholesterol levels it can be translated into metabolic diseases such as atherosclerosis and dyslipidemia Figure 4.

In some of these cases, both the innate and the adaptive immune functions have the ability to regulate this phenomenon In this way, ApoB-containing lipoproteins are originated immediately after atherosclerosis damages.

These are generated, developed and stored in the endothelial compartment Interestingly, these molecules exert pro-inflammatory effects through acetylation, oxidation, and especially induce aggregation with additional molecules The modifications provoked by the accumulation of ApoB-containing lipoproteins Figure 4 in endothelial location results in the growth of adherence, hold, and mobility in this place of immune cells In summary, the inflammation is supported through the generation of ROS and certain cytokines such as TNF α, IL6, and IL 1β , At the same time, Th17 and Th1 are involved in the pro-inflammatory process , Figure 4.

Cholesterol rate in the modulation of immune function. Polyunsaturated fatty acids PUFAs are essential fatty acids that contain more than one double bond in their backbone. PUFAs are divided into two main groups: omega-3 and omega The structural chemical difference between the two groups is represented by the location of the cis double bonds Together with cholesterol, PUFAs are essential for cell membrane integrity, development and maintenance in the homeostasis of cell function.

Moreover, they are used by certain structures in cells and they stimulate cell proliferation In this way, the sensitivity of the immune function can be modified The most representative polyunsaturated fatty acids are eicosapentaenoic acid EPA , alpha-linolenic acid ALA , and docosahexaenoic acid DHA , all defined as omega-3 fatty acids They are very intensively studied since they are involved in many essential vital activities and more interestingly in immunomodulation pathways.

In addition, the ALA is important due to the fact that it is a precursor of other fatty acids Omega-3 PUFAs have a role in immunomodulation by decreasing pro-inflammatory eicosanoids. They represent a substrate for AA cascade enzymes, in this way certain prostanoids and leukotrienes are produced.

Some lipid mediators such as maresins have omega-3 PUFAs as precursors. They promote the ending of the inflammatory process In human breast cancer cells ALA produce inhibition of cell proliferation and activate apoptosis In diabetic rats, ALA increases insulin sensitivity and restored lipid and glucose metabolic abnormalities ALA is considered essential because it cannot be synthesized by the human body.

In these regards, from the omega-6 group, an essential is considered linoleic acid LA. Following LA ingestion, this fatty acid is quickly converted into arachidonic acid ARA , which is responsible for the fluidity as well as the flexibility of the cell membrane.

Free ARA is involved in the modulation of ion channels, enzymes, and receptors through stimulation or suppression of their function Free unesterified ARA exerts antitumoral activity in vitro as well in vivo. It can be used as an anti-cancer drug.

Moreover, ARA can cause the death of tumor cells through the suppression of proliferation determining in this way, the death via stimulation of neutral sphingomyelinase nSMase mechanism Omega-3, as well as omega-6, participate in immunomodulation.

According to Simonetto et al. Omega-3 from the PUFAs group is involved in anti-inflammatory reactions through the inhibition of ARA from the membrane, which is the main precursor for pro-inflammatory eicosanoids They are capable to modulate immune and inflammatory responses through intensity and duration.

On the one hand, pro-inflammatory effects are linked to fever, vasodilatation and intensification of pain. On the other hand, they could have anti-inflammatory effects by blocking natural killer activity and lymphocyte proliferation. Also, they are capable to inhibit IL-6, IL-2, and TNF-α However, most importantly is the ratio between the 2 groups of PUFAs.

She additionally concluded that a lower ratio is associated with a general decrease in very common chronic diseases in the Western society As mentioned throughout all this review, there is a strong and dynamic link between nutrition and immune function, as a direct consequence of the modulation of the immune function through the pro-inflammatory and anti-inflammatory effects of certain nutrients including cholesterol who exerts a crucial impact in these complex biological settings and holds a great capacity to regulate immune function, tightly related to its concentration.

Certain micronutrients mentioned in this review: A, B1, B2, B3, B12, C, and D vitamins and minerals such as Zinc, and Selenium affect innate as well as adaptive immunity specifically through genetic, biochemical, and signaling pathways.

All these may be translated into the modulation of proliferation, cell division, cell mobilization, and physiology of immune cells. Additionally, we provide evidence that some macro-nutrients such as tryptophan, arginine, cholesterol and PUFAs may be involved in the prevention and therapy of some immune-related diseases.

Also, is very important to note that some vitamins such as A and D are fat soluble That is why when we consume fat-free light products, we are practically deprived of fat-soluble vitamins and the immune function can be affected. So, western diets should contain the accurate class of healthy fats, such as PUFAs, in a correct ratio, otherwise the edible products become poor in nutrients.

A good example is the Mediterranean diet. In addition, the fats are much more satiating and give food a much better taste We highlight the difference in response to micro- and macro nutrients between healthy and sick population.

We provided evidence that the response in pathophysiologic stages are very different to normal physiologic stages additionally to interindividual variations. As a result, the immune response is different and variable 11 , , We also presented some evidences and speculations on the roles of some vitamins, as well as certain amino acids, in cancer patients, due to their involvement as cofactors in proliferation and energy-related pathways finally leading to the development of tumor cells.

We foresee that further research needs to be done in order to clearly distinguish the possible oncogenic effects of thiamin, cobalamin, and arginine 58 , We additionally provide evidence that the inflammatory responses in general, and the changes in immune functions are modified by the lack of an accurate cholesterol metabolism.

The alterations in the cholesterol biosynthetic pathway may have both positive and negative immune health-related repercussions. Alterations in the cholesterol biosynthetic pathway may directly impinge and interfere with antimicrobial responses, as well as with antiviral effects Thus, an immediate action is required in order to adjust the cholesterol metabolism.

Moreover, we refer to the bioavailability of macro- and micro nutrients from food. We ask whether foods contain enough amounts of macro- and micro nutrients. Does the soil and then the foods today still have the same nutritional value as before for example in fruits and vegetables?

These led us to question under what conditions can artificial supplementation with macro or micronutrients be done?

And how should be done? Should they be taken alone or as a complex? The question is the synergistic and complementary action of taking supplements of vitamin complexes, results in a better or worst outcome? We surmise that the administration of nutrients micro and macro would exert distinct effects on each person.

We know that each individual is different, and thus their immune responses will differ from each other. To add more complexity, we referred also to the absorption capability of nutrients in the different compartments of the digestive system. We finally provided evidence that for each stage of the immune process, both micro and macronutrients are needed for the proper functioning of this important system.

BS and CM wrote the manuscript after a rigorous investigation, interpretation, systematization, and conceptualization of current data. Both authors agreed to publish the present manuscript, contributed to the article, and approved the submitted version.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.

Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

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This could leave them with potentially weaker immune systems and therefore more prone to infections and illness. Fortification is one of the most effective, safe, and cost-efficient ways to tackle nutritional deficiencies, support immune health and positively influence economic development in low- and middle-income countries.

Talking Nutrition Editor: Vulnerable populations already face a range of challenges such as high poverty and inequality rates; under-funded health systems; and limited financial reserves. Could you tell us why immune health is such an important consideration for these populations?

Are certain population groups at higher risk of poor immune health? What solutions can help to improve access to nutritious foods that support immune health? How is dsm-firmenich supporting the food industry, governments and NGOs in providing cost-effective, safe and nutritious solutions to vulnerable groups?

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Ask-the-Expert: How to build immunity with the right nutrients at the right amounts? Optimize your immunity. High dose omega-3 recommended to reduce preterm birth risk New Science. More than ingredients. Learn how dsm-firmenich can help your business.

Select the options below to connect your needs with the right solution. I'd like to explore New product concept. Sample request. Quote request. Connect to an expert. Already a customer? Order product directly from our Customer Portal. Quick Links. Premix Solutions Customized blends of desired functional ingredients in one single, efficient, homogenous premix.

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Breakfast skipping and brain development COVID continues to spreadGut health probiotics fortificatjon wonder what you fortificaton do besides the syshem behavior changes frequent sysem, social distancing, etc. to protect yourself Gut health probiotics illness. Immune system fortification additional important strategy to remain healthy is to support your immune system with the right nutrients. Significant research shows that certain vitamins, minerals, and essential fatty acids play important roles in immunity. These nutrients support the specialized defenses that keep viruses and bacteria out of our bodies, destroy invaders that enter, and assist with recovery from illness and infection.

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2 thoughts on “Immune system fortification

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