According to a new study, having too much sodium in the blood can cause the immune cells in the body to produce less energy. The effect may cause the immune cells to not work as well as they should, which is a major concern in the midst of a pandemic.

While having some salt in your diet helps balance fluids in the body and helps keep your heart and nerves functioning, consuming too much sodium has been linked to high blood pressure and may even raise your risk of premature death. Research has shown that consuming excess salt can cause blood serum sodium levels to get too high.

As a result, sodium can accumulate in places it shouldn't—like sites of inflammation in the body. Because immune cells play a role in the body's inflammatory response, this can ultimately can affect how well those immune cells function.

Along with the tried-and-true strategies to support the immune system—like including enough vitamin C in your diets, getting adequate rest, and staying hydrated—making sure that you are not consuming too much salt can help keep your body in fighting shape.

The authors of the new study, which was published in the journal Circulation, highlight that past data has shown higher sodium concentrations in the blood affect both the activation and the function of cells that play a role in immune system function. The researchers were able to show that immune cells are negatively affected by too much sodium, specifically by experiencing challenges with the way they produce energy.

The study found that salt can inhibit an enzyme that plays an important role in the respiratory chain, causing the cells to utilize less oxygen.

It's important to note that the researchers only evaluated cells that play a role in immune health for their research, and didn't test actual humans. The researchers also analyzed the results of two clinical trials. The first study evaluated the effects of eating pizza a high sodium food on certain cells found in the blood that play a role in immune health.

The second evaluated the effects of taking a salt tablet in conjunction with eating a typical diet. The results of the analysis indicated that the negative effects of salt intake can occur after a single high-salt meal, but that the effects were not long-lasting.

The Dietary Guidelines for Americans recommends that most people consume a maximum of 2, milligrams of sodium a day—about 1 teaspoon of salt. Some people need to limit their sodium intake even more, depending on their health.

The biggest contributor to excess sodium in the American diet isn't the salt shaker at the dinner table—it's restaurant foods and processed foods. Most people far exceed the recommended limits on salt intake by consuming processed, prepackaged foods, fast foods, and preserved foods.

Salt is a popular flavoring that many people enjoy, but there are other ways to achieve a satisfying taste without the detrimental health effects of excess sodium. To combat the extra dietary salt, Anzlovar says people should "focus on eating mostly whole foods, including lots of fruits and vegetables, which contain potassium and can help balance out sodium intake, and limit packaged and processed foods when managing sodium levels in the diet.

While it's gotten a bad rap in the past, monosodium glutamate MSG is a safe seasoning option that offers a similar flavor if you're trying to reduce your sodium intake. Here are some other tips for lowering your salt intake :. The results of this study were published in the journal Science Translational Medicine.

Eating a high-sodium diet on the regular is likely to increase your susceptibility to a myriad of opportunistic infections. That extra burger or pack of French fries could be the reason for your failing health. This translates to a level teaspoon of salt each day.

Most adults consume 7 to 9 grams of sodium per day, which means a majority of adults in the U. have an increased risk of developing hypertension and as well as immune-related conditions.

Was this finding unexpected? The researchers admitted that it was since a number of studies have indicated the contrary.

Lab studies have shown that a high-sodium diet helps to treat certain skin parasites, leading researchers to conclude that salt has an immune-enhancing effect. The research by Bonn University shows that the generalization that salt is good for your immune system is inaccurate.

The lead researcher, Katarzyna Jobin, observed that higher sodium concentrations are stored in the skin while the concentration in the blood and cells is maintained at a constant level. Biological processes would otherwise be impaired if sodium levels keep fluctuating after every meal.

The excess sodium consumed is usually filtered out of the body through the kidneys. A sodium chloride sensor is triggered during this process and causes the accumulation of glucocorticoids in the body. It is this accumulation of glucocorticoids that inhibits the action of important immune cells known as granulocytes.

Cortisone is a type of glucocorticoid that is often used to treat autoimmune diseases because of its immune-suppressing properties. High sodium intake is not only bad for your immune system but also a risk factor for obesity and insulin resistance.

While salt does not have any calories of its own, it increases appetite and makes you consume more food. The downstream target for the P38 gene, the nuclear factor of activated T cells 5 NFAT5 , induces the production of IL [ 32 ], which up-regulates the production of pro-inflammatory mediators [ 33 ].

All these findings suggest that a high salt diet might be the plausible environmental trigger for immune-mediated inflammatory diseases [ 20 ] Figure 1. Role of high sodium chloride concentration in mediating autoimmune diseases. It is known that the lamina propria of the small intestine serves as the main residing place for immune cells [ 35 ].

The immune function of the intestine is also modified by intestinal bacteria, which was demonstrated where gut microbiome free mice showed an increased Th17 response and developed various immune-related diseases compared to normal mice [ 36 ]. Li et al. showed that the reconstitution of gut microbiome free mice with intestinal bacteria leads to suppression of the Th17 response and enhancement of T regulatory Treg cell function [ 37 ].

High salt consumption has a direct effect on gut microbiota and immune cells of the intestine, producing variable effects. A high concentration of salt in diet was found to have a direct toxic effect on gut microbiota, especially on Lactobacillus murinus.

Lactobacillus murinus depleted mice were found to have an exaggerated Th17 response compared to normal mice. Oral gavage of L. murinus to these mice diminished the Th17 response, which confirmed that a high salt diet increases the Th17 response [ 37 ].

Recently, Maeda et al. found that intestinal Th17 cells can migrate to distant sites. For example, intestinal Th17 cells were identified in the spleen of RA patients. This confirms the role of intestinal cells in systemic immune inflammation [ 38 ].

Animal studies have shown the effect of a high salt diet on immune cells of the intestine. Mice receiving high salt tend to have exacerbated colitis and inflammatory diseases of the bowel.

This was associated with an enhanced pathogenic T cell response, autoantibodies, inflammatory immune mediators and a decrease in the protective immune response [ 39 ]. It has also been reported that an increase in inflammatory monocyte count and pro-inflammatory cytokines such as IL-6, IL, and IL was seen in healthy volunteers receiving a controlled high salt diet.

To reveal the molecular mechanism behind the enhancement of the inflammatory immune response by increased salt intake, lamina propria mononuclear cells LPMC were grown in medium with higher salt concentration and they were found to express higher levels of pathogenic inflammatory mediators such as IL and TNF-α along with an increase in the percentage of LPMC [ 41 , 42 ].

High salt concentration also induces ILR expression, whose main function is to stabilize and increase Th17 expression [ 43 ]. All these effects lead to inflammatory disease of the bowel Figure 2.

Role of high sodium chloride concentration in mediating inflammatory diseases of the bowel. These results show that gut immune cells and intestinal bacteria regulate the systemic immune response.

Hence it is important to note that dietary habits such as a high salt intake may be harmful and may have deleterious effects on health. Worldwide, increased blood pressure is one of the leading causes of mortality [ 44 ].

Hypertension leads to several life-threatening complications and has to be treated vigorously [ 45 — 47 ]. It has been established that salt intake is associated with hypertension, and recently it was found that immune cells grown in a high salt medium differentiate into highly pathogenic Th17 cells [ 48 ].

Interleukin 17 is the inflammatory marker produced by Th17 cells and is associated with hypertension. All the above effects ultimately increase the systemic vascular resistance, resulting in hypertension Figure 3. Various studies have shown the role of IL in the pathogenesis of hypertension [ 50 ].

Recently, Kamat et al. demonstrated that mice lacking ILA have increased potency to excrete sodium and hence reduction in blood pressure [ 51 ]. Hence blocking the activated immune cells and inflammatory mediators produced by it can prevent hypertension.

This was elucidated in an animal study where mycophenolate mofetil, a drug that is known to inhibit activation and proliferation of immune cells, prevented the development of salt-induced hypertension in rats [ 52 ]. Machnik et al. observed that high salt-treated rats acquired a pro-inflammatory M1 macrophage response and also exhibited water retention, leading to high blood pressure [ 53 ].

In addition to the immune-mediated mechanisms, a high salt diet was also found to modulate the renin-angiotensin-aldosterone system [ 54 , 55 ] and increases sympathetic tone, thereby elevating the blood pressure [ 56 ]. Reducing salt intake in the diet could be the simplest, most cost-effective, sustainable and easiest way to prevent the development and progression of hypertension.

The effect of salt concentration on cancer development was first proposed in the s, when Spars et al. initially showed that there was a high concentration of salt in human breast cancer tissue when compared to normal breast tissue [ 57 ].

Later, several studies showed a positive correlation between up-regulation of the sodium channel and tumor progression [ 58 — 60 ]. As discussed earlier, a high dietary salt intake causes stable induction of Th17 cells and induces inflammatory cytokines IL-1, IL-6, IL, TN [ 61 , 62 ] and inflammatory mediators such as prostaglandins, leukotrienes, transforming growth factor TGF , and inducible nitric oxide synthase iNOS [ 63 , 64 ].

Chronic induction of Th17 cells by high salt intake results in chronic inflammation [ 65 ]. Chronic inflammation exerts pleiotropic effects and is one of the important hallmark features in cancer development and progression [ 66 ].

Cells under normal environmental conditions utilize glucose in the aerobic glycolytic pathway but cells grown under a high salt environment tend to produce lactic acid, which provides a favorable environment for the cells to proliferate uncontrollably and to evade host immune defense [ 67 ].

This was confirmed by Amara et al. in a breast cancer cell line study, where the cells shifted to anaerobic metabolism under osmotic stress; this demonstrated the direct effect of high salt concentration on cancer cells [ 68 ].

Angiogenesis is one of the vital factors for the tumor to expand and survive [ 69 ]. Vascular endothelial growth factor VEGF is a well-recognized factor known to induce angiogenesis [ 70 ].

Recently it was demonstrated that a high salt environment induces the nuclear transcription factor NFAT5, which favors the production and expression of VEGF needed for the tumor microenvironment [ 71 ]. Apart from NFAT5, VEGF is also induced by IL, a hallmark proinflammatory cytokine produced by Th17 cells [ 72 ].

The immunological balance between Th17 cells and regulatory T cells Treg cells was disturbed in the high salt environment. A high salt environment triggers an increase in the number of pathogenic Th17 cells that disturbs the immunological milieu, causing chronic inflammation.

Chronic inflammation is one of the well-known predisposing factors for the development of cancer [ 73 ]. The available systemic reviews [ 67 ] and prospective studies [ 74 ] indicate that there is a strong association between high salt diet and cancer risk.

Hence reducing the salt content in the diet as recommended by the WHO [ 75 ] will reduce the disease burden in the population, and it will be a cost-effective way for disease prevention.

A high salt NaCl diet has various effects on the complex immune system leading to the activation of diverse inflammatory mediators which share the common inflammatory pathway. In autoimmune disorders, osmotic stress induces the activation of the stress kinase gene p38, which in turn activates several downstream mediators, notably NFAT5 and SGK1, leading to stable induction of proinflammatory Th17 cells.

In inflammatory bowel diseases, a high salt diet was found to affect the gut immune system as well as the microbiota. By disrupting the homeostasis in the gut, a high salt diet leads to activation of inflammatory mediators which are involved in activation and recruitment of Th17 cells.

A high salt diet affects the endothelium of blood vessels by reducing the availability of nitric oxide, mediated by IL, leading to the stiffening of the blood vessels.

Additionally, IL was found to reduce the excretion of sodium via the kidneys, resulting in its accumulation in serum. By these mechanisms, a high salt diet increases systemic vascular resistance, leading to hypertension. A high salt diet provides a favorable environment for the tumor cells to survive and proliferate.

High salt concentration in the tumor tissue favors the production of lactic acid, which protects the tumor cells from immune attack. In addition, high salt also favors angiogenesis by increasing VEGF, thereby providing nutrition to tumor cells and promoting tumor cell growth and proliferation.

Though high salt consumption has several deleterious effects on human health, lack of awareness among the public results in continued high salt usage and hence an increase in the incidence of IMIDs. Studies to explore the association between high salt usage and immune-mediated inflammatory diseases are in the initial phase or limited.

By extensively studying these molecular pathways, various pharmacological drugs targeting the IMIDs can be explored. By creating awareness among the general public, the disease burden caused by excessive salt intake can be minimized.

Available evidence suggests that there is a high likelihood of a high salt diet being implicated as a risk factor for several diseases including cancer, hypertension, and cardiovascular diseases.

This article is an attempt to highlight the harmful effects of these dietary habits and would like to emphasize the importance of reducing salt content for health and disease.

There is a lacuna in the literature regarding the possible mechanisms through which a high salt diet can act as a risk factor for several diseases mentioned in this article, which need further probing.

Current issue Archive Manuscripts accepted About the Journal Editorial office Editorial board Abstracting and indexing Subscription Contact Ethical standards and procedures Most read articles Instructions for authors Article Processing Charge APC Regulations of paying article processing charge APC.

Manuscripts accepted. About the Journal Editorial office Editorial board Abstracting and indexing Subscription Contact Ethical standards and procedures Most read articles. Instructions for authors Article Processing Charge APC Regulations of paying article processing charge APC.

Current issue. High dietary salt intake activates inflammatory cascades via Th17 immune cells: impact on health and diseases.

Yuvaraj Balan 1. Rajaa Muthu Packirisamy 2. Mohanraj P S 3. Pondicherry Institute of Medical Sciences, Kalapet, Puducherry, India. Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India. The incidence of immune-mediated inflammatory diseases IMIDs is on the rise.

A high salt content in the diet was found to play a crucial role in mediating IMIDs. In auto-immune diseases increased salt concentration causes stable induction of Th17 cells. In cancer, increased salt concentration triggers chronic inflammation and increases vascular endothelial growth factor levels.

Salt-mediated proliferation of Th17 cells has been found to reduce nitric oxide production in the endothelial cells, leading to hypertension. Increased salt concentration was found to alter the intestinal flora, which favors local inflammation. This review attempts to explain the role of high salt concentration and its molecular pathways in causing IMIDs.

Introduction Table salt NaCl is an essential component and an important ingredient in food. High salt in the diet in auto-immune diseases Autoimmune diseases comprise various inflammatory diseases, such as rheumatoid arthritis RA and psoriasis [ 21 ].

Figure 1 Role of high sodium chloride concentration in mediating autoimmune diseases. Effect of high salt diet on gut microbiota A high concentration of salt in diet was found to have a direct toxic effect on gut microbiota, especially on Lactobacillus murinus.

Effect of high salt diet on immune cells of the intestine Animal studies have shown the effect of a high salt diet on immune cells of the intestine. Figure 2 Role of high sodium chloride concentration in mediating inflammatory diseases of the bowel. High salt in the diet and hypertension Worldwide, increased blood pressure is one of the leading causes of mortality [ 44 ].