Barriers to Entry – Salt; an Inflammatory Trigger

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Chronic consumption of a Western diet along with sedentary behaviour causes chronic metabolic inflammation (termed metaflammation) and is ‘memorised’ by innate immune cells through long-lasting metabolic and epigenetic cellular reprogramming. Suggesting that the innate immune system, thought to have no memory, can be programmed over time to adopt a fast memory induced response.

Thanks to modern medicine and public health measures, our population assessed life expectancy is much better today than it was 100 years ago. But an extended lifespan is accompanied by increases in a different set of diseases: the non-communicable and disabling diseases of old age such as cardiovascular disease, cancer and neurodegenerative diseases. Moreover, diseases linked to lifestyle changes, such as type 2 diabetes, obesity and chronic liver disease, are growing to epidemic proportions.

We recognise that a key risk factor for these diseases is a Western diet, typically described as high in calories and rich in sugars, trans and saturated fats, salt and food additives, but low in complex carbohydrates, fibre, vitamins and minerals.

Remarkably for the first time ever, life expectancy is projected to decline, and it is likely that this downward trend will accelerate as a result of the detrimental effects of the Western lifestyle on the health of the current generation of children. Hence, the extension of healthy life by the promotion of effective preventive measures as well as novel treatments for non-communicable diseases should be urgent goals of personal and public health efforts.

Salt (sodium chloride- Na+Cl) as part of the diet has enjoyed the role of being a condiment of great value. In some societies, salt was a symbol of purity, incorruptibility or even immortality. In Mahayana Buddhist tradition, salt is still believed to ward off evil spirits. In the UK a pinch of salt is thrown over the left shoulder to prevent evil spirits from entering the house when returning home from a funeral.

Salt is essential to health and without it, mammals will die. However, there remains an ongoing controversy about how much salt an individual should ingest to avoid adverse health consequences. The high levels of salt typically ingested in the Western diet have been implicated in numerous disorders, particularly cardiovascular disease.

Interconnected with this is the understanding that our health as with all organisms crucially depends on intact barriers against the external environment. When you consider how often the barriers are challenged in the mouth, stomach and gut as we eat, in the lung while we breathe or through the skin when we are exposed to exogenous factors, it is not surprising that multiple barrier mechanisms especially the mucosal immune system have evolved to work together to protect these important structures. It may surprise you to know that the essential electrolyte Na+ seems to be crucially involved in several of these processes.

Its already understood from animal and human studies that Western diet consumption disturbs the gut barrier integrity, which — together with dysbiosis — promotes the influx of harmful microbial products into the portal vein circulation and the induction of systemic inflammation.

In addition, this ‘leaky gut’ disturbs local immune cell signalling, causes an influx of inflammatory myeloid cells, promotes a switch of gut-resident macrophages from a tolerogenic to an inflammatory state and results in a loss of beneficial regulatory T cells.

In the gut, it appears that ingested salt alters the relative abundance of certain microorganisms, with direct consequences for your immunity. Furthermore, it seems that several types of immune cells are affected by increased sodium environments. Hyper salinity increases the phagocytic activity of M1 macrophages in response to different stimuli, leading to better clearance of bacteria and viruses, whereas it suppresses the functions of M2 macrophages. In the case of T cells, hypertonic Na+ concentrations markedly increase TH17 cell polarisation while suppressing Treg cell function, both of which may increase susceptibility to autoimmune disease. In effect it has positive and negative impacts on our immune responses – suggesting an adaptive capacity and flexibility when ingestion is modified.

It should be noted, however, that although the in vitro data on TH cells clearly implies Na+-specific effects, it is still a matter of debate whether salt-mediated effects on the sum of immune responses in vivo are due to Na+ only or are also due to chloride or increased osmolality and this will be determined in coming research papers. Studies addressing whether there is a causative relationship first showed that the consumption of a Western diet leads to both quantitative and qualitative changes in intestinal commensal bacteria communities (dysbiosis) and the metabolites they produce.

The re-shaping of the gut microbiome to reverse salt-induced dysbiosis through changes in lifestyle or the use of prebiotics (such as high fibre diets) or probiotics could be important to restore immune cell homeostasis and may therefore be a new approach for the treatment of chronic disorders such as cardiovascular or autoimmune diseases.

Recent data from the Prospective Urban Rural Epidemiology (PURE) study identified an optimal dietary salt intake, revealing a J-shaped association curve between Na+ intake and the risk of death. Whereas too much salt intake should be avoided to prevent cardiovascular events and autoimmune disease, too little salt might have an unappreciated influence on our health involving compromised immune defences.

As always, context and outcome are a variable translational curve and if people continue to seek simplistic valuations on what constitutes an optimal intake on a public health basis, many subtle variations will be missed. Sodium, it appears has a more interesting role in human health than perhaps we have been led to appreciate to date, and as in many cases it is the gut and the immune system that act as the sentinel tissues.

To date we can I think agree that un-modified Western diets contribute a negative impact on human health and one of their cheap and frequently over utilised ingredient – salt is a significant player, but that total exclusion is also a modifiable risk.

5 Comments. Leave new

  • Tracy Land
    3, May 2019 10:35

    This post doesnt make any distinction between the effects of commercially-produced table salt, of the type that is high in processed foods, and nutrient-dense natural (sea, rock/mountain) salt.

    • Michael Ash
      3, May 2019 10:53

      Hi Tracey, whilst there are accessory nutrients present in some of the rock salts, ultimately the sodium content is still released and must be metabolised, there may be some differentiators in terms of the minerals released, but there is no research that indicates this is a meaningful effect in relation to the immune system and related barriers. Once the minerals are released from the sodium, sodium will still impact bacteria, cell membranes and immune cells. The key point is that like all nutrients there is a differential curve of risk – which may be mitigated by complex sodium crystals but would not be eliminated.

  • Catherine Dignan
    3, May 2019 10:59

    The article raises more questions than it answers – take it with a grain of salt, perhaps? Presumably the reference here is to the refined sodium chloride used in the processed food industry as a cheap flavour enhancer, whereas natural unrefined sources of sea and rock salt come with trace amounts of electrolytes such as potassium, magnesium, etc. My understanding of the ill effects of excess refined and processed food in the standard Western diet are from not just an excess of sodium chloride but a deficiency of potassium, probably exacerbated by a lack of fruits rich in potassium and green vegetables in the diet as a whole. Other flavour enhancers such as monosodium glutamate, common in processed foods have been shown to contribute to metabolic syndrome and diabesity.

    “ ….. too much salt intake should be avoided to prevent cardiovascular disease ….. too little salt might have an unappreciated influence on our health involving compromised immune defences”. The article has already reminded us that salt with or without trace minerals is essential to life. Salt reduction per se in some studies has had no measurable effect on hypertension – probably because much bigger factors are at play: (processed) ‘ “foods” are generally engineered from dizzying arrays of highly refined carbohydrates; the consumption of which is associated with obesity, unhealthy lipids, high blood pressure, and insulin resistance, all as part of a broader metabolic syndrome’. Intimate links between cardiovascular, metabolic and cognitive function are already well established. The solution seems simple: “Eat real food, mostly plants, not too much”, as Michael Pollan (should have) said.

    • Michael Ash
      3, May 2019 16:33

      Hi Catherine – the key message is as always, that personal variation in response to sodium and its accessory element chloride includes changes in immune responses. Rock salt may have 2% or so of potassium and magnesium but are still approximately 98% sodium chloride. You are correct in that refined foods utilise large quantities refined salt and that western diets are low in potassium generally. More importantly whilst general agreement exists that salt of all sorts in high levels compromises health, this piece was to highlight the more recent understanding of its impact on the immune system in the gut, via a combination of cell changes, eubiotic deviation and increased barrier permeability.

  • Asfia Aftab
    3, May 2019 16:58

    Thank you Michael, this is fascinating and a much overlooked area as we all obsess over carbs and fats. The link with the gut microbiome is also very interesting and I will be using this information to inform my lifestyle management plans. This may also help to understand the problem of patients who make great changes to a more anti inflammatory lifestyle, yet still seem to be suffering. I think there is still so much to learn about the immune system and metaflammation. But thank you for raising the issue of salt in a different light.


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