Salt’s At Fault? Now What?

For years it was held that salt intake has a distinct influence on blood pressure and cardiovascular disease (CVD). In fact, in 2011 the American Heart Association issued a sweeping call for salt restriction (Appel, 2011), limiting intake of sodium to less than 1500 milligrams a day, which translates to approximately 3750 milligrams of sodium chloride. One teaspoon of salt, which is about 40% sodium and 60% chloride, has 2300 mg of sodium. Naturally found in most foods, sodium defies accurate measurement, but because men eat more food than women, they consume more. Nerve impulses depend on sodium for activation; otherwise you wouldn’t be able to open the link to this page. Overconsumption of sodium, however, can lead to calcium deficiency (Teucher, 2008). Once again, it’s a matter of balance…but not without at least a little controversy. Also in 2011, the Journal of the American Medical Association published a paper that discounts a relationship of salt intake to CVD. In a study that lasted for nearly eight years, researchers found the incidence of mortality and morbidity related to sodium intake to be minimal, with no translation to a greater risk of elevated blood pressure or CVD (Stolarz-Skrzypek, 2011). Contrary to conventional wisdom, low sodium was associated with elevated CVD risk. Now there, don’t jump for joy and a box of pretzels over one study. For every yin there’s a yang—potassium is the foil to sodium. Potassium is a mineral whose insufficiency is widespread. Most of us are fortunate if we get half the 4700 mg recommended every day. Maintaining the ratio, 2 to 1 in favor of potassium, offers considerable benefit to cardiovascular health (Yang, 2011). The bottom line in all this is that minerals need to be in, well, balance.

Still, excess salt intake is a way of life for some. In a fancy restaurant, you might be challenged to find salt and pepper shakers on a table, for fear of insulting the chef. At the corner diner, on the other hand... This temptation, or rather succumbing to the temptation, could be our downfall. Very recent papers published in the highly respected journal, Nature, deliver the news that salt intake may be associated with autoimmune diseases through a mechanism that turns certain of our immune cells into traitors. In autoimmune conditions, abnormal antibodies are produced and they attack the body’s own cells and tissues. Lupus, rheumatoid arthritis and type 1 diabetes are commonly known examples, but there are other disorders that have an autoimmune component. In each instance there will be a characteristic set of autoantibodies to attack normal cells. Sometimes the autoantibodies actually cause the tissue and organ damage; sometimes they’re only the markers of disease. Susceptibility to autoimmune disease could be blamed on environmental influences, genetic makeup, exposure to an infectious organism, or to a combination of these.

Newly identified in the study of autoimmune disease is a population of T cells called TH17, which produce an interleukin different from the run-of-the-mill T cells that assist other white cells in immunologic processes. Excessive numbers of TH17 cells are thought to play a vital role in autoimmune diseases (Harrington, 2005) (Stockinger, 2007), including multiple sclerosis, psoriasis, rheumatoid arthritis and Crohn’s disease. What these cells do is to fail to turn inflammation off. Inflammation is the body’s response to attack, whether from trauma, viral or bacterial infection, heat or whatever else might cause an insult. In this response a few things happen: blood vessels dilate, fluid may leak from the surrounding area and clot, cells swell, platelets get activated, macrophages show up to swallow damaged tissue, and the healing begins. We need inflammation to heal, but it has to stop before healing is complete. We take anti-inflammatory chemicals to stop the pain, but we also stop—or at least inhibit—the healing. TH17 cells are there to fight infections, normally targeting fungi and bacteria, but they need to control themselves. One of the factors found to instigate TH17 cells into aberrant activity is salt. In its presence, T helper cells are more likely to develop into TH17 cells that are pathogenic (Wu, 2013). Then they attack the body’s own cells.

Not surprising is that those who frequent fast-food joints were found to have elevated levels of TH17 cells. Why not, if this relationship is definitive?  Such establishments use salt to embellish flavor. Each of us has a gene that controls the physiological response to salt intake. In certain individuals, this gene is over-expressed by salt, leading to the pathogenicity of TH17 cells and subsequent inflammation (Wu, 2013). This effect is leading scientists to look more closely at low-salt diets in the treatment of autoimmune diseases. The good side of the original study is that several genes are implicated in the response, not just the one with the greatest impact. And it’s not likely that all are out of sync at the same time. Furthermore, the factors that initiate autoimmune disease need to be in concert. For most of us, they are not. For the rest, maybe hiding the salt shaker could make a difference. For those with type 2 diabetes, the difference would be substantial.

Appel LJ, Frohlich ED, Hall JE, Pearson TA, Sacco RL, Seals DR, Sacks FM, Smith SC Jr, Vafiadis DK, Van Horn LV. The importance of population-wide sodium reduction as a means to prevent cardiovascular disease and stroke: a call to action from the American Heart Association. Circulation. 2011 Mar 15;123(10):1138-43. doi: 10.1161/CIR.0b013e31820d0793. Epub 2011 Jan 13.

Charlton K, Yeatman H, Houweling F, Guenon S. Urinary sodium excretion, dietary sources of sodium intake and knowledge and practices around salt use in a group of healthy Australian women. Aust N Z J Public Health. 2010 Aug;34(4):356-63. doi: 10.1111/j.1753-6405.2010.00566.x.

Cook NR, Obarzanek E, Cutler JA, Buring JE, Rexrode KM, Kumanyika SK, Appel LJ, Whelton PK; Trials of Hypertension Prevention Collaborative Research Group. Joint effects of sodium and potassium intake on subsequent cardiovascular disease: the Trials of Hypertension Prevention follow-up study. Arch Intern Med. 2009 Jan 12;169(1):32-40. doi: 10.1001/archinternmed.2008.523.

Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, Weaver CT. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol. 2005 Nov;6(11):1123-32. Epub 2005 Oct 2.

Su M. Metcalfe Multiple sclerosis: One protein, two healing properties Nature. (15 September 2011); 477: 287–288 doi:10.1038/477287a

John J. O'Shea & Russell G. Jones Autoimmunity: Rubbing salt in the wound Nature. 06 March 2013 doi:10.1038/nature11959

Steinman L. A brief history of T(H)17, the first major revision in the T(H)1/T(H)2 hypothesis of T cell-mediated tissue damage. Nat Med. 2007 Feb;13(2):139-45.

Stockinger B, Veldhoen M. Differentiation and function of Th17 T cells. Curr Opin Immunol. 2007 Jun;19(3):281-6. Epub 2007 Apr 12.

Stolarz-Skrzypek K, Kuznetsova T, Thijs L, Tikhonoff V, Seidlerová J, Richart T, Jin Y et al Fatal and nonfatal outcomes, incidence of hypertension, and blood pressure changes in relation to urinary sodium excretion. JAMA. 2011 May 4;305(17):1777-85. doi: 10.1001/jama.2011.574.

Teucher B, Dainty JR, Spinks CA, Majsak-Newman G, Berry DJ, Hoogewerff JA, Foxall RJ, Jakobsen J, Cashman KD, Flynn A, Fairweather-Tait SJ. Sodium and bone health: impact of moderately high and low salt intakes on calcium metabolism in postmenopausal women. J Bone Miner Res. 2008 Sep;23(9):1477-85. doi: 10.1359/jbmr.080408.

Chuan Wu, Nir Yosef, Theresa Thalhamer, Chen Zhu, Sheng Xiao, Yasuhiro Kishi, Aviv Regev & Vijay K. Kuchroo Induction of pathogenic TH17 cells by inducible salt-sensing kinase SGK1 Nature. 06 March 2013 doi:10.1038/nature11984

Yang Q, Liu T, Kuklina EV, Flanders WD, Hong Y, Gillespie C, Chang MH, Gwinn M, Dowling N, Khoury MJ, Hu FB. Sodium and potassium intake and mortality among US adults: prospective data from the Third National Health and Nutrition Examination Survey. Arch Intern Med. 2011 Jul 11;171(13):1183-91. doi: 10.1001/archinternmed.2011.257.

Nir Yosef, Alex K. Shalek, Jellert T. Gaublomme, Hulin Jin, Youjin Lee, Amit Awasthi, et al Dynamic regulatory network controlling TH17 cell differentiation Nature. 06 March 2013 doi:10.1038/nature11981

*These statements have not been evaluated by the FDA. These products are not intended to treat, diagnose, cure, or prevent any disease.