The Entropy is our fiercest enemy, and the salt is his perfect food.
Ignored (non-communicable) knowledges and bad education overall, and in the health science too. The law of entropy is the fiercest enemy of life and is our fiercest enemy too. The sodium-chloride isn't food for humans, but is the perfect food of entropy. The spontaneous diffusion of sodium ions into the cells and the diffusion of potassium ions out of the cells, enhances the entropy (the mesure of disorder). And every mmol excess sodium and the wrong sodium/potassium ratio (and other wrong ratios) increases more the entropy in our body, in every cells. The task of the continuously working sodium-potassium pump to keep constant the intracellular concentration of Na and K ions. These cellular pumps continuously use energy of ATP molecules. "The activity of Na-K pump has been estimated to account for 20-40 % of the resting energy expenditure in a typical adult." (1) Some consequences of high sodium intake; the specialists talk about these rarely or never: Higher energy requirements (energy expenditure) for Na-K pump and kidney. All the rest of our vital processes (functional processes of the cells) receive less energy - because the metabolic rate (speed and capacity of enzyme reactions, oxygen supply, etc.) is limited. And the excess sodium intake do not increase the oxidative pathway. But, a critical surplus switches the anaerobic glycolysis on, in our every cells. This can be named: Sodium-Induced Cellular Anaerobic Glycolysis (SICAG). I think (it is logical) this is a very old anaerobic cellular mechanism, before free oxygen on Earth. We produce lactic acid in our every cells. Consequently, all of our vital processes and organs work worse (our heart, brain, regulating systems, immune system, etc.), and our cells are dying. Remains less energy for the regeneration. We burn the candle on both of his ends (aerobic and anaerobic). The average lifetime of our cells shortens. Soon (faster) the telomeres run out. Our aging accelerates. We get sick often and we will die soon. Logical consequence; the unnecessary sodium increases the incidence of all illnesses. Searching in 12 book set of Dietary Reference Intakes (more than 5000 pages, and about 600 references in the chapter; Sodium and Chloride) no hits for entropy, and the sodium-potassium pump is only some empty phrases. (2) The blind watchmaker learned well the physics first, then the chemistry, and dealt with biochemistry then only. But he never forgot what he learned already once. The optimal Na/K ratio and the ratio between sum of alkaline metals and sum of polyvalent metals, and the ratio between alkaline metals and energy content, etc. is in the human milk. From every viewpoint, the human milk is an evolutionary perfect food, including the minimal energy expenditure of the Na-K pump and kidney of the babies (= possible minimum entropy-transfer into the babies = the baby is growing healthily and with maximal economicalness). Thus, the human milk is the perfect guide to calculate the optimal adult intakes. Unfortunate, that these exist only in traces, in the scientific literature. And in some articles, even the traces are concealed. This is the real wicked problem of health sciences, and this is wronger than malignant neglect. I collected the most important evidences (the traces, and lack of the traces) of the above ones. Let us see it in a logical and nearly chronological order.

 1965. Klahr&Bricker: Energetics of Anaerobic Sodium Transport by the Fresh Water Turtle Bladder. (3)
I quote from this: "The rate of anaerobic glycolysis, as determined by lactate formation, correlates well with the rate as determined by glycogen utilization. Using lactate formation as the index of anaerobic glycolysis, a linear relationship was observed between glycolysis and net anaerobic sodium transport."
Oops, sodium transport, anaerobic glycolysis and lactic acid, in 1965!

And 35 years later, 2000. Therien and Blostein: INVITED REVIEW - Mechanisms of sodium pump regulation. (4)
I don't quote from this, because are 362 references in the article, but nothing about the anaerobic glycolysis and lactic acid. Why?

And 40 years later, 2005. Christopher B Scott: Review, Contribution of anaerobic energy expenditure to whole body thermogenesis. (5)
Some quotations from this: "Entropy represents energy that is not available to perform work so that simply put, energy transfer is inefficient. ... Brisk activity of the sodium pump necessitates a rapid rate of ATP re-synthesis. If this is true then it is important to recognize that in some cells lactate with presumed heat production is better correlated with sodium and potassium pumping than is oxygen uptake. ... It seems logical to conclude that most mammalian energy expenditure does come from aerobic metabolism but the evolution of a metabolic acceleration with concomitant heat production comes from both anaerobic and aerobic pathways. The relative contributions of each pathway to whole-body thermogenesis are not known."
This already something (entropy, sodium-potassium pump, anaerobic glycolysis and lactic acid, in one article) but not too much. The explanation of the correlations and the consequences are missing. Would this be the "progress" of the health science over 40 years? Why "in some cells" only? I think so, in every cells (generated by high sodium intakes) and this is the cruel reality!

And 43 years later, 2008. Morrison et al.: Central control of thermogenesis in mammals. (6)
Again, I don't quote from this, because ~ 180 references are in the article, but nothing about the entropy, (floor gas) Na-K pump, anaerobic glycolysis and lactic acid. How can the knowledge (which was found already once or more) disappear?

1985. Henningsen: The sodium pump and energy regulation: some new aspects for essential hypertension, diabetes II and severe overweight. (7)
Again I quote (the abstract): "There is a growing evidence for that in modern societies the function of the cellular sodium-potassium pump (membrane-bound Na+ K+ ATPase) in several tissues in man cannot respond adequately to demands. This is not seen in any other free-living vertebrates on this earth. The clearly unphysiological very high intake of sodium-chloride (salt) and also alcohol is definitely playing an important role in the development of the common degenerating metabolic aberrations, e.g. essential hypertension, diabetes II and severe overweight, in man. The special and overall important role of the sodium-potassium pump for optimal cellular function and regeneration with special reference to the vascular tissues is presented and discussed."
Oops, the floor gas sodium-potassium pump (anaerobic turbo pump) is not enough, our cells are dying. And this was clear in 1985!

1991. Nedergaard et al.: Acid-induced death in neurons and glia. (8)
From the article: "Cerebral hypoxia-ischemia induces lactic acid formation trough the accentuation of anaerobic glycolysis. The magnitude of this lactic acid accumulation depends largely upon the preischemic glucose and glycogen concentrations of the affected tissue (Smith et al., 1986). Local accumulation of lactic acid to cytotoxic levels may play a causal role in the genesis of brain infarction following cerebral ischemia (Meyerand Yamaguchi, 1977; Siemkowitz and Hansen, 1978; Pulsinelli et al., 1982; Nedergaard, 1987). Several authors have addressed directly the issue of acid-induced cell death."
And the excess sodium intake (floor gas Na-K pump) also induces lactic acid formation by switching the anaerobic glycolysis (SICAG) on. And our cells are dying, even in our brain. The salted humanity degenerates and will be idiotic.

2001. Osaka et al.: Thermogenesis induced by osmotic stimulation of the intestines in the rat. (9)
 Some details from the article (here are some concealed traces): "The energy expenditure induced by 20 % glucose was 2.79 +/- 0.45 kJ kg-0.75 for 3 h (Fig. 4). The RER (respiratory exchange ratio) increased from 0.82 +/- 0.01 to 0.92 +/- 0.01 at 115 min (Fig. 1B), suggesting the oxidation of carbohydrate ... The metabolic rate rose during the 10 min infusion period of 3.6 % NaCl, stayed at a plateau level of ~ 205 J kg-0.75 min-1 between 35 and 120 min and then slowly declined but was still significantly higher than the baseline level at 3 h. The energy expenditure induced by 3.6 % NaCl was 3.49 +/- 0.33 kJ kg-0.75, ... The RER did not change after infusion of any of the NaCl solutions (Fig. 2B)." 
These results proves clearly, the excess salt intake (the higher energy expenditure of the Na-K pump and kidney, against entropy) do not increase the oxidative pathway, in rats. (I notice it: the decrease would be logical? Yes, it is logical consequence of the sodium-induced disorder. And I think, the decrease is fact!) But a critical surplus switches the anaerobic glycolysis on, and produces lactic acid in every cells. We can calculate that this anaerobic energy (ATP) production consumed more glucose (from the glycogen reserve) than the total resting metabolism of the rats, on the oxidative pathway. Despite, that this anaerobic excess isn't more than (about) 10-15 % of the total resting metabolism of the rats. And after the infusion of the highest dose of salt, 3 hours was not enough to return to the baseline level (to the level of resting metabolism). This is a real Sodium-Induced Cellular Anaerobic Thermogenesis (SICAT) or SICAG. From the effects of 0,9 % and 1,8 % NaCl infusion, I can suppose, anaerobic glycolysis begin in an average 70 kg adult from ~ 6-7 g dose of salt. I would dare to bet, that this was examined in similar (but oral) human experiments already, but where are the results? Furthermore, from the above results roughly calculable: the salted humanity squanders the energy of at least 100 million tons of food annually, to get rid of the sodium swallowed unnecessarily. We overeat (devour), we get fat, we get sick, and we die, while millions are starving on Earth.

And 9 years later: 2010. Ram K. Mathur: Role of diabetes, hypertension, and cigarette smoking on atherosclerosis. (10)
 From the article: "To determine the mechanism of thermogenesis, Osaka et al.[7-9] infused hypertonic solution of glucose, NaCl, ... The mechanism of thermogenesis is not clear. However, it may involve intestinal osmoreceptors. ... It is this thermogenesis that is responsible for the generation of atherosclerotic plaque."
From the end of the article: "Patients are advised to stay away from fatty foods, which obviously does not help because fatty meal is not the cause for atherosclerosis. Therefore, the researchers should first examine the cause of the disease before trying to cure it; otherwise, we will be treating symptoms rather than curing the disease itself. ... Finally, this field requires some broad theories and hypotheses explaining the involvement of foods, diabetes, hypertension, cigarette smoking, and others in the formation of atherosclerotic plaque. We have a mission but are lacking the vision. That is why we have not made any progress even though we have worked on it for more than 50 years."
In these two articles (Osaka et al. and Mathur) absolutely nothing about entropy, Na-K pump, anaerobic glycolysis and lactic acid. Bad education, oblivion or something else? 9 years and 45 years after Klahr&Bricker, and the mechanism of thermogenesis was not clear really, for the authors and editors? Or ...? The floor gas (anaerobic) sodium-potassium pump devours the energy (and we produce lactic acid), but it's not enough, and our cells are dying. We haven't enough energy, and we haven't enough time for the regeneration, because we enhances the entropy (by high salt intakes) in our every cells, day by day, again and again, the entropy devours our energy. All the rest of our vital processes (functional processes of the cells) receive less energy, and all of our organs and vital processes work worse (including our heart, brain, regulating systems, immune system, etc). This is responsible for the generation of atherosclerotic plaque. And this is responsible for the low physical activity. And this generates strong hunger (and thirst). We overeat and get fat. And indisputable consequence, that the unnecessarily swallowed excess sodium increases the incidence of all illnesses, without any exception, including even the genetic disorders, cancer, NCD's and infectious diseases. Some people will be obese others not, some become diabetes others not, some have high BP others not (or later), etc. We are not totally alike, but the entropy law finds our weak point, and ravages mainly there, but increases the disorder in every cells in our body (and other risk factors affect the individual consequences).

2005. Meneton et al.: Links between dietary salt intake, renal salt handling, blood pressure, and cardiovascular diseases. (11)
From the abstract: "The mechanisms by which dietary salt increases arterial pressure are not fully understood, but they seem related to the inability of the kidneys to excrete large amounts of salt. From an evolutionary viewpoint, the human species is adapted to ingest and excrete < 1 g of salt per day, at least 10 times less than the average values currently observed in industrialized and urbanized countries."
Is valuable the evolutionary viewpoint in the article, but 40 years after Klahr&Bricker and 20 years after Henningsen, why "not fully understood"?

2011. Dickinson et al.: Endothelial function is impaired after a high-salt meal in healthy subjects. (12)
From the article: “However, the mechanisms relating salt and endothelial dysfunction are still not clear.”
26 years after Henningsen, why "still not clear"? The progress of the science has been stopped!

1998. Sandor Z.: Equivalency law in the metal requirement of the living organisms. (13)
This equivalency law is a simple chemical rule: The alkaline metal requirement (sodium + potassium) is chemically equivalent with that of polyvalent metals (calcium + magnesium + zinc + iron etc.). Because, is a strict chemical stoichiometrical rule of the cation exchange processes is that they proceed with the exchange of an equivalent amount of positively charged counter-ions. The counter-ions of the polyvalent metals in our body = Na + K. Less counter-ion = trouble, much counter-ion = trouble, very much counter-ion = catastrophe, especially together with lactic acid formation! The average metal content of the breast milk proves this law, surprisingly well. But the scientists do not deal with this fact.

2005. Yamawaki et al.: Macronutrient, mineral and trace element composition of breast milk from Japanese women. (14)
From the results of this article we can calculate our own optimal intakes, and main optimal ratios. (Although this is only one article, and there is not much one like this in the literature.) For example, the optimum of sodium for an adult is not more than 400-500 mg/day. And the optimal sodium:potassium (mass) ratio is approximately 1:4. The mammalian milks and the human milk are evolutionary perfect foods, we must use this knowledge!

2013. WHO Guideline: Sodium intake for adults and children. Geneva, World Health Organization (15)
Sodium intake printversion; on page 2 (10 of 56):"WHO recommends a reduction in sodium intake to control blood pressure in children (strong recommendation). The recommended maximum level of intake of 2 g/day sodium in adults should be adjusted downward based on the energy requirements of children relative to those of adults."
Why downward? Why not from mature human milk?
On page 3 (11 of 56): "Addressing the optimal ratio of sodium to potassium was outside the scope of this guideline; however, if an individual consumes the amount of sodium recommended in this guideline and the amount of potassium recommended in the WHO guideline on potassium intake, the ratio of sodium to potassium would be approximately one to one, which is considered beneficial for health [12]."
and on page 19 (27 of 56): "These recommendations do not address the optimal sodium to potassium ratio; however, if this guideline and the WHO guideline on potassium intake are achieved, the molar ratio of sodium to potassium would be approximately one to one."
  Potassium intake printversion; on page 3 (11 of 52): "... however, if an individual consumes sodium at the levels recommended in the WHO guideline on sodium intake, and potassium as recommended in the current guideline, the ratio of sodium to potassium would be approximately one to one, which is considered beneficial for health [8]."
and on page 16 (24 of 52):"These recommendations do not address the optimal ratio of sodium to potassium; however, if this guideline and the WHO guideline on sodium consumption are achieved, the molar ratio of sodium to potassium would be approximately one to one."

[12] = [8] (this is a self-reference) = WHO Diet, nutrition and the prevention of chronic disease. Report of a Joint WHO/FAO Expert Consultation. Geneva, World Health Organization (WHO), 2003 (16)
From this report, on page 90 (100 of 160): "Adequate dietary intake of potassium lowers blood pressure and is protective against stroke and cardiac arrythmias. Potassium intake should be at a level which will keep the sodium to potassium ratio close to 1.0, i.e. a daily potassium intake level of 70-80 mmol per day. This may be achieved through adequate daily consumption of fruits and vegetables."
Why close to 1.0? Where is the exact (original) reference of this statement? Has it any traces of strength of evidence? From where did they pick this ratio out? I never saw such ratio in scientific literature and in mature human milk. Only in the colostrum is this molar ratio close to one to one, but this has an evolutionary explanation. The WHO misleads all of the humanity. This is not science, but charlatanry. This is a typical pseudo-scientific method. How this may have been made again, in 2013? Five decades, and what did the scientific elite do meanwhile? And what they do now? Really, the progress of the science has been stopped! Global corruption and global censorship? I notice it; the 10th edition of RDA (1989) recommended for an adult 500 mg/day sodium. (17) And this was the best recommendation, but now this is ignored. So, the WHO recommend now for an adult 2 g/day of sodium and at least 3510 mg/day potassium. This excess sodium and the wrong Na/K ratio increases the entropy, and the (aerobic and anaerobic) energy consumption of sodium-potassium pump, and is fourfold - fivefold sodium load on the kidney. In Hungary, the real sodium intake could be 6-8 g/day! I know a "very good job", it's just the work of 4-5 men, or just of 12-20 men, day by day, until die. Are there volunteers?

Conclusions
In the health sciences it is not allowed to ignore the laws of the physics and the chemistry. We must use the already existing, ignored (forgotten or censored) knowledges, and we must to teach that to everybody. This is the duty of the scientific elite. The fats and the sugars are foods, and are sources of our energy. The excess sodium intake (above the optimum) and the extremely wrong ratios of metals enhance the entropy, and the entropy devours our energy. Our vital processes (functional processes of the cells) receive less energy, because our metabolic rate is limited. All of our organs and vital processes work worse. Consequently, the unnecessary sodium excess increases the incidence of all illnesses without any exception. Increase of physical activity doesn't save us (since, we hasn't enough energy to do it). Reducing the fat and sugar content of processed foods doesn't save us. The sonorous "reducing salt intake" programs doesn't help us. Only one solution exists. We must radically reduce the sodium(-chloride) content of processed foods, not by taxes, but by strict laws. On the other hand, it is necessary to reduce the tax of the spices and his price. The salt is the greatest blunder of the Homo Sapiens. Only the man nourishes the entropy in his own body. There are not free-living animals like this on this Earth. The entropy and the natural selection destroyed the such species. (The natural selection already has little effect to human genome, does not repair it already.) The salted humanity genetically degenerates and will be idiotic. We must stop the putting salt. Otherwise - our fiercest enemy - the entropy destroys us.

References:
1. Oregon State University, Linus Pauling Institute, Micronutrient Information Center, Sodium (Chloride)
http://lpi.oregonstate.edu/infocenter/minerals/sodium/
2. DIETARY REFERENCE INTAKES http://www.nap.edu/catalog/dri/
3. Saulo Klahr and Neal S. Bricker: Energetics of Anaerobic Sodium Transport by the Fresh Water Turtle Bladder. J Gen Physiol. 1965 March 1; 48(4): 571-580 http://europepmc.org/articles/PMC2195440/pdf/571.pdf
4. Alex G. Therien and Rhoda Blostein:INVITED REVIEW - Mechanisms of sodium pump regulation. Am J Physiol Cell Physiol September 1, 2000 vol. 279 no. 3 C541-C566 http://ajpcell.physiology.org/content/279/3/C541.full
5. Christopher B Scott: Review, Contribution of anaerobic energy expenditure to whole body thermogenesis. Nutrition&Metabolism 2005, 2:14 http://www.nutritionandmetabolism.com/content/2/1/14
6. Shaun F. Morrison, Kazuhiro Nakamura and Christopher J. Madden: Central control of thermogenesis in mammals. July 1, 2008 Experimental Physiology, 93, 773-797. http://ep.physoc.org/content/93/7/773.full
7. Henningsen N.C.: The sodium pump and energy regulation: some new aspects for essential hypertension, diabetes II and severe overweight. Klinische Wochenschrift 63 Suppl 3:4-8. 1985. http://www.ncbi.nlm.nih.gov/pubmed/2582182
8. Maiken Nedergaard, Steven A. Goldman, Smita Desai, and William A. Pulsinelli: Acid-induced death in neurons and glia. The Journal of Neuroscience, August 1991, 11(8): 2489-2497 http://facweb.northseattle.edu/csheridan/Biology160_Win11/pdfs/Flow%20of...
9. Toshimasa Osaka, Akiko Kobayashi, and Shuji Inoue: Thermogenesis induced by osmotic stimulation of the intestines in the rat. J Physiol. 2001 April 1; 532(Pt 1): 261–269. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2278526/
10. Ram K. Mathur: Role of diabetes, hypertension, and cigarette smoking on atherosclerosis. J Cardiovasc Dis Res. 2010 Apr-Jun; 1(2): 64–68. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2945206/
11. Meneton P, Jeunemaitre X, de Wardener HE, MacGregor GA.: Links between dietary salt intake, renal salt handling, blood pressure, and cardiovascular diseases. Physiol Rev. 2005 Apr; 85(2):679-715. http://www.ncbi.nlm.nih.gov/pubmed/15788708 http://physrev.physiology.org/content/85/2/679.long
12. Kacie M Dickinson, Peter M Clifton, and Jennifer B Keogh: Endothelial function is impaired after a high-salt meal in healthy subjects. Am J Clin Nutr March 2011 vol. 93 no. 3 500-505 http://ajcn.nutrition.org/content/93/3/500.full
13. Sandor Z.: Equivalency law in the metal requirement of the living organisms. Acta Alimentaria 27 (4): 389-395. 1998.
http://padre.uw.hu/ekvis/eqlaw.htm
and in hungarian: http://padre.uw.hu/ekvis/ekvitorv.html
14. Yamawaki N, Yamada M, Kan-no T, Kojima T, Kaneko T, Yonekubo A.: Macronutrient, mineral and trace element composition of breast milk from Japanese women. J Trace Elem Med Biol. 2005; 19(2-3): 171-81. Epub 2005 Oct 24. Source Nutrition Research Institute, Meiji Dairies Corporation, 540 Naruda, Odawara, Kanagawa 250-0862, Japan.
http://www.ncbi.nlm.nih.gov/pubmed/16325533 http://www.sciencedirect.com/science/article/pii/S0946672X05001008
15. WHO issues new guidance on dietary salt and potassium http://www.who.int/mediacentre/news/notes/2013/salt_potassium_20130131/en/ http://www.who.int/entity/nutrition/publications/guidelines/sodium_intak... http://www.who.int/entity/nutrition/publications/guidelines/potassium_in...
16. WHO Diet, nutrition and the prevention of chronic disease. Report of a Joint WHO/FAO Expert Consultation. Geneva, World Health Organization (WHO), 2003 http://whqlibdoc.who.int/trs/WHO_TRS_916.pdf
17. Recommended Dietary Allowances 10th ed., National Academy Press, NW, Washington DC. 1989 http://www.nap.edu/openbook.php?isbn=0309046335
More related references: http://padre.uw.hu/ekvis/entropyobesity.htm
Zoltan SANDOR
Institute of Materials and Environmental Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences
E-mail: sandor.zoltan @ ttk.mta.hu http://www.ttk.mta.hu/en http://padre.uw.hu/index.html