by Charles Weber, MS

Sodium and are proposed to be regulated by varying secretion of aldosterone, DOC, 18 OH-DOC, and 16 alpha 18 dihydroxy 11 deoxycorticosterone in response to the nutritional load. The first two steroids are for high potassium and the second two for low potassium intake, the potassium effects of the third indirect via affects on hydrogen ion (acidity). The first and third steroids are for low sodium intake.

You may find useful for definitions and easy to use a search for abstracts of journal references, "Gateway".

INTRODUCTION

Examination of the results of past experiments on the mineralocorticoid hormones seems to say that they exert their control over kidneys for the purpose of keeping blood serum sodium and potassium content constant through at least three and possibly four or more steroid hormones. I believe that aldosterone's role is fairly clear, and well accepted. The others are largely speculations of mine.

The three discussed here, besides aldosterone (also called aldocorten, aldocortene, aldocortin, electrocortin, or elektrocortin) are deoxycorticosterone (also called cortexone, 11 desoxycorticosterone, deoxycortone, desoxycortone, compound B, DOCA, or DOC), 18 hydroxy 11 deoxycorticosterone (also designated 18 OH-DOC), and 16 alpha 18 dihydroxy 11 deoxycorticosterone which I will designate DOH-DOC.

They all must conserve sodium in order to be called a mineralocorticoid. Sodium makes up most of the cations of blood plasma at 145 milliequivalents per liter (3345 milligrams) and potassium makes up most of the cell fluid at about 150 millequivalents per liter (4800 milligrams). Plasma is filtered through the glomerulus of the kidneys in enormous amounts, about 180 liters per day [Potts p261]. Thus 602,000 milligrams of sodium and 33,000 milligrams of potassium are filtered each day. All but the 1000-10,000 milligrams of sodium and the 1000-4000 milligrams of potassium likely to be in the diet must be reabsorbed. Sodium must be reabsorbed in such a way as to keep the blood volume exactly right and the osmotic pressure correct; potassium must be reabsorbed in such a way as to keep serum concentration as close to 4.8 mEq [Lans] (about 190 milligrams) per liter as possible. Therefore, the sodium pumps must always operate to conserve sodium. Potassium must sometimes be conserved also, but since the amount of potassium in the blood plasma is very small and the pool of potassium in the cells is thirty times as large, the situation is not so critical for potassium. Since potassium is moved passively [Bennett] [Solomon] in counter flow to sodium in response to an apparent (but not actual) Donnan equilibrium [Kernan p40, 48] the urine can never sink below the concentration of potassium in serum except sometimes by actively excreting water at the end of the processing. Potassium is secreted twice and reabsorbed three times before the urine reaches the collecting tubules [Wright]. At that point, it usually has about the same concentration as plasma with respect to potassium. If potassium were removed from the diet, there would remain a minimum obligatory kidney excretion of about 200 mg per day when the serum declines to 3.0-3.5 mEq/1 in about one week, [Squires] and can never be cut off completely. Because it cannot be cut off completely, death will result when the whole body potassium declines to the vicinity of one-half full capacity. At the end of the processing, potassium is secreted one more time if the serum potassium is too high.

The potassium moves passively through "gates" (cell wall pores) and probably through one of the cell wall pumps which also pumps sodium, three sodium ions for each two potassium ions.. Even so, the net apparent effect is active in the tubules. When ions move through pumps there is a gate in the pumps on either side of the cell wall and only one gate can be open at once. As a result 100 ions are forced through per second. Pores have only one gate and there one kind of ion only can stream through at 10 million to 100 million ions per second [Gadsby]. For a diagram of how the potassium pores are viewed currently, see Miller’s article [Miller]. In order to open the pore requires calcium [Jiang] although it is thought that the calcium works in reverse by blocking at least one of the pores [Shi (has detailed pictures of the atoms in the pump) ] Carbonyl groups inside the pore on the amino acids mimics the water hydration that takes place in water solution [Zhou] by the nature of the electrostatic charges on four carbonyl groups inside the pore [Noskov]. In addition to the kidneys, the gastric glands, salivary glands, colon, perspiration glands, and maybe the red cells are target organs for the mineralocorticoids [* Turner?]. These physiological processes are controlled by members of the voltage-gated ion channel protein superfamily. This protein super family of 143 members is one of the largest groups of signal transduction proteins. Each member of this super family contains a similar pore structure. Eight families are included in this protein super family—voltage-gated sodium, calcium, and potassium channels; calcium-activated potassium channels; cyclic nucleotide–modulated ion channels; transient receptor potential (TRP) channels; inwardly rectifying potassium channels; and two-pore potassium channels. It is not a good idea to put a strain on these complicated pores that could be avoided by proper nutrition.

DISCUSSION

I believe I now see how the regulation of sodium and potassium is organized by the mineralocorticoids.

CASE #1: Sodium Intake Is Low; Potassium Intake Is High.

Aldosterone has been shown to be the primary steroid used to control the force and direction of the pumps under this circumstance. When potassium in the serum is higher than 4.8 mEq/1, the zona glomerulosa [Brown] of the adrenal jacket secretes more aldosterone [Lans] and potassium is excreted into the end of the tubules and the collecting ducts [Peterson & Wright]. Aldosterone also increases potassium out flow in the last part of the colon only [Fraser 1971] and increases sodium absorption throughout the colon. In the first part of the colon chloride enters with the sodium while in the last part there is only a potassium - sodium exchange [Dolman]. All this was in rats which make poor experimental animals as discussed below. The amount of aldosterone secreted is a direct function of the serum potassium [Bauer & Gauntner] [Linas] as probably determined by sensors in the carotid artery [Gann , Cruz & Casper], pressure in the carotid artery [Gann, Mills, & Bartter], the inverse of the sodium intake as sensed via osmotic pressure [Schneider], anxiety [Vening], and of the angiotensin II formation [Brown][Dluhy][Williams & Dluhy], which last is a peptide hormone for increasing blood pressure by constricting the arteries just ahead of the capillary bed [Haddy]. Angiotensin II is regulated by the renin (a peptide hormone) from the kidneys. Depletion of either potassium [Albrecht] or sodium activates secretion of renin, but in potassium depletion aldosterone is suppressed [Sealed]. If blood pressure has to be increased by constricting capillaries, which is what angiotensin II does, it is an indication that the body needs more sodium in order to expand blood volume or more potassium to strengthen the heart beat. That is undoubtedly the reason why angiotensin is involved in regulating aldosterone and is the core regulation [Williams & Dluhy]. Sodium restriction sensitizes aldosterone to angiotensin, but not 18hydroxy-corticosterone to angiotensin [Fraser 1978, p282]. Angiotensin II acts synergistically with potassium, and the potassium feedback is virtually inoperative when no angiotensin II is present [Pratt]. A portion of the regulation resulting from angiotensin II must take place indirectly from decreased blood flow through the liver due to constriction of capillaries [Messerli, PT]. When the blood flow decreases so does the destruction of aldosterone by liver enzymes. This may be one of the advantages of getting sufficient exercise. However, the primary regulation is acting directly on aldosterone production because angiotensin II acts synergistically with potassium, and the potassium feedback to aldosterone is virtually inoperative when no angiotensin is present [Pratt][Williams & Dluhy]. Such an arrangement tends to be fail safe. If anything happens to send the blood pressure spiraling upward out of control, when angiotensin II drops out in order to correct the situation, it leaves behind a somewhat enhanced potassium serum concentration which also tends to reduce pressure at serum contents of potassium [Haddy] above 4.8 mEq/liter of potassium, and causes sodium to start to decline by the same failure to stimulate aldosterone.

ACTH, a pituitary peptide, also has some stimulating effect on aldosterone probably by stimulating DOC formation which is a precursor of aldosterone [Brown]. I suspect that this is an adaptation to inversely help protect the body during diarrhea assuming that the primary purpose of ACTH is to inversely mobilize the body's defenses against potassium wasting intestinal disease [Weber 1998]. Aldosterone is increased by blood loss [Ruch p1099], pregnancy [Farrell], and possibly by other circumstances such as physical exertion, endotoxin shock,, and burns [Glas & Vecsei p209]. The aldosterone production is also affected to one extent or another by nervous control which integrates the inverse of carotid artery pressure [Gann, Mills, & Bartter], pain, posture [Farrell], and probably emotion (anxiety, fear, and hostility) [Venning 1956, 1957](including surgical stress) [Davson p715] [Elman] to produce an unknown messenger hormone which stimulates aldosterone secretion [*]. It is possible that this hormone may now be known and may possibly be thrombin or trypsin. Regulation of aldosterone is extremely complicated. I suspect the main reason why emotion is factored in, especially anxiety, is that the aldosterone operates by diffusing to the nucleus to produce a messenger RNA and the various steps take about an hour to come completely on stream [Sharp]. Thus, there is an advantage in an animal anticipating a future need from interaction with a predator since too high a serum content of potassium has very adverse effects on nervous transmission [Rechcigl]. Anxiety's effect can be discordant. People with an anxiety neurosis can have as high as four times the secretion as normal and people with schizophrenia have a low secretion [Lamson]. This circumstance may be a large part of the affect that placebo manipulation has on experiments.

This system has been well studied and its major features are not subject to much doubt. Potassium feedback is the main regulation of aldosterone in normal diet and health, and the other features of aldosterone's regulation are for the purpose of fine tuning and forestalling future circumstances.

The slope of the response of aldosterone to serum potassium is almost independent of sodium intake [Dluhy]. Aldosterone is much increased at low sodium intakes, but the rate of increase of plasma aldosterone as potassium rises in the serum is not much lower at high sodium intakes than it is at low. Feedback by aldosterone concentration itself is of a non morphological character (that is other than changes in the cells' number or structure) and is poor so the electrolyte feedbacks predominate short term [Glaz & Vecsei]. Thus, the potassium is strongly regulated at all sodium intakes by aldosterone when the supply of potassium is adequate, which it usually is in primitive diets. Aldosterone averages 10 times as high or so among Yanomamo South American Indians as people in our society because their potassium intake averages four times as high and sodium is much lower [Oliver]. On the other hand, if a low potassium diet is fed, the aldosterone declines 5 times in only 24 hours and potassium excretion in the tubules virtually stops in 2 days, by stopping of secretion the first 24 hours and after that by reabsorption caused by low cell content within 72 hours [Linas] The known stimulation by aldosterone of the sodium pump which secretes potassium into the distal loop of the tubules [Stanbury], along with the nature of the potassium feedback already mentioned, make aldosterone certainly a hormone for unloading potassium. As much as 26 grams of potassium can be unloaded per day by healthy people accustomed to a large intake [Peterson CG]. Aldosterone is heavily relied on during high plasma potassium for the aldosterone secretion rises seven fold between 5 milliequivalents and six milliequivalents of potassium in the blood [Braley]. That aldosterone amount makes available the sodium in the bones, which contain nearly half the body's sodium, and is circumstantial evidence that the body depends considerably on aldosterone to keep the serum sodium retained and normal [Davson p717]. Aldosterone keeps the sodium and potassium normal in mononuclear leucocytes [Wheling].

The interrelation of aldosterone with peptide protein hormones is rather complicated. For instance, alpha-melanocyte-stimulating hormone (alpha-MSH) stimulates aldosterone but is itself changed by other peptide proteins (this is a full text site). Perhaps the reader can untangle these relationships to the end of yielding useful health and nutritional strategies.

The question is "What hormones are involved when a different diet or disease makes necessary a different excretion pattern?" I suggest that at least three other mineralocorticoids may be involved. Aldosterone is designated CASE #1.

CASE #2: Sodium Intake Is High; Potassium Intake Is High.

Such a case would obtain when well fed primitive humans have a clam bake or find a salt lick. It is still necessary to unload potassium, but sodium retention must be less strenuous. I suspect that DOC (deoxycorticosterone) is used for this purpose. DOC stimulates the collecting tubules (the tubules which branch together to feed the bladder) [O'Neil] to continue to excrete potassium in much the same way that aldosterone did but not like aldosterone in the end of the looped tubules (distal) [Peterson & Wright]. At the same time it is not nearly so rigorous at retaining sodium as aldosterone [Ellinghaus], more than 20 times less. DOC accounts for only 1% of the sodium retention normally [Ruch]. In addition to its inherent lack of vigor there is an escape mechanism controlled by an unknown non steroid hormone [Pearce] which overrides DOC's conserving power after a few days just as aldosterone is overridden also [Schacht]. This hormone may be the peptide hormone kallikrein [Majima], which is augmented by DOC and suppressed by aldosterone [Bonner]. If sodium becomes very high, DOC also increases urine flow [O'Neil]. DOC has about 1/20 of the sodium retaining power of aldosterone [Oddie] and is said to be as little as one per cent of aldosterone at high water intakes [Desaulles]. Since DOC has about 1/5 the potassium excreting power of aldosterone [Oddie] it probably must have aldosterone's help if the serum potassium content becomes too high. DOC's injections do not cause much additional potassium excretion when sodium intake is low [Bauer & Gauntner]. This is probably because aldosterone is already stimulating potassium outflow. When sodium is low DOC probably would not have to be present, but when sodium rises aldosterone declines considerably, and DOC probably tends to take over.

DOC has a similar feedback with respect to potassium as aldosterone. A rise in serum potassium causes a rise in DOC secretion [Brown], which is the correct response for this thesis. However, sodium has little effect [Schambelan & Biglieri], and what effect it does have is direct [Oddie]. Angiotensin (the blood pressure hormone) has little effect on DOC [Brown], but DOC causes a rapid fall in rennin, and therefore angiotensin I, the precursor of angiotensin II [Grekin]. Therefore, DOC must be indirectly inhibiting aldosterone since aldosterone depends on angiotensin II. Sodium, and therefore blood volume, is difficult to regulate internally. That is, when a large dose of sodium threatens the body with high blood pressure, it cannot be resolved by transferring sodium to the intracellular (inside the cell) space. The red cells would have been possible, but that would not have changed the blood volume. Potassium, on the other hand, can be moved into the large intracellular space, and apparently it is by DOC [Grekin] in rabbits since DOC injections lowered serum potassium but did not alter excretion. Thus, a problem in high blood potassium can be resolved somewhat without jettisoning too much of what is sometimes a dangerously scarce mineral and a mineral which reduces the force of the heart during a deficiency. Movement of potassium into the cells would intensify the sodium problem somewhat because when potassium moves into the cell, a somewhat smaller amount of sodium moves out [Rubini]. Thus, it is desirable to resolve the blood pressure problem as much as possible by the fall in rennin above, therefore avoiding loss of sodium, which was usually in very short supply on the African savannas where human ancestors probably evolved.

At the same time dangerous problems with low blood potassium can be avoided somewhat because DOC inhibits glycogen formation [Bartlett], so at low potassium intakes glucose surges are less likely to cause low blood potassium. The resemblance of the pattern of the electromotive forces produced by DOC in the kidney tubules to normal potassium intake, and the total dissimilarity of their shape as produced by potassium deficient tubules, [Helman & O'Neil] would tend to support the above view. The above attributes are consistent with a hormone which is relied upon to unload both sodium and potassium.

DOC's action in augmenting kallikrein, the peptide hormone thought to be the sodium "escape hormone," and aldosterone's action in suppressing [Bonner][Wright & Davis] it is also supportive of the above concept.

ACTH has more effect on DOC than aldosterone. I suspect that this is to give the immune system control over the electrolyte regulation during diarrhea [Weber 1998] since during the dehydration that diarrhea produces, aldosterone virtually disappears any way [Merrill] even though rennin and angiotensin rise high. It is for this loss of aldosterone reason that potassium supplements are very dangerous during dehydration and must not be attempted until at least one hour after rehydration. DOC's primary purpose is to regulate electrolytes. It has other effects on copper enzymes, proteins and connective tissue which I believe is used by the body to help survive during potassium wasting intestinal diseases. Most of the DOC is secreted by the zona fasciculata of the adrenal cortex which also secretes cortisol, and a small amount by the zona glomerulosa which secretes aldosterone.

The greater efficiency of DOC in permitting sodium excretion (or perhaps it should be expressed as inefficiency at retention) must be partly through morphological changes in the kidney cells because escape from DOC sodium retention takes several days to materialize, and when it does, these cells are much more efficient at unloading sodium if sodium is then added than cells accustomed to a prior low intake [*]. Thus, paradoxically, a low salt intake should be protective against loss of sodium in perspiration. Progesterone prevents some of the loss of potassium by DOC [Wambach]. Maybe this is related somehow to the resurgence of arthritis that sometimes happens after pregnancy is over.

CASE #3: Sodium Intake Is Low; Potassium Intake Is Low.

Someone living on the African savanna, profusely perspiring and confined to eating nuts, or worse yet nothing at all, could find himself in this situation. When potassium becomes low, the first thing that happens is that excretion of potassium from the far end of the kidney tubules and collecting tubules declines. This happens within 24 hours and virtually stops in 2 days. [Bauer & Gauntner]. The large decline in aldosterone secretion [Bauer & Gauntner] is undoubtedly a large part of it. However, it is still necessary to rigorously conserve sodium, and I tentatively propose that this is the function of 18 OH-DOC. I have no direct evidence for this yet, but there is strongly suggestive circumstantial evidence. Under low sodium intake 18 OH DOC is increased in serum [Williams, Braley & Underwood]. There is a marked increase in serum 18 OH DOC after injection of insulin [Sparano] [Hiatt] and this may be due to the hypokalemic (low serum potassium) tendency after a rise in insulin [Flatman] which in turn would make the serum more acidic.

18 OH-DOC lowers urine pH but has no affect on potassium excretion [Nicholls][Damasco]. This would seem to indicate that 18 OH-DOC's primary purpose is to stimulate hydrogen ion or ammonium excretion. If so, its use by the body to conserve potassium would be indirect by virtue of hydrogen ion's interference with potassium excretion and perhaps strongly dependent on the potassium cell or plasma content, because in potassium deficient rats markedly less 18OH DOC is converted to 18OH corticosterone and less yet if sodium is deficient [Muller]. It would also hint that the large affect that ACTH has on 18OH DOC, causing 18OH DOC to go down to zero when ACTH does [Tan], revolves primarily around keeping serum immune enzymes at a low pH (high acid) during infection by inhibiting 18OH DOC’s secretion upon declining, and therefore also acid excretion. It probably is important normally to keep the vacuoles where pathogens are digested at a high pH because if the pH or alkalinity is not high enough, the pathogens inside the cells are not digested [Ahluwalia]. So when an intestinal or other disease is not calling for ACTH to decline, the potassium conserving attribute of 18OH DOC by virtue of stimulating acid excretion may be valuable. Perhaps additional experimentation will cast some light on 18 OH-DOC.

Insulin is used by the body to counter high serum potassium only at low potassium intakes. At high intakes the affect of insulin stays normal [Knochel]. Thus insulin would help correct surges in serum potassium without the body losing potassium during low intakes.

It is possible that the 18OH DOC does not act directly on electrolytes, but, in addition to the above hydrogen ion affect, through a synergistic or blocking action on other hormones. I suspect that 18 OH DOC acts primarily by blocking aldosterone's effect on potassium, and must have aldosterone to assist it with sodium. Nichols, et al, have been able to show that injection of 18 OH-DOC, which raised blood levels of this hormone ten times, were more retentive of sodium than a similar amount of aldosterone. So there must be a synergism involved. At the same time, the ratio of sodium to potassium excretion declined very little for 18 OH-DOC, while for aldosterone, the ratio fell to as little as 1/3 that of control men [Nichols 1966]. This implies a considerable sparing of potassium by 18 OH-DOC. If the original aldosterone could have been removed from the serum first, it is possible that the difference would have been greater yet.

Angiotensin II has very little effect on 18 OH-DOC [Melby 1976] and is ambiguous nor does serum potassium above 4.8 mEq/litter (187 mg) [Biglieri & Lopez].- This last is not surprising since 18 OH DOC should not be used by the body at high serum potassium. Under low sodium intake, 18 OH-DOC rises in the serum [Williams GH], which is the correct response for the proposed purpose. ACTH causes a marked increase in 18 OH-DOC [Moore] up twenty fold [Melby, Dale & Wilson], probably by a generalized affect on the zona fasciculata of the adrenal cortex where 18 OH-DOC is synthesized. I believe that the decline in 18 OH-DOC when ACTH declines implied by this is part of the defense against diarrhea already mentioned because of the dehydration that ensues then and the need to preserve osmotic pressure by unloading sodium. Also it is possible that it is also related to a necessity of immune enzymes to operate more vigorously at higher pH (lower acidity). Large amounts of ACTH have a greater affect on 18 OH-DOC than on cortisol [May]. When ACTH drops to zero, 18 OH-DOC does also [Tan]. I have not seen evidence so far that cholera enterotoxin, or any other aspect of digestive disease except dehydration [Aguilera] directly affects ACTH yet. If this hypothesis is correct, some aspect of diarrhea should affect ACTH.

More important to know would be the effect of 18 OH-DOC has on angiotensin II because at low serum potassium situations, the intracellular (inside the cells) potassium is usually decreased and this depresses heart contraction. I suspect that 18 OH-DOC will be found to stimulate angiotensin II rather than the reverse if it has an affect because the intracellular potassium is much more important than serum potassium on the strength of heart contractions [Libretti][Biglieri & Lopez]. So when heart contraction strength decreases from low potassium status, it should be imperative to contract the capillaries in order to make sure that blood pressure does not drop. This is likely because the relaxation of capillaries by potassium between 4 and 8 mEq/l serum content [*] is some kind of an adaptive circumstance rather than an inherent characteristic of pre capillary blood vessels. Whether the above stimulation has evolved or not, I don't know since I know of no experimental data. However angiotensin II apparently does cause a drop in 18 OH-DOC [Williams GH] which might be a negative feedback kind of phenomenon. If this hunch is correct, the low sodium status in this case would reinforce its evolution because low serum sodium's effect on volume also decreases blood pressure. While direct evidence is not available to me, it has been demonstrated that there is more of a marked rise in rennin and therefore angiotensin II at low potassium intake than at any other electrolyte status [Douglas]. In any case, 18 OH-DOC is deeply involved in one of the three forms (at least) of hypertension [Melby 1972 p323].

It is possible that the steroid known as 19-Oxo-deoxycorticosterone is a steroid used by the body to prevent potassium excretion. It believe it would warrant further investigation.

CASE #4: Sodium Is High; Potassium Is Low.

Any of our progenitors who managed to find a salt lick, nothing but nuts or nothing at all would find themselves in this circumstance. Modern man eating only starchy, salty refined food would also be there. Someone with diarrhea would probably also be because the dehydration creates a serum artificially high in sodium concentration and because when water can't be absorbed in the lower intestinal tract, potassium can't be either and is lost. For this situation, I propose DOH-DOC. DOH-DOC increases the sodium to potassium ratio in urine slightly when injected into rats. This slight increase takes place even when small amounts of aldosterone are injected at the same time. That amount of aldosterone injected alone lowered the ratio slightly. [Fuller]. Unfortunately, rats are not good experimental animals for experiments on a hormone possibly used during diarrhea because rats have something in their digestive fluid which neutralizes cholera enterotoxin. [Donowitz]. Also, their ascending colon increases water absorption under c-AMP stimulation, opposite the effect in the descending colon and in other animals.[Hornyck]. Thus, the enterotoxin of diarrhea undoubtedly has much less effect on them. DOH-DOC combined with aldosterone is more retentive of sodium than aldosterone alone, while DOH-DOC does not retain sodium itself [Melby & Dale 1976] [Dale 1974]. DOH-DOC does not displace aldosterone in general. [Fuller]. DOH-DOC must act in conjunction with aldosterone. If both are secreted together, sodium would be drastically conserved. In other words DOH-DOC acts inversely to unload sodium. If aldosterone drops out, there would be a precipitous loss of sodium retention since DOH-DOC alone has no affect on sodium [Melby & Dale 1976] , while at the same time, if my contention is correct, potassium would cease to be excreted in the tubules. I suspect that DOH-DOC has its greatest effect on sodium in the colon because it is here where it would be most advantageous to unload sodium in order to keep water loss in the kidneys at a minimum. I know of no evidence for the colon effect. Its affect on potassium excretion would be most valuable in the kidneys, and this may be why it interferes with DOC's potassium excretion stimulation in the kidneys [Linas]. Conversion of 18 OH DOC to DOH-DOC is greatly increased in the kidneys of low renin patients [Melby & Dale 1977]. under such a circumstance sodium could be much more strongly retained as long as aldosterone was present and potassium more retained in any case. Not many experiments have been performed on DOH DOC, so more assured conviction that this is the hormone acting inversely for case #4 will have to wait, and there are no experiments to this date..

It may yet be found that angiotensin II or rennin do not increase DOH-DOC, but that DOH-DOC decreases angiotensin II in the vicinity of 4.8 mEq/l and then considerably increases it if the intracellular (cell interior) potassium becomes low. If the mechanism is such that both trends are not possible, then only the second should obtain, for in matters of regulation it is the extreme circumstances which should prevail if a compromise becomes necessary, those circumstances when an animal is fighting for its life.

When DOC is injected into people, it creates malaise, headache, loss of appetite, insomnia and muscle cramps [Relman & Schwartz]. It is possible that some of these symptoms are actually arising from increased internal secretion of DOH-DOC which may be resulting from retention of sodium and loss of potassium implied in the use of DOC injections. It is unlikely that the DOC is causing these symptoms directly because they do not appear when a diet high in sodium and potassium raises DOC in the body. The body may be using DOH-DOC to create some of those symptoms and feelings in order to help to protect it from excessive action during diarrhea. Some of the damaging effects of DOC injections on the heart [Melby, et al 1972] may arise this way also. The loss of appetite, if it exists, would be especially valuable during diarrhea.

If DOH-DOC is important during diarrhea as I suspect, it could be that ACTH inhibits it, and thus stimulates it upon ACTH's decline, or at least ACTH has no effect. I know of no information on this.

CONCLUSIONS

By secreting various ratios of the above steroids in conjunction with rennin, the angiotensins, ADH water retaining hormone, thirst and unknown supporting hormones, fairly accurate fine tuning should be possible of sodium, potassium, serum volume, osmotic pressure, hydrogen ion, and blood pressure. The cell status is maintained largely by controlling the serum [*].

I suspect that the distant ancestors of man evolved primarily as fruit, nut and leaf eaters of broad leafed plants, using meat as a fortuitous supplement. The tooth design is almost conclusive evidence of a herbivore, the salivary gland which dissolves starch is strongly suggestive of nuts, and the present day eating preferences of most people is supportive of broad leafed (dicotyledon) plants and seeds. Such a diet is low in sodium and fairly high in potassium [Abernethy]. If so, and I am right about the above, we are organized around aldosterone. I suspect that when we depart from this possibly ideal state for any length of time, we lay ourselves open to the statistical chance of degenerative diseases because our other physiological processes are geared to this hormone balance.

I suspect that Case #2 may be associated with the form of hypertension which is hard to reverse. The reason I suspect this is that DOC is associated with increased synthesis of collagen and it is possible this tends to increase the thickness of artery walls [Cox] with time and decrease their elasticity. The much greater tendency to grow excess connective tissue when foreign bodies such as silica are imbedded in the skin during DOC injections [Desaulles] [Pospisilova] would give circumstantial support to such an explanation.

Case #3 is probably furnishing some of the symptoms of rheumatoid arthritis since there is a consistently low whole body potassium content in this disease [LaCelle], aldosterone is low in arthritics [Cope & Llaurado], and personal experience is supportive [Weber 1974]. Indicative is that arthritis has been produced by DOC injections [Selye]. I have no information on the status of 18 OH DOC in arthritis. Anyway, it is probable that the bulk of the symptoms manifest themselves through cortisol status and its response modifying factors because this hormone is reduced in its secretion by the effect of low potassium on the zona fasciculata [Mikosha] and because cortisol removes many of the symptoms of arthritis. The amount of potassium to heal rheumatoid arthritis in adults must usually be 3500 milligrams/day or more because this is the amount which permitted slow improvement of a man across a three month time span [Clark], assuming his sodium intake was normal. Black people receive 1500 milligrams/day and white people 2000 milligrams/day in Georgia [Grim] which intake would probably not replenish potassium if diarrhea, vomiting, perspiration, or emotional stress caused a deficiency, since 2000 milligrams is less than the minimum daily requirement (MDR) for young adults. There is also circumstantial evidence from nutritional experiments using vegetables [Eppinger]. An unpublished experiment performed on eight subjects has revealed beneficial results from potassium supplements [Rudin MV, private communication]. Rastmanesh has performed an experiment testing potassium against rheumatoid arthritis with very encouraging results [Rastmanesh].

I suspect that most of the people who have rheumatoid arthritis, especially young onset, have had their kidneys damaged by poison or disease in such a way as to make them less efficient at retaining potassium or too efficient at excreting it. I suspect bromine gas as one possibility, for instance, since it probably affected me that way. Childers has proposed mild poisons in tomatoes, potatoes, egg plant, and peppers [Childers] as contributory, although it has not been established for sure to date. Some infectious diseases may have a similar effect. An unknown mycoplasma bacteria has been suggested as being involved, and may be the primary cause with potassium deficiency making it impossible for the body to kill the bacteria. In addition some people's immune system may be more sensitive to a potassium deficiency than others, possibly because of inappropriate secretion of one of the peptide hormones or less inhibition of cortisol.

Case #4 may prove to be associated with degeneration of heart and kidneys, but based primarily on nutritional statistics. It is also possible that case #4 plays a role in suppressed rennin hypertension, since there is increased secretion of DOH-DOC in all cases of that last disease [Melby & Dale 1976]. There is no evidence I know of that the DOH-DOC itself causes the damage. Drifting back and forth between case #3 and #4 may make one more susceptible to heart attacks and periarteritis nodosa, because arthritics have a low cell content to start with, so that this is superimposed on the harmful effects of high sodium intake, whatever they are, the situation could be much worse than when starting from a well nourished body. The higher death rate in arthritics from heart attacks is indicative. It seems that low serum potassium by itself in the absence of diuretics or poor kidney function is not a risk for heart disease. This may be because a potassium deficiency can not produce heart disease if vitamin B-1 is deficient at the same time. The large amounts of vitamin B1 fortified in our society no doubt contributes to the debacle because heart disease from low cell potassium is impossible when vitamin B1 is deficient also [Folis]. When arthritics finally die, the usual terminal events are heart attacks, infections, and ruptured blood vessels [Matsuoka]. We have become so accustomed to these distorted statistics, that we fail to perceive their oddity. Indians in El Salvador have a heart disease rate one per cent of ours [World Health Organization]. There is very little chance for such a wide disparity not to have an environmental cause, especially nutritional. A possible reason for the infection and ruptures are discussed in a copper article. How to increase copper in food may be seen here.

Pregnant women increase their DOC secretion 10 times by the end of the pregnancy [Parker 1980] and have a markedly higher secretion before the onset of menstruation [Parker 1981]. It may be that the larger secretion of progesterone which takes place at these times [Parker 1981] makes necessary the enhanced secretion of DOC by virtue of progesterone's interference with DOC's primary purpose [Gornall]. This erratic secretion may have something to do with the much larger rate of arthritis among women. It is not difficult to envision a problem if such large swings became even a little poorly regulated or had to handle odd electrolyte intakes of sodium and potassium.

Modern nutritional professionals are all convinced that potassium is adequate in all diets and that a deficiency never materializes except occasionally clinically. Past nutritional texts reflect this view both in the amount of space devoted to potassium and its content, which content will usually list only one of the many causes of a deficiency (for instance [Robinson] ). When potassium supplements are prescribed, they get around the discordance between their convictions and practice semantically by calling the supplements "salt substitutes”, "polarizing solutions”, "pharmaceutical effects”, "ORT salts (oral rehydration therapy for diarrhea)", or similar terms. A deficiency is further defined out of existence by defining the blood serum content is normal at a 4.2 mEq/liter when the actual figure is 4.8 [Scribner].

Nevertheless, there are numerous circumstances which can cause potassium to be ominously low in the diet or cause excessive excretion (with references). I have already mentioned diarrhea, the most common and dangerous circumstance in nature. Potassium supplements to babies brought mortality from a virulent strain of diarrhea from 35% to 5% [Darrow]. Numerous experiments have shown that potassium supplements are very important for recovery from heart disease [Kadaner]. It is not possible to produce heart disease in animals with any known poison unless potassium is also deficient [Prioreschi]. It is important to know whether the heart disease is caused by potassium deficiency or vitamin B-1 deficiency because heart disease cannot materialize in rats if both are deficient [Folis]. Therefore, it is probable that potassium supplements or a high potassium diet to a patient with the "wet" heart disease of beri-beri would kill him. This may be one of the reasons why results with potassium against heart disease have been statistically fuzzy in the past. It may be the reason why non steroidal anti inflammatory (NSAID) drugs are associated with increased risk of mortality in heart disease considering that they interfere with aldosterone degradation [Knights]. It is crucial to know what type of heart disease is involved.

Psychic stress stimulation of aldosterone, profuse perspiration, excessive vomiting, eating sodium carbonate or bicarbonate (because hydrogen ion is excreted at the same site as potassium), laxatives, diuretics, licorice, hyperventilating, enemas, shock from burns or injury, hostile or fearful emotions, and very high or low sodium intakes all increase potassium losses, some massively. All together would probably be lethal in a fairly short time. Reliance on grain (especially white flour) or fatty foods, boiling vegetables, use of chemicals (soft drinks, for instance) instead of food, and use of most processed foods including frozen and canned permit considerable reduction of intakes. So does the reduced appetite associated with a sedentary life.

To speak of potassium deficiency as an aberration when enormous numbers of people are affected by these circumstances is not logical. Even if a serious degenerative disease does not materialize, an adequate intake is desirable to forestall future disasters and to permit one to operate at optimum. Some of the manifestations of the placebo effect become understandable in light of the effect of emotions on hormones. However, we cannot always be assured of a placebo being available, certainly not on the firing line, but not even for that matter in the quiet of a hospital where even nurses can be testy at times.

While understanding the hormonal basis for electrolyte control will not always have a practical nutritional application, it is nevertheless important that it be well understood. Unless the medical establishment understands the physiological basis for nutritional strategy, it will never accept programs with any ardor based on vague nutritional statistics alone. Also, even if it did, some patients would slip through the cracks as we have seen in the potassium vs. vitamin B-1 interaction. Also, sometimes clinical intervention is essential for genetic or cancer malfunctions of the hormonal systems or to help correct massive assaults of poison or injury. It is well to realize clearly what is happening. The abandonment of aldosterone using DOC instead may not prove logical for all cases, for instance. Excess potassium is the main problem in metabolic shock [Fox], yet previous texts about shock did not even so much as mention potassium, and often do not stress it these days. Our nutritional strategy and even our philosophy of life is entwined with understanding hormones.

It is especially important that nutrition be established by experiment. Currently, every one in the medical establishment is convinced that potassium deficiency cannot be involved in rheumatoid arthritis, but this without an experiment ever having been performed. It simply is not possible to predict the outcome of an experiment with certainty without actually performing it. It would be desirable to determine the effect of every food common in commerce not only on arthritis, but on all the degenerative diseases. Some foods known to be poisonous to animals or have poisonous related species in the wild have been used for thousands of years without ever having been tested. This is undoubtedly due to a universal quasi religious conviction or instinct that foods our parents taught us to eat or taste good could not possibly be harmful. This is not necessarily the case. Such experiments could have another advantage in that they might uncover foods that have a beneficial effect. Even small effects would be worth knowing about. The above conviction (or instinct) is so strong that most people will not eat nutritious food if tastier, but less nutritious food is available. Their instincts override their intellect not only in their eating habits, but in their scientific efforts. These scientific efforts are further thwarted from pursuing nutritional investigations because medical science stresses pharmaceuticals and glamour theories [Forman].

EPILOGUE

The health of people in the USA is abysmal and a major part of it is poor nutrition. As the 12th century physician, trying to cure by diet before he administers drugs, said; “No illness that can be treated by diet should be treated by any other means" or as Hippocrates expressed it in 460 - 377BC; "If we could give every individual the right amount of nourishment and exercise, not too little and not too much, we would have found the safest way to health." It would seem that a healthy life style has been known for a long time. It is my belief that an unprocessed, unfrozen, not canned, high in vegetables diet would keep a large majority of people reasonably healthy and without the need for fad diets. 80% of Americans do not eat adequate vegetables, but even though 72% of Americans take vitamin or mineral supplements daily or sometimes [Sardi p148], their health is atrocious, especially old people..

I would suggest that a partial solution to the problem of poor potassium nutrition would be to place a tax on all food that has had potassium removed by food processors and completely fund all Medicare and workman’s compensation for injuries and disease that relate to rheumatoid arthritis, heart disease, and high blood pressure. This would also take the onerous tax burden now incurred for them and place it on the shoulders of those who cause the problem

The author, Charles Weber, has a degree in chemistry and a masters degree in soil science. He has researched potassium for 45 years, primarily a library research. He has cured his own early onset arthritis (33 years old). He has published articles on allied subjects in; The Journal of Theoretical Biology (1970, 1983), The Journal of Applied Nutrition (1974), Clinical and Experimental Rheumatology (1983), and Medical Hypotheses (1984, 1999).

Also, you can rate the efficacy of potassium at this site.

All printed rights to this article are reserved. Electronic rights are waived.

Email to; isoptera at att.net or 1 828 692 5816 (USA)

SOME LINKS TO HEALTH ARTICLES

. You may see here the way to acquire a very comprehensive book about potassium nutrition and physiology. It is called “POTASSIUM NUTRITION in Heart Disease, Rheumatoid Arthritis, Gout, Diabetes, Metabolic Shock (hyperkalemia), and High Blood Pressure”. The table of contents and the introduction are shown.

(For a summary of potassium and copper physiology)

. Purpose of cortisol -- . Copper nutrition and physiology -- Strategies for Chronic Fatigue Syndrome and Fibromyalgia -- There is an an article discussing cashew nuts to cure a tooth abscess Which might prove useful. -- There is evidence that cell phones can produce tumors. Using remote ear phones would seem to be a good idea.
-- There is also an article which proposes some speculation about diabetes.

There is a site that contains reviews of natural remedies for many diseases .

Fluoride in city water will cause fluorosis discoloration of teeth, weakened bones, damage to the kidneys and immune system, bone cancer and, worst of all, damage to the nerves resembling Alzheimer’s disease.

For a procedure that discusses tetrathiomolybdate for removing copper and thus preventing further solid cancer growth and Hodgkin’s, see this site. This might buy some time until you can persuade a doctor to try tumor necrosis factor or interferon or an opioid antagonist drug called Naltrexone (Naltrexone in the large 50mg size, originally manufactured by DuPont under the brand name ReVia, is now sold by Mallinckrodt as Depade and by Barr Laboratories under the generic name naltrexone) that blocks some endorphin receptors. Said blockage is thought to cause the body to temporarily secrete more endorphins, especially after midnight at night. These endorphins are thought to stimulate the immune system, and in particular to stimulate the TH-1 or type 1 antiviral response by decreased interleukin-4 and with increased gamma interferon and interleukin-2 and a simultaneous decrease of type 2 anti bacterial response [Sacerdote]. It appears to be especially effective for minimizing symptoms and retarding progression of multiple sclerosis (MS) (also see these sites hereand here and this site) It is said to have no known bad side effects at those doses other than stimulate the TH-1 or type 1 antiviral response by decreased interleukin-4 and with increased gamma interferon and interleukin-2 and a simultaneous decrease of type 2 anti bacterial response [Sacerdote]. There is also reports from an extensive survey in this site. I think some clinical studies on Naltrexone are in order, and it should not be a prescription drug. Though side effects appear unlikely, it is not proven over longer periods. If you try it (it is a prescription medicine in the USA), it seems likely that you should discontinue if you get a bacterial infection in view of its inhibition of antibacterial response. Dr. Bihari has shown promising results for a large percentage of his cancer patients.

Olive leaf extract has shown clinical evidence of effectiveness against a wide range of viruses, including AIDS [Bihari], herpes, and cold viruses. It sometimes produces a Herxheimer or pathogen die off symptoms (from effectiveness against bacteria?). There is evidence that it is synergistic (reinforce each other) with Naltrexone. There have been a few case histories of improvement in what were probably arthritis patients and CFIDS patients. The active ingredient is said to be oleuropein or enolate. There has been very little follow up research done on it.

. Also it has been found that curcumin in turmeric or curry powder will inhibit several forms of cancer, including melanoma. People who live in India where these spices are eaten, have one tenth the cancer elsewhere. Here is an article with anecdotal evidence for pressurized oxygen, zinc, vitamin B6, and vitamin C after head injuries. They also claim a fair percentage of prison inmates from psychiatric disorders after head injuries.
See this site for evidence of a correlation between magnesium deficiency and cancer. The taurate is proposed as the best magnesium supplement. Taurine or 2-aminoethanesulfonic acid is an acidic chemical substance sulfonated rather than carboxylated found in high abundance in the tissues of many animals (metazoa), especially sea animals. Taurine is also found in plants, fungi, and some bacterial species, but in far less abundance. It is an amine with a sulfonic acid functional group, but it is not an amino acid in the biological sense, not being one of the twenty protein-forming compounds encoded by the universal genetic code. Small polypeptides have been identified as containing taurine, but to date there has been no report of a transfer RNA that is specifically charged with taurine [from Wikipedia]. It is essential to babies. It has been found that supplements of the amino acid, taurine, will restore the abnormal electrocardiogram present during a potassium deficiency by an unknown mechanism. This information has been used in several case histories by George Eby to control a long standing type of cardiac arrhythmia called pre atrial contractions (PACs), a benign but irritating and nerve racking heart problem, with 2.5 grams of taurine with each meal. . Taurine is said to be low in the diets of vegetarians. The 2.5 grams recommended by the American Heart Association causes diarrhea in some people and should probably be reduced in those people. Taurine has been used for high blood pressure, migraine headache, high cholesterol, epilepsy, macular degeneration, Alzheimer’s disease, liver disorders, alcoholism, and cystic fibrosis, and depression. . Keep in mind that some people may have a genetic defect that limits the amount of taurine tolerated and that adequate molybdenum may desirable.

A site is available which shows. foods which are high in one nutrient and low in another (including calories). This last site should be especially useful for a quick list of foods to consider first, or for those who must restrict another nutrient because of a genetic difficulty with absorption or utilization

The very extensive USDA Handbook #8 may be seen here. To access the information you must press "enter" to search, and then divide Kcal into milligrams of potassium. This last table is very comprehensive, is used in search mode, and even lists the amino acids. There are also links in it to PDF types of printouts from the table for individual nutrients available here Just click on the “A” or “W” button for the nutrient you desire. A table that has already done the potassium calculation is here in descending concentration or in alphabetical order. There is a free browser called Firefox, which is said to be less susceptible to viruses or crashes, has many interesting features, imports information from Iexplore while leaving Iexplore intact. You can also install their emailer. A feature that lists all the URLs on a viewed site can be useful when working on your own site.

If you have Iexplore, there is a tool bar by Google that enables you to search the internet from the page viewed, mark desired words, search the site, give page rank, etc.

There is a free program available which tells on your site what web site accessed you, which search engine, statistics about which country, statistics of search engine access, keywords used and their frequency. It can be very useful.

All printed rights to this article are reserved. Electronic rights are waived.

.

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This article updated in Apil 2014.

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