High Potassium Foods

High potassium foods protect against hypertension, stroke, osteoporosis, and kidney stones. Potassium and bicarbonate precursors combine to protect against these problems. Together they provide food that is balanced for how the body works. The cells in the body perform multiple balancing acts continuously. The proper balance maximizes how well the cells’ molecules carry out their functions. There are two main balancing acts performed by all cells. The first one balances the electrical charge in the cell and the second one balances the pH (acidity) inside the cell.

Electrical Charge Balance

In order to balance the electrical charge, the cell balances sodium and potassium ions inside and outside the cell to keep the electrical charge at the appropriate level in the cell. In order to balance the acidity, the cell balances hydrogen ions (H⁺) to keep acidity at the correct level. Both the electrical charge and the acidity determine the shape of the molecules of the cell. The shape of the molecules determines how well the molecules and cell function.

Potassium and sodium determine the electrical charge. They are positively charged ions, called cations. They determine the charge across the cell membrane and across many of the interior membranes. This charge across the membranes influences many of the chemical reactions in our cells.

Acidity Balance

But what about the negatively charged ions (anions)? Positive and negative charges must be almost equal. There is strong evidence that these anions control the acidity of our blood, our cells, and our fluid between our blood and our cells.

This acidity surrounds protein molecules in our cells. It has a major influence on the proteins’ shapes. And a protein’s shape determines how well it functions. The levels of different anions (negatively charged ions) in our blood and in our cells are determined through mechanisms at work in our kidneys.

Humans produce acid as part of how the body functions. When we exercise, we produce a great deal of acid. But even at rest, normal cell processes produce a great deal of acid. Most of this acid is eliminated as carbon dioxide that is exhaled through the lungs. Each day 15,000 mmol of acid are eliminated in this way.

Volatile Acids

The acids leading to carbon dioxide are called the volatile acids. The way that the volatile acids are eliminated is by using the large buffer pool of bicarbonate in the blood to combine with the acid ions. Bicarbonate ions (HCO₃^–) are alkaline ions that combine with acid ions (H⁺) to form H₂CO₃, which degrades into carbon dioxide and water. The chemical reaction is H⁺ + HCO₃^– = H₂CO₃ = H₂O + CO₂.

Non-Volatile Acids

We also have acids in our bodies that are called non-volatile acids. They cannot be exhaled through the lungs. They come from our food, and they must be eliminated through the kidneys. 40 mmol of this type of acid are eliminated in the urine by making ammonium. 70 mmol are eliminated in the urine with titratable acids.

For you chemistry buffs, titratable acid is used differently here than it is in chemistry. It means the amount of NaOH to bring the urine pH back to 7.4. It measures the amount of H⁺ that is associated with non-bicarbonate buffers in the urine. These buffers are mostly phosphates, but also include sulfates and a few other anions.

So there is over 15,000 mmol of acid being neutralized each day. This consists of 110 mmol of non-volatile acids being neutralized and 15,000 mmol of bicarbonate being exhaled. With so much bicarbonate being used up every day, there must be a source to replace it.

Bicarbonate Replacement

There are two main sources that replenish bicarbonate in the blood stream. The two sources are the kidney and the diet. Bicarbonate is produced in the kidney when acid is excreted into the urine. This occurs in the alpha intercalated cells, discussed below. And the remainder of our bicarbonate comes from food in the form of bicarbonate precursors.

Bicarbonate Precursors

Bicarbonate precursors are molecules that our body turns into bicarbonate. The food precursors of bicarbonate are abundant in plants. There are many different precursors, but among the most common are citrate, lactate, acetate, and gluconate. Although you do not have to become a strict vegan to have an adequate supply of bicarbonate, you do need to eat enough plants to neutralize any excess acid that your kidneys cannot handle if you are to remain healthy. This will help keep your cells at the correct acid level (pH).

Model Of Electrical And Acidity Balance

A beautiful model now exists that tells us how sodium and potassium work together with bicarbonate to keep our levels of potassium, sodium and acid appropriate for cellular function. A recent review (1) of how chloride is conserved, and how bicarbonate is excreted in exchange for chloride, explains the most recently discovered piece of this model.

The first clues leading to this recent contribution came from a 1975 study of the Yanomami, a modern indigenous group in the Amazon (discussed in this post). The study showed that the Yanomami’s urine had a high potassium level, and a low sodium and low chloride level. This low chloride level gave recent researchers a clue about how chloride is preserved. The chloride level was so low that their urine had to be alkaline. But how could chloride be exchanged for alkaline ions?

At the time of the 1975 study, it was unknown how this happened. It was not known how chloride could be preserved when so little was eaten in the diet. The Yanomami only excreted 10 mmol of chloride per liter of urine, indicating that they conserved it a great deal. Westerners usually have 110 to 250 mmol of chloride per liter in the urine.

Pendrin

But recent studies have shown how chloride can be so highly conserved. The mechanism has been summarized in the review article (1) to be discussed today. A molecule that was described in 2004, named pendrin, was originally discovered in patients with a particular type of congenital syndrome involving the loss of hearing. Later pendrin also was discovered in cells in the kidney.

Researchers found that pendrin in the kidney conserves chloride by excreting bicarbonate into the urine. Pendrin is found in the beta intercalated cells in the distal convoluted tubule of the kidney. When chloride needs to be preserved and there is sufficient bicarbonate in the blood, pendrin in the beta intercalated cells will pull chloride from the urine into the cell in exchange for bicarbonate.

But pendrin is not the only character in this story. In the kidney there are other molecules (exchangers and transporters) that fine tune sodium, potassium and acidity. The exact interaction of all these molecules has yet to be determined. But the protective role of pendrin has been determined. And aldosterone also plays a role.

Aldosterone

A recent finding is that, just like it does in the balancing of sodium and potassium (discussed in this post), aldosterone has a major influence on blood acidity. It does this by affecting the exchange of chloride for bicarbonate in the kidney.

Aldosterone helps to keep the acid level of the blood optimal by affecting two types of cells located in the kidney. It affects the alpha intercalated cell and the beta intercalated cell.

But it affects them in different ways. Aldosterone stimulates the alpha intercalated cell to secrete more acid into the urine. It stimulates the beta intercalated cell to secrete more bicarbonate into the urine. In this way aldosterone is a major player in acid-alkaline balance in our bodies.

Aldosterone stimulates the alpha intercalated cell to excrete an acid ion, H⁺, into the urine in the form of ammonium. The alpha intercalated cell also excretes H+ as a titratable acid by attaching the H⁺ to phosphate or another negatively charged ion. When the cell does this, it manufactures a bicarbonate molecule, which it sends into the blood stream. But there is a limit to the conditions under which the cell can manufacture bicarbonate.

Kidneys’ Limits

When the urine acidity (pH) reaches 4.5 to 4.4, the kidneys are excreting as much acid (H⁺) as they can. At this pH the backflow of hydrogen ions (H⁺) into the blood stream equals the excretion of hydrogen ions into the urine. It can no longer manufacture bicarbonate. After the urine pH reaches 4.4 to 4.5, the body must find other ways to neutralize any acid it produces so that it can keep the blood pH at 7.4. It must pull bicarbonate or other acid neutralizing ions from stores in the body, such as bone.

Our Bodies Are Not Made For The Modern Diet

But unlike many modern humans, early humans did not have the problem of getting too little acid neutralizer in their diet. Early mammals, including humans, got a great deal of bicarbonate precursors in their diet, and could afford to throw bicarbonate away in exchange for chloride, which was much harder to get from the diet. They did not have to pull acid neutralizers from stores in the body. Their kidneys used pendrin in the beta intercalated cells to exchange chloride for bicarbonate.

Aldosterone stimulates the beta intercalated cell to produce more pendrin. Pendrin pulls chloride from the urine in exchange for bicarbonate. Voila – two problems solved at once. Chloride is kept in the body and the extra bicarbonate is expelled. The bicarbonate neutralizes acid molecules in the urine. The more bicarbonate excreted, the more alkaline the urine.

Potassium Accompanies Bicarbonate Precursors

Large amounts of potassium usually accompany bicarbonate precursors in food. The large amounts of potassium stimulate aldosterone secretion. Aldosterone, in turn, stimulates the beta intercalated cell to produce more pendrin. Thus, when potassium needs to be expelled and sodium conserved, bicarbonate is also expelled and chloride conserved.

So aldosterone is a critical molecule that helps get rid of extra potassium and extra bicarbonate while conserving sodium and chloride. Early mammals, including man, had difficulty getting enough sodium and chloride, because it was far less available in the diet than potassium and bicarbonate precursors. Aldosterone helped solve this difficulty.

Since potassium and bicarbonate precursors were readily available in the diet, there was no reason to conserve potassium and bicarbonate. These ions were expendable and were traded for the sodium and chloride ions that were harder to get.

Our bodies evolved to conserve sodium and chloride, and still have no way to get rid of excessive sodium and chloride. But our bodies are exquisitely fashioned to eliminate potassium and bicarbonate, since potassium and bicarbonate were always consumed in far greater amounts than sodium and chloride until the rise of processed food.

What It Means To You

So does this mean that your urine should be alkaline? And what would be the optimal pH of your urine? There are no definitive answers to these questions yet. But it does mean that your urine should probably not have a pH of 4.4 to 4.5, which is the lowest pH that the kidney can make.

If the pH is this low, it may mean that you are unable to sufficiently buffer the acidity of your blood stream with diet. You must pull buffers from other storage areas in the body, such as bone. When the pH is 4.5 you are flogging your kidneys when they are already working as hard as they can. They can do nothing more.

If the pH is above 4.5, all may be well. And if the pH is alkaline (greater than 7), it means you are definitely getting enough of the bicarbonate precursors and you can limit your sodium and chloride intake. Your kidneys have you covered.
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1. Effect of mineralocorticoids on acid-base balance. Wagner CA. Nephron Physiol. 2014;128(1-2):26-34. doi: 10.1159/000368266. Epub 2014 Nov 6.

There are genetic differences that may contribute to slight differences in blood pressure response to sodium and potassium intake. These genetic differences may vary among races. They may explain the difference among races in the diseases resulting from a poor sodium potassium ratio, such as hypertension and stroke. There are studies showing a higher rate of hypertension and stroke in African-Americans than in Caucasian Americans. Does a difference in the sodium potassium ratio explain the racial difference in hypertension, stroke and death rate? The study to be discussed today looked at the sodium potassium ratio of the diets of African-Americans and Caucasian Americans to see if the ratio explained the differences.

Sodium Potassium Ratio Study

In the publication (1) to be discussed, the researchers looked at the REGARDS study participants to look for a reason for racial differences in the United States in stroke. More African-Americans than Caucasians suffer strokes. Some studies have found that African-Americans get more sodium and less potassium in their diet. The researchers sought to find out whether this was the reason for the increased prevalence of salt sensitive hypertension and strokes in African-Americans.

The researchers looked at whether the dietary ratio of sodium to potassium (inverse of the potassium to sodium ratio that we prefer) was associated with the racial differences in salt sensitive hypertension, stroke and death. They used data from the REGARDS study. The researchers in the REGARDS study restricted participants to people who were older than 45 years of age at enrollment into the study. They collected data from history, physical examination and blood tests.

In addition to this data, the researchers in the present report phoned the participants, did home visits to measure blood pressure and to deliver a self-administered food questionnaire, which the participants filled out. The questionnaire was a food frequency questionnaire from which the researchers estimated the sodium and potassium intake. They followed the participants for a mean follow-up period of 4.9 years. The researchers obtained follow-up concerning health status, hospitalizations and death every 6 months during this period.

The original participant group had 30,000 participants, but this was reduced to just over 21,000 participants. A participant was eliminated if the food frequency data was not complete enough to evaluate or if the participant had an extremely high energy intake. The researchers divided the study population along racial lines and gender lines, and then into 5 groups based on the sodium potassium ratio.

Findings About Diet

The sodium potassium ratio of the diet was similar for blacks and whites in all 5 groups. In the lowest ratio group both races had approximately the same ratio of sodium to potassium, 0.56 (1.8 potassium to sodium ratio) for blacks and 0.57 (1.75 K:Na) for whites. In the highest ratio group blacks had a ratio of 1.36 (0.74 K:Na) and whites had a ratio of 1.18 (0.85 K:Na).

Findings About Disease

The researchers were able to show a significantly increased risk of death for both racial groups as the sodium potassium ratio increased. The highest ratio group had a 52% higher risk of death than the lowest ratio group. There also was an increased risk of stroke for both racial groups, but the increase did not reach significance. The highest ratio group had a 29% higher risk of stroke than the lowest ratio group.

However there was no significant racial difference in disease rates within each group having the same sodium potassium ratio. The researchers did not find a large difference in the prevalence of hypertension between the 2 races. Nor did they find a significant difference between races for stroke or death. Within each group, the sodium potassium ratio for one race was close to the ratio for the other race. This would imply that the dietary sodium potassium ratio was more significant than any genetic differences in determining hypertension, stroke or death from any cause.

Limitations Of The Study

When discussing the limitations of the study the researchers pointed out that because this was an observational study they could only show an association and not show causation. Another weakness of the study was that they used a food frequency questionnaire rather than using the urinary potassium and sodium values. It is well known that these questionnaires have approximately a 25% level of inaccuracy. Furthermore, people tend to under-report the sodium that they take in and over-report consuming foods that would be a source of potassium.

This reporting discrepancy was likely present in this study, since the ratio in the highest group was the only one not better than the ratio of the average American diet. When 4/5 of the population reports a better than average ratio, the reported ratio will appear to be better than it actually is. The true potassium sodium ratio will be smaller than the reported ratio (sodium potassium ratio will be greater than reported). This kind of error weakened the ability of the study to find the effect of the potassium sodium ratio.

What It Means To You

Despite this weakened ability, this study did find a significant difference in death rate corresponding to the sodium potassium ratio. So the study, despite an important weakness, supports an important principle. Even though you may have genetic differences that can result in a higher prevalence of hypertension, stroke, and cardiovascular disease, your risk of these diseases can be reduced by improving your potassium sodium ratio. In this particular study, both blacks and whites had a lower incidence of disease when they had an improved ratio, and their risk of death was significantly reduced.

So no matter what your race or genetics, there is still much that you can do as an individual to reduce your risk. As an individual you can reduce your risk of hypertension, stroke, and cardiovascular disease by changing your diet to include less sodium and more high potassium foods. To find links to tables of high potassium foods, click on the tab labelled “Links To Food Potassium Tables” at the top of the page.
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1. High sodium:potassium intake ratio increases the risk for all-cause mortality: the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. Judd SE, Aaron KJ, Letter AJ, Muntner P, Jenny NS, Campbell RC, Kabagambe EK, Levitan EB, Levine DA, Shikany JM, Safford M, Lackland DT. J Nutr Sci. 2013 Apr 23;2:e13. doi: 10.1017/jns.2013.4. eCollection 2013.

Doctors in practice are focused on treating hypertension. A growing number are interested in the cause of primary hypertension so they can prevent it. For several decades, studies on the cause of hypertension have focused on sodium. Only recently has the balance of potassium and sodium as a cause of hypertension been understood. Even so, the balance of potassium and sodium as a cause of hypertension has made its way into recent medical physiology textbooks. But it has not made its way into medical practice. The importance of this balance is not widely realized. And it is not discussed in many of the publications and studies in the medical literature. The majority of studies still focus on sodium. One such study is a recent study (1) that discusses the link of the kidney to blood pressure, and focuses on the kidney’s regulation of sodium. It mostly ignores potassium.

History

The relationship of the kidney to blood pressure has been known for many years. The first connection of the kidney to hypertension was the proposal of Richard Bright almost 200 years ago that abnormal urine production led to increased resistance in blood vessels, raising the blood pressure. Dr. Dahl in the 1960s bred hypertensive rats and showed how a high sodium diet made them hypertensive.

In the 1970s Dr. Guyton and associates showed the physiological link of the kidney with sodium. They showed that the kidney regulates the body’s fluid by responding to the pressure of the fluid that flows through kidney blood vessels. The kidney did this by matching urinary excretion of salt (sodium) and water with the dietary intake of salt and water. When you consume sodium it goes into the blood and carries water with it. This expands the amount of blood in the vessels and increases the pressure. A kidney responds to this increased pressure by excreting fluid. And one of the kidney’s mechanism to excrete fluid is the excretion of sodium, which carries fluid with it.

Kidney transplantations in rats, and then in humans, also supported the role of the kidney in hypertension. These transplantations showed changes in blood pressure according to the type of kidney transplanted. Dr. Dahl transplanted a kidney from a hypertensive rat into a rat with normal blood pressure and caused hypertension in the rat. He also transplanted a kidney from a normal blood pressure rat into a salt sensitive hypertensive rat and showed that the hypertension was reduced. Others have shown similar results by repeating these experiments in other types of hypertensive and non-hypertensive rats.

Kidney transplantation in humans has had similar results. A patient with resistant hypertension requiring a kidney transplant will have relief of the hypertension if the kidney transplant is from a patient without hypertension.

In the 1980s, Dr. Hall and associates showed that angiotensin II acted on the kidney to change blood pressure. Later it was shown that angiotensin II acts on the sodium channels in cells in the kidney tubule. Similarly, the effect of aldosterone on blood pressure was shown through various experimental procedures.

More Recent Work

Most recently it has been shown how aldosterone works at the molecular level within the kidney tubule cells. This important work shows how sodium and potassium interact with each other and with bicarbonate in the kidney to affect blood pressure. See our post here about how this is done. This specific work is not mentioned in today’s article, but the author does discuss some similar work showing that aldosterone promotes potassium excretion. This is the only discussion of potassium in the article.

There are also other cellular interactions in the kidney that influence blood pressure. Many of these interactions function by acting on the regulation of sodium and potassium. WNK genes are an example. WNK stands for With No K (K is not potassium, but is a short-hand symbol for lysine). WNK genes are part of a network of kinases. The network regulates sodium and potassium in kidney cells. WNK does this by regulating the sodium transporters that reabsorb sodium in the distal nephron of the kidney. By doing this it affects the balance of sodium and potassium inside and outside the cell, and thus affects the cell membrane potential. Affecting this balance affects blood pressure and can eventually result in hypertension.

Other publications adding to the basic model of fluid retention and sodium potassium balance have been studies looking at the collection of fluid (extracellular fluid) between blood vessels and cells of the body outside the kidney. One area that has been investigated is in the skin, where sodium is collected in a greater concentration that it is in the blood. Sodium collects here because of certain types of proteins found in the skin. These unique proteins allow a collection of sodium accompanied by less water than in other parts of the body. This skin collection may be involved with some of the unexpected fluctuations in total body sodium in blood pressure that occur over the long term. These fluctuations were previously unknown, but were discovered during studies to prepare for the Mars expedition.

Mars Helps Out

Physiological work being done on subjects in preparation for a trip to Mars is giving some excellent data and expanding our knowledge of how sodium balance occurs. Among the data being collected is the relationship of sodium intake and sodium excretion. These are long-term studies because of the expected length of the trip to Mars. One study was for 105 days and another for 205 days.

Among the many findings, the researchers have found that sodium will fluctuate from day-to-day even when the sodium intake is the same every day. This fluctuation follows an infradian pattern. An infradian rhythm is a rhythm that lasts longer than a circadian rhythm. Prior assumptions had been made that sodium and potassium balance occurred in a day. This was the reasoning behind spot and 24 hour urine collections. It was thought that a 24 hour collection would capture the amount of sodium consumed during those 24 hours.

There are a number of speculations on how this infradian pattern occurs, and these speculations are presently being investigated. This infradian pattern has led to interesting findings concerning the accuracy of urinary fluid collection. As discussed in a previous post, a collection of urinary sodium reflects the amount of sodium ingested the previous day only 50% of the time. For 75% accuracy, 3 days should be averaged. And for a 92% accuracy, 7 days would need to be averaged.

Immune Involvement

The article also discusses the potential of immune mechanisms being involved with hypertension. It discusses that there may be immune reactions that have separate, independent effects on blood pressure.

However in this case, it is difficult to distinguish cause from effect. Rather than immune reactions causing increased blood pressure, the immune reactions and increased blood pressure may both result from the cellular response to sodium potassium imbalance. As was discussed in the post on heart failure, cellular death from a poor potassium sodium ratio will lead to scar tissue because of an inflammatory response. In that case, the immune reaction was caused by the cell death that occurred from potassium sodium imbalance.

Small studies have been done that show immunosuppression will lower blood pressure in hypertensives who have rheumatoid disease. The article discusses the various cytokines (molecules involved in the immune response) and the various inflammatory cells that may affect blood pressure. These cells and molecules almost certainly are involved in end-organ damage. If the organ that is damaged by the inflammation is the heart, kidney or blood vessels, then blood pressure should be improved by suppressing the inflammation.

Studies show that damage in the kidney blood vessels looks like the damage in the heart discussed above. At the tissue level the vessels show an inflammatory response when examined under the microscope. This inflammatory response looks very much like the response that researchers have described in animal hearts with experimental hypertensive heart failure.

The present article has only a limited discussion of the role of potassium and the kidney in hypertension. And it does not try to integrate its discussion of sodium with a discussion of the known mechanisms of potassium on blood pressure. But the author does give an excellent overview of sodium’s effect on blood pressure. As the basic understanding at the cellular level of how sodium and how potassium perform within the cell becomes better known, it will be more and more difficult for clinical articles to claim harm to healthy individuals from a sodium intake of 1500 mg or 2300 mg.
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1. The inextricable role of the kidney in hypertension. Crowley SD, Coffman TM. J Clin Invest. 2014 Jun;124(6):2341-7. doi: 10.1172/JCI72274. Epub 2014 Jun 2.

Within the medical community there continues to be a debate about whether lower sodium consumption reduces cardiovascular mortality. The debate involves two schools of thought. The first is that the lower the sodium consumption, the lower the cardiovascular mortality. The other group feels that there is an association of sodium consumption with cardiovascular mortality that is U-shaped or J-shaped. At both the higher and lower ends of sodium consumption there is an increase in mortality. In the center portion, which approximately corresponds to the average present American consumption, there is the lowest mortality.

This debate has prompted better and better studies with better and better data. As the better data is reported the weight of evidence favors more and more the direct correlation. In other words, the lower the consumption of sodium, the less the cardiovascular mortality. This is probably because it improves the sodium potassium ratio, but potassium is rarely considered.

To support the U-Curve, one after another meta-analysis is repeated. There are many problems with the U-Curve argument. A recent meta-analysis (1) touting the U-curve prompted a commentary (2) that discussed the problems with the U-Curve argument.

Recent Meta-analysis

The recent meta-analysis that prompted the commentary included 25 prior studies. 23 of the studies were prospective cohort studies and 2 were randomized controlled trials. However there are several problems whenever a secondary examination is made of studies that are not designed for the purpose of the secondary study. In this case the studies were not designed to study the sodium cardiovascular disease interaction. This resulted in some standard methodologic challenges.

In the case of the 23 cohort studies, every study was a secondary examination of data collected for a purpose that differed from the purpose of the secondary study. The original studies were not designed to find the relationship of sodium intake and cardiovascular disease (CVD). They were designed to find answers to different questions. This means the quality of the original studies may have been excellent for the question they were designed to answer, but the quality was poor for answering the sodium-CVD question.

There are 3 main problems with the methods used for every secondary study of cohorts to analyze the relationship of sodium to CVD. For this secondary study, the meta-analysis, the 3 main problems are: 1. systematic bias in measuring sodium, 2. reverse causation, and 3. imprecise estimation of urinary sodium.

Systematic Bias

Whenever an original study is designed to study something besides the purpose of the secondary examination, the original study may be slanted so that the area being examined in the secondary study is not evenly distributed. This would result in systematic bias. A review of 31 independent sodium-CVD cohort studies found 3 to 4 issues with methods per study. These issues had the potential to alter the direction of the association in 96% of the studies. That means the result could be the opposite of the true result 96% of the time.

Reverse Causation

In the case of sodium and cardiovascular disease, reverse causation is likely in secondary reviews of data. Participants in the original studies often have cardiovascular disease. They are often on a low sodium diet, either self-determined or determined by their doctor. The participants also are often on diuretics or other medications that change the amount of sodium in their urine, leading to imprecise estimates of sodium intake (discussed below). So rather than low sodium intake leading to cardiovascular disease, cardiovascular disease leads to low sodium intake, i.e. reverse causation.

Imprecise Estimates

Limited urinary sodium collections are used in many studies. Previous studies had shown some correlation of short urinary collections of sodium with 24 hour collections. Many of the studies included in this particular meta-analysis had only spot collection or short period collections. Of the 25 studies that were included in the meta-analysis only 2 had multiple 24 hour urine collections.

But it is now known that limited urinary sodium collections are an imprecise estimate of sodium intake. Only recently sodium excretion has been discovered to have a cyclical variation lasting longer than a day. A recent study (3) showed the imprecision of spot, and even single 24 hour, urinary sodium collections. The findings come out of a study done for the Mars flight program.

In a highly controlled environment, the researchers showed that there will be a high degree of inaccuracy in 24 hour urinary sodium collections as an estimate of sodium consumption. In a single 24 hour urine collection, only one half of the collections will be accurate within 3 grams of the amount of sodium taken in during the prior 24 hours. If 3 sequential samples are examined, the collection will achieve 75% accuracy. And if 7 samples are used, it will have a 92% accuracy.

The Problems With This Study

In addition to the problems of all secondary studies that use re-purposed data, there also were problems specific to this meta-analysis. The meta-analysis authors chose cutpoints for their groups that were entirely different than any other studies. The cutpoints were markedly different from those chosen by the Institute of Medicine (IOM) and American Heart Association (AHA) for their recommendations. The authors chose 2645 mg/day and 4945 mg/day instead of the 1500 mg/day and 2300 mg/day used by the IOM. The difference makes comparison of the meta-analysis data with other studies very difficult. It also raises the question of why the researchers chose different cutpoints.

The authors of the meta-analysis also did multiple testing for comparisons of their outcomes across 4 outcomes and 5 levels of sodium intake. This multiple testing increased the probability of their results only being due to chance.

And finally, it could not be determined how consistent their findings were because of inadequate data in the article and in the supplementary material. Two of the cohorts that they used were the NHANES I and NHANES III. When alternative analyses of these cohorts were done, entirely different results were obtained showing no increased risk from the lower salt intake. Using the alternative analyses resulted in the hazard ratio from lower salt intake being 0.99. This ratio meant there was no increase in risk of cardiovascular death.

Studies With Higher Quality Data

The commentary then cited 2 recent cohort studies, not included in the meta-analysis, that were of higher quality than those included in the meta-analysis. Both of these studies showed an association of higher sodium intake and CVD. One of these studies was the TOHP study that showed a linear trend for the relationship between sodium and cardiovascular disease even at the lower end of sodium intake. This study used only healthy participants and collected multiple 24 hour collections. This is far more relevant to answering a question about prevention than one including patients who already have the disease.

Another high quality study was a randomized controlled study designed specifically to examine the relationship of sodium and potassium to cardiovascular disease. It was the Taiwanese study that we discussed in our post here. In this particular study the cardiovascular mortality hazard ratio was reduced to 0.59 when the sodium was reduced. However in this Taiwanese study some of the sodium was replaced with potassium so that an even higher ratio of potassium to sodium was obtained in the diet than would have been obtained simply by reducing sodium. This study was not included in the meta-analysis.

As the commentary relates, the highest quality studies show that less sodium intake results in less cardiovascular disease in healthy people, even at the lower levels recommended by the IOM and AHA. Secondary analysis of studies designed for another purpose have not given results of adequate quality. But such secondary studies will continue to provide enough confusion that little will be done to change national food practices. It will be up to individuals to reduce sodium intake and increase potassium intake on their own.

If you want to reduce your chance of cardiovascular disease, hypertension and strokes to the lowest possible chance, do not wait for the nation to change the food supply. Do it on your own. Reduce your sodium consumption to less than 1500 mg per day and increase your potassium consumption to more than 4700 mg per day. Go on the high potassium foods diet.
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1. Compared with usual sodium intake, low- and excessive-sodium diets are associated with increased mortality: a meta-analysis. Graudal N, Jürgens G, Baslund B, Alderman MH. Am J Hypertens. 2014 Sep;27(9):1129-37. doi: 10.1093/ajh/hpu028. Epub 2014 Mar 20.

2. Sodium and cardiovascular disease: what the data show. Whelton PK, Appel LJ. Am J Hypertens. 2014 Sep;27(9):1143-5. doi: 10.1093/ajh/hpu138.

3. Agreement Between 24-Hour Salt Ingestion and Sodium Excretion in a Controlled Environment. Lerchl K, Rakova N, Dahlmann A, Rauh M, Goller U, Basner M, Dinges DF, Beck L, Agureev A, Larina I, Baranov V, Morukov B, Eckardt KU, Vassilieva G, Wabel P, Vienken J, Kirsch K, Johannes B, Krannich A, Luft FC, Titze J. Hypertension. 2015 Oct;66(4):850-7. doi: 10.1161/HYPERTENSIONAHA.115.05851. Epub 2015 Aug 10.

High potassium foods are foods that are low in sodium and high in potassium and that produce an alkaline urine. The low sodium aspect of the diet has been challenged in the past and continues to be challenged today. Because the argument is still heard that a low salt diet may be dangerous to healthy people, it is important to review how this argument started, why it was no good in the first place, and how much evidence there is against it.

Beginnings – Low Sodium Diet Danger

Articles were published in the late 1990s, and there have been more since, that reported increased deaths with low sodium consumption. Two of the original articles are representative (1, 2). They reported an inverse relation of sodium and heart attacks or cardiovascular disease mortality. This inverse relationship became modified subsequently. Subsequent publications questioning the safety of a low sodium diet usually reported a J-shaped or a U-shaped curve to the graph of the relationship of sodium to mortality. These articles claimed that there was a higher mortality at a low sodium intake that dipped down to a low point at about what the average intake is in Westernized society. It then moved up to a higher mortality at higher levels of sodium, forming a J-shape or U-shape to the graph.

There have been multiple articles pointing out the flaws in the publications that make these claims. In 2002, publication of a series of commentaries between the main proponents and the main antagonists presented the main arguments for both sides of the argument. These commentaries provide a very nice summary of the main arguments still being used today for and against the recommended 2300 mg and 1500 mg levels of sodium.

The First Commentary

The original argument against a low sodium diet can be understood from two representative publications (1, 2) in the 1990s. There were a few other similar articles by the same authors, and other authors, during that period, and there have been multiple articles with similar conclusions since then. In the first of these commentaries (3) the main author of those first two articles, Dr Alderman, argues in favor of increased mortality from the low sodium intakes recommended by several medical organizations. He discussed two unique populations that he claimed supported this view.

The first population Dr Alderman discussed was the Kuna Indians in Panama. They were claimed to have the same sodium intake as the urban Kuna, but not have the increase in blood pressure of the urban Kuna. The findings of this publication have had some problems with acceptance. The authors stated that their study was a feasibility trial, but nonetheless reported their findings. The potassium and sodium content of the food items in the Kuna diet (reported in a separate report) did not correspond to the results of the research. And the methods used to collect estimates of food intake were flawed.

The Kuna were reported to consume considerable amounts of cocoa that had a high potassium content. Much of the remainder of their food had a high potassium to sodium ratio. This potassium would negate much of the cardiovascular effects from the increased sodium intake. Yet the estimated sodium and potassium intake did not correspond with this food composition.

The methods used to obtain these estimates of sodium and potassium have problems. There were two statements in the Kuna articles about how the researchers estimated the amount of sodium ingested. One method mentioned was estimation of sodium from a single 24 hour urine collection. However, the author stated that approximately 1/2 the collections were incomplete. In the second method of estimation, the Kuna participants were asked to estimate the number of teaspoons of salt they ate, as well as give estimates for other food items. The methods used to collect estimates of food intake have been objected to by an anthropologist, Jeffrey Barnes, as being inaccurate because of known cultural factors.

The author also discussed a 30 year observational study of some nuns who had low blood pressure. 144 nuns living in extreme seclusion had sodium intakes similar to women in a nearby community. They did not have the age-related blood pressure increase of the community women. The authors of the nun study felt the difference in blood pressure was due to psychosocial factors. There have been no confirmatory studies done.

This first commentary discussed the Intersalt study, which is a major study showing the importance of a low sodium diet. The commentary author misstated the findings of this extensive study, saying simply “no association between sodium intake and blood pressure” was found in the 48 cosmopolitan centers included in the study. Later in this post, the commentary by two of the authors of the Intersalt study refute this claim.

In his discussion of animal studies he quoted only a small amount of animal work in which he obfuscated the findings. The enormous body of animal work showing the response to high salt and low-salt intake he ignored and did not discuss at all. He also discussed the effect of sodium on renin, and misunderstood the effect of sodium on blood vessels. He did not discuss any other basic science.

There is an extensive body of basic science even prior to 2002 and this has only grown considerably since then. The basic science since 2002 has clarified even more how sodium and potassium interact. This science shows how sodium is easily conserved by the body and potassium is easily excreted. The post here discussed this beautiful recent work showing how the kidney does this.

The Second Commentary

There were 4 commentaries that followed Dr Alderman’s. The first was by Dr Elliott and Dr Stamler who were two of the authors of the Intersalt study. This response, and the response of Dr MacGregor and Dr de Wardener were far more extensive than those of the proponents of the danger of a low sodium diet. The final response was briefer, but included a few publications not previously mentioned. It supported the safety of a low sodium diet. The response after the response of Dr Elliott and Dr Stamler was in support of the potential danger of a low sodium diet. It was quite brief, but discussed that other dietary factors may be responsible for any favorable effects.

The response (4) by Dr Elliott and Dr Stamler pointed out the major problems with the studies that challenge the effectiveness and safety of a low sodium diet. They also pointed out the major categories of studies that support a low sodium diet. The supporting studies that they mentioned include human experimental, epidemiological, anthropological, and human observational studies. The human observational studies alone numbered over 50.

They pointed out the results of the DASH-sodium study. This study supplied all the food to the participants, giving high accuracy to the sodium intake estimates. In this study, the participants were divided into 3 low sodium groups. Each of the 3 groups showed lower blood pressure as sodium was reduced.

The Intersalt study showed higher blood pressure was associated with higher sodium intake in 48 modern populations, as well as in 4 indigenous populations. Dr Alderman’s assertion that there was no direct correlation of blood pressure with sodium was completely refuted by this study and in this commentary.

The Third Commentary

This commentary was followed by another commentary (5) by two other proponents questioning the effectiveness of the low sodium diet. These authors basically confused the issue by bringing in other aspects of diet as a possible reason for the effect of sodium. Because other aspects of diet were also changed in the DASH-sodium trial, the authors propose that the other aspects of diet may be responsible for the blood pressure effect. These other aspects may have contributed to lower blood pressure, but have less support in the literature than the support for the effect of sodium.

The Fourth Commentary

The penultimate commentary (6) is by Dr MacGregor and Dr de Wardener of the United Kingdom, who discussed even more studies showing the importance of a low sodium intake to reduce blood pressure. They discussed some of the articles that Dr Elliott and Dr Stamler discussed. But they included more clinical studies, and they also included more basic science articles. The authors discussed the lack of vascular disease and hypertension in the indigenous Yanomami, discussed in this post. They pointed out that the Yanomami develop vascular disease, diabetes and become overweight when they migrate to towns and adopt a western lifestyle. They do not differ from others living indigenous lifestyles who migrate to Western lifestyles, as discussed here.

These two authors discussed the Portuguese interventional study in which one village was given processed foods with less salt, and a second village that was kept on their normal diet. The first village’s sodium intake was reduced by 50%, leading to lower blood pressure in that village. The second village had no change in blood pressure.

The basic science studies the authors discussed included some discussed here and here, showing effects of sodium on scarring of the heart and stiffening of the blood vessels. Additionally, they pointed out the possible conflict of interest of the author of the first commentary. That author has acted as a member of the Medical Advisory Board for the Salt Institute, which represents the salt manufacturers.

The Fifth Commentary

The final commentary (7) included many of the previously discussed reports, and added discussion of a few not previously discussed, such as 3 randomized controlled studies. These commentators also supported the safety of a low sodium diet as preventive for cardiovascular disease.

The Response

At the very end, there is a response by the original commentator, Dr Alderman, to the low sodium proponents. He basically argues that the “diets of millions of healthy people or hypertensive patients should be based on empirical evidence” that the recommended change would be beneficial. He ignores the finding that the weight of evidence in favor of the low sodium diet overwhelms the contrary evidence. And he ignores the evidence that basic science supports the high potassium, low sodium diet. The basic science also explains the contrary empirical evidence that he so favors. This basic science is consistent with damage from a prior high sodium, low potassium diet causing an increased risk of cardiovascular death, even when sodium is later restricted.

Potassium Is Not Considered

Neither the authors who favored the effect of sodium on blood pressure, nor the authors who favored the lack of effect, and potential danger, of low sodium intake discuss the importance of potassium. Nor do they discuss the potassium sodium ratio. However this lack of consideration of potassium has been common throughout the medical literature, and does not in any way negate the importance of lowering sodium.

Sodium and potassium work in concert. More and more studies are showing the importance of the potassium sodium ratio as more and more physicians become aware of the basic science behind the ratio. The importance of potassium in no way negates the importance of a low sodium diet. It actually bolsters the importance of a low sodium diet, since less sodium improves the potassium sodium ratio if the amount of potassium is unchanged in the diet.

Although this series of point and counterpoint is from 2002, the same arguments are being heard today. Since that time there has continued to be an ever mounting, massive amount of basic science that demonstrates the importance of the potassium sodium ratio. More evidence of its effect on the cell membrane potential (electric field), and how the cell membrane potential affects kidney cells, adrenal gland cells, heart cells, and blood vessel cells appears every week.

Low Sodium Diet And Reverse Causation

The studies that started this debate in the medical community basically showed reverse causation. The people in these studies on a low sodium diet were already very ill with heart damage. They would be expected to have a higher rate of death from heart disease than those on a higher salt diet who were not so sick. Studies that have not included these highly ill patients have shown that sodium consumption all the way down to 1500 mg per day lowers, rather than increases, the risk of heart disease. The post last week discussed a very careful study showing this very clearly.

There are few areas in preventive medicine that have so much strong evidence in their favor. The evidence in favor of a diet with a high potassium sodium ratio for healthy people is overwhelming. Its value for the prevention of strokes, cardiovascular disease, and kidney disease is solid. And the evidence for its value in the prevention of even some other diseases is growing.
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1. Low urinary sodium is associated with greater risk of myocardial infarction among treated hypertensive men. Alderman MH, Madhavan S, Cohen H, Sealey JE, Laragh JH. Hypertension. 1995 Jun;25(6):1144-52.

2. Dietary sodium intake and mortality: the National Health and Nutrition Examination Survey (NHANES I). Alderman MH, Cohen H, Madhavan S. Lancet. 1998 Mar 14;351(9105):781-5.

3. Salt, blood pressure and health: a cautionary tale. Alderman MH. Int J Epidemiol. 2002 Apr;31(2):311-5.

4. Evidence on salt and blood pressure is consistent and persuasive. Elliott P, Stamler J. Int J Epidemiol. 2002 Apr;31(2):316-9; discussion 331-2.

5. Salt, blood pressure and public policy. Freeman DA, Petitti DB. Int J Epidemiol. 2002 Apr;31(2):319-20; discussion 331-2.

6. Salt, blood pressure and health. MacGregor G, de Wardener HE. Int J Epidemiol. 2002 Apr;31(2):320-7; discussion 331-2.

7. Salt intake, hypertension and risk of cardiovascular disease: an important public health challenge. He J, Whelton PK. Int J Epidemiol. 2002 Apr;31(2):327-31; discussion 331-2.

The high potassium foods diet has been shown to reduce blood pressure, strokes, and cardiovascular disease. These foods have a high ratio of potassium to sodium, and they produce an alkaline urine. This diet can be obtained by increasing the potassium and/or decreasing the sodium in the usual diet. Emphasis for many years has been on reducing sodium, because the greatest amount of research has been done on sodium. If potassium intake remains the same, less sodium should result in a higher potassium sodium ratio, and should result in less cardiovascular disease.

Disputing Sodium Guidelines

Several medical organizations have produced guidelines that recommend lowering sodium intake to prevent cardiovascular disease. Although there are many medical studies to support these guidelines of getting less than 2300 mg of sodium, preferably less than 1500 mg of sodium, there are publications that dispute the guidelines. These publications claim that the lower levels recommended are unsafe.

Such publications claiming that less sodium is not safe generally say there is a J-shaped or U-shaped curve to mortality and sodium consumption. They claim there is increased risk of cardiovascular disease and death at the more restricted levels of less sodium consumption. They often make this claim broadly, not saying that it may be true only in limited circumstances. Such claims are highly misleading, making healthy people afraid to lower their sodium intake to the recommended levels.

However the problems with such claims are many. The broad health claim that less sodium is dangerous for a healthy person is totally unfounded. And it may be dubious for most higher-risk people unless they have very specific circumstances. The publications that these claims are based on are filled with flaws.

The Main Flaw

Of all the flaws with these publications, there is one major, universal flaw that stands out. All of the studies were based on secondary analyses of studies designed for a purpose other than determining the relationship of sodium intake to subsequent cardiovascular disease.

For example, an often cited study (1) used patients with established cardiovascular disease who were already on the drugs telmisartan and ramipril to determine mortality of a low sodium diet. They extracted data from 2 previous studies. The first study (ONTARGET) that they used was designed to compare the effects of the daily use of ramipril 10 mg to the daily use of telmisartan 80 mg. The second study (TRANSCEND) was designed to compare daily use of telmisartan 80 mg to placebo in patients intolerant to ACE inhibitors.

The problem with using studies designed for another purpose is that important data needed will not be present. Telmisartan, for example, produces increased sodium excretion in the urine (2). Although more excretion occurs during the first few days, it continues long term. The urinary sodium will certainly be affected by the medication. With spot urine collections, the sodium excreted will vary according to when the urine is collected. It varies throughout the day and from day to day normally in people not on medication, and varies according to the length of time since the medication was taken. Almost all of these secondary studies include primary studies that used spot urine collections.

Using data from these studies, the authors concluded in their abstract that the “association between estimated sodium excretion and CV events was J-shaped.” Thus they indicate that the association applies to everyone. In the body of the paper they add a little more specificity, saying that this association is true for “those at increased CV risk.” But even this may not be true, since it really only applies to those on these medications. And only if the spot urines accurately reflect sodium balance, which they probably do not. The inaccuracy of spot urines for sodium and potassium will be discussed in a future post.

TOHP Study

The study to be discussed today does not have such flaws. It was designed specifically to determine the relationship of cardiovascular disease to sodium and potassium as part of a nutritional supplement intervention and lifestyle intervention. It is a follow-up report (3) on the Trials of Hypertension Prevention (TOHP) study.

The TOHP study was done in two phases, TOHP I and TOHP II. The TOHP I study restricted the participants to those who were pre-hypertensive. TOHP II restricted participants to those who were pre-hypertensive and overweight. Severe hypertensives on diuretics and anti-hypertensive drugs, which distort urinary sodium and potassium, were excluded from the original studies. Also excluded from the present follow-up study were any participants who had been in the active sodium reduction intervention in the original studies.

This report cites the 10 year and 15 year follow-up of the TOHP study. They combined the data from the two phases. The results showed that the participants had an average sodium excretion of 3630 mg of sodium in 24 hours. Only 10% of the participants in this study had less than 2300 mg excreted in 24 hours. And 1.4% of participants excreted less than 1500 mg a day. The researchers sent questionnaires to the participants. Medical records of any who indicated events related to cardiovascular disease or who died were examined.

Less Sodium Means Less Risk

The study found that compared to the risk of those with a consumption of 3600-4800 milligrams of sodium a day those who consumed less sodium than 2300 mg had a 32% lower cardiovascular risk. The researchers plotted the sodium consumed against the hazard of having a cardiovascular event and found a continuous reduction in risk. The graph did not show any J or U-shaped curve but rather a continuous reduction in risk as sodium excreted dropped from 10,000 mg/day to less than 1000 mg/day.

One of the problems with the studies finding increased risk from low sodium intake is that they only did spot urines. Because there is a great deal of variability in sodium intake on any particular day there can be a great deal of inaccuracy with these. This problem was eliminated in the TOHP study. During the active study period of the TOHP study, the researchers collected 24 hour urine specimens. They collected urine samples 3 to 7 times over the study period. Additionally the first study lasted 18 months and the second study 2 to 3 years. This should give far more accurate measurements of average daily sodium and potassium intake than a single spot urine collection.

So for those who are healthy or have early disease, such as prehypertension or newly diagnosed hypertension, the high potassium foods diet (which has a low sodium as well as a high potassium intake) should prevent hypertension and cardiovascular disease. The diet has less sodium and more potassium than the average American diet. For some with early disease, it may reverse the disease. But for those with advanced cardiovascular or kidney disease, careful management of diet should be done by their health care provider.
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1. Urinary sodium and potassium excretion and risk of cardiovascular events. O’Donnell MJ, Yusuf S, Mente A, Gao P, Mann JF, Teo K, McQueen M, Sleight P, Sharma AM, Dans A, Probstfield J, Schmieder RE. JAMA. 2011 Nov 23;306(20):2229-38. doi: 10.1001/jama.2011.1729.

2. I026: Long-term effect of telmisartan on sodium excretion in hypertensive patients. Burgess ED, Buckley S. Am J Hypertens (2000) 13 (S2): 183A-184A. doi: 10.1016/S0895-7061(00)01172-9.

3. Lower levels of sodium intake and reduced cardiovascular risk. Cook NR, Appel LJ, Whelton PK. Circulation. 2014 Mar 4;129(9):981-9. doi: 10.1161/CIRCULATIONAHA.113.006032. Epub 2014 Jan 10.

Here we go again. Claims about the low sodium diet being deadly. These types of papers resurface every few years and elicit multiple responses pointing out their flaws. Occasionally the response takes the form of a review paper discussing high quality studies. Such papers usually limit the studies they report on to sodium studies. The publication (1) to be reviewed today is one of the few that reviews both sodium and potassium. The authors reviewed the recent medical literature and found 52 publications that studied sodium, potassium, or both and the relationship to cardiovascular disease. They limited their reviews to randomized controlled trials (RCT). RCTs are considered the gold standard for clinical intervention studies.

Flawed Studies

This paper was done in response to a recent high profile paper (2) that was published in 2011 and rekindled a recurring debate about the safety of a low sodium diet. As is usual with these papers, the evidence was lacking in strength. The paper was observational and had the usual problems with design and methods. A major issue in this particular paper was the under-collection of 24 hour urine samples in the group purported to have the lowest sodium intake.

This debate about the safety of a low sodium diet started in the 1990s when some studies reported that consuming sodium at the lowest level recommended by the Institute of Medicine led to an increase in cardiovascular mortality. The authors of those studies reported that modest reductions in sodium could have a favorable effect, but that more intense reductions lead to more deaths. This is the often discussed U-curve or J-curve. These earlier studies have been discussed and reviewed extensively in the medical literature. There are multiple serious flaws with these studies.

One of the easiest flaws to understand occurs repeatedly in many of these papers. It is reverse causation. This flaw is present when the group of individuals with the lowest sodium intake has a higher percentage of people with serious health conditions, especially heart and kidney conditions. This means the low sodium group has more people who were far more likely to die than any of the other groups. They are on a low salt diet to try to improve their condition. In other words, their deadly condition is the cause of being on a low salt diet, not that the low salt diet is the cause of their deadly condition – i.e., reverse causation.

Other problems that commonly occur include the inaccuracy of spot urinary sodium representing sodium intake in those on medications for hypertension, under-collection of 24 hour urine collections, use of inappropriate statistical methods, and inclusion of inappropriate studies that were originally designed for a different purpose if the study is a meta-analysis.

To avoid such problems, the authors of the present publication excluded papers on several grounds. The paper was excluded if it did not include relevant data, such as systolic and diastolic blood pressure, or did not include indicators of kidney and vascular damage. A major reason to exclude a paper was if it was examining patients with heart failure.

Findings

The authors found 52 publications of randomized controlled trials (RCT) that met their criteria of a dietary sodium and/or potassium intervention, and a method to assess the actual dietary sodium and/or potassium intake. In 28 of the studies only sodium was modified in the diet. These studies showed that a decrease in sodium had a favorable effect on cardiovascular disease. The authors found 12 studies that modified potassium only. They found 12 studies that modified both sodium and potassium. Furthermore, in this last group they found 2 studies in which a strong relationship was shown with a dose response curve.

When they looked at grading the quality of the studies, the authors found many of the studies were of high quality, which they graded A. This grade meant that further research would be unlikely to change the confidence in the estimate of the effect found by the study.

Based on the grades of the studies, they used two levels to determine how strong a recommendation was. Level 1 meant that “most people in your situation would want the recommended course of action and only a small proportion would not.” Level 2 meant that “the majority of people in your situation would want the recommended course of action, but many would not.”

Recommendations For Healthy And Unhealthy

The authors found that the quality of the sodium studies led to a Level 1 recommendation to reduce salt to prevent cardiovascular disease. Even the lowest level of sodium intake was safe and helpful. They found that the potassium studies led to a Level 1 recommendation to increase potassium intake to prevent cardiovascular disease. Thus the recommendations of the IOM, AHA, and USDA concerning sodium and potassium in the diet were supported by the highest quality research. Levels of sodium below 1500 mg per day were safe and reduced cardiovascular disease. Levels of potassium above 4700 mg per day were safe and reduced cardiovascular disease.

The authors then concluded with some recommendations for doctors treating patients. They felt that there were strong recommendations to reduce sodium and increase potassium in the diet. There was strong evidence that these changes in diet would reduce blood pressure and reduce all the sequelae of hypertension and cardiovascular disease.

However, if someone already had damage to their heart or kidney, they would need extra special care. Those with severe heart failure requiring high dose medications would not benefit from salt restriction. Those with salt wasting tubulopathies (a kidney disease) would need close supervision of their salt intake. Patients with advanced kidney disease would need careful monitoring to prevent development of too much potassium in the blood. Patients with multiple advanced diseases complicating their medical care would need individualized dietary management.

A high potassium foods diet would not be likely to help these individuals with advanced organ damage. A high potassium foods diet is a preventive diet that will prevent cardiovascular disease. But it is not a therapeutic diet for those with advanced organ damage.

For links to tables of high potassium foods, click the tab at the top of the page, labelled “Links To Food Potassium Tables.”
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1. Role of dietary salt and potassium intake in cardiovascular health and disease: a review of the evidence. Aaron KJ, Sanders PW. Mayo Clin Proc. 2013 Sep;88(9):987-95. doi: 10.1016/j.mayocp.2013.06.005.

2. Fatal and nonfatal outcomes, incidence of hypertension, and blood pressure changes in relation to urinary sodium excretion. Stolarz-Skrzypek K, Kuznetsova T, Thijs L, Tikhonoff V, Seidlerová J, Richart T, Jin Y, Olszanecka A, Malyutina S, Casiglia E, Filipovský J, Kawecka-Jaszcz K, Nikitin Y, Staessen JA; European Project on Genes in Hypertension (EPOGH) Investigators. JAMA. 2011 May 4;305(17):1777-85. doi: 10.1001/jama.2011.574.

High potassium foods are foods that are high in potassium and low in sodium, giving a high ratio of potassium to sodium. They are important for the prevention of hypertension. Hypertension is becoming more and more common worldwide, and is the greatest risk factor for stroke, heart attack, and congestive heart failure, as well as for overall death. The possible causes of hypertension are an area of extensive work being reported in the medical literature. Starting approximately 60 years ago sodium became the main area of interest in the study of hypertension. The article (1) to be discussed today goes through a brief history of how salt sensitivity in hypertension came to be studied. It then goes into the modern knowledge of salt sensitivity, emphasizing its molecular mechanisms and epigenetics, and does some speculation on the future.

History

In the 1960s Dahl bred rats that within 3 generations developed hypertension with increased salt intake. This allowed him to study various aspects of how salt influenced blood pressure.

At approximately the same time, Dr. Guyton showed that dietary sodium and the ability of the kidney to get rid of sodium controlled long-term blood pressure. He used an engineering model to show these relationships mathematically. Since his work, this model has been well tested in animals and in patients receiving kidney transplants.

Dr. Guyton showed that those who are sensitive to salt differed from those who were resistant to salt. This is something he labeled the renal function curve. He showed that those who are resistant to salt can excrete more sodium through the kidneys as blood pressure rose. Those who were sensitive to salt (sodium) had a larger rise in their blood pressure for the same amount of sodium excreted.

Dahl’s studies showed that there is a genetic role in the sensitivity of blood pressure to salt. Since that time, there have been multiple animal models developed to study the genetics of salt sensitivity. These animals all have genetic makeups that differ from one group of animals to another. These models have shown a great deal about the genetics of hypertension, and about the interaction of genetics with environmental factors, as well as about the interaction of genes with other genes in hypertension.

GWAS

Genetic Wide Association Studies (GWAS) have been discussed previously here and here. They have shown some important single gene changes associated with hypertension. But these gene changes only represent a small percentage of the people who have hypertension. GWA Studies have discovered less than 1% of the estimated genes involved in hypertension. This is because the most common genetic changes associated with hypertension are polygenic (more than one gene) changes. In addition to there being multiple genes influencing the sensitivity of blood pressure to sodium, researchers have found that there are interactions between these genes with each other, and between these genes and the environment.

Salt Sensitivity Epigenetics

For a cell, the environment is the fluid that the cell sits in and the cells that are adjacent to it. This fluid contains sodium and potassium. A major factor in a cell’s environment is the concentration of sodium and potassium in this fluid. This factor influences the cell membrane potential. Changes in the cell membrane potential set off multiple cascades of chemical reactions within the cell. Some of these reactions will affect the genes in the cell through epigenetic factors.

For scientists studying epigenetic factors, the exact definition of epigenetics is still evolving. There is debate about whether the epigenetic changes can be inherited. But in this article the authors only consider whether the gene confers “susceptibility” to blood pressure elevation from an epigenetic factor. The authors also use the generally accepted part of the definition of epigenetic factors that they are factors that suppress or activate genes without changing the DNA sequence of the actual gene itself.

These factors are how the environment interacts with the gene, especially how the environment immediately surrounding the gene interacts with it. The epigenetic factors may affect genes by turning them on or off. They affect how the cells read the genes. Sometimes they affect the genes by speeding up or slowing down their expression. Or they may involve other genes that interact with each other. Two gene-environment interactions often cited are methylation of DNA and modification of histones. Histones are proteins that DNA wraps around. If the shape of the histones changes, the genes available for reading will change. This can change how a gene is expressed without changing the gene itself. When this occurs in kidney cells or adrenal cells, it can have an effect on blood pressure.

The authors then go into many potential gene locations and possible influences on these genes that potentially affect sodium sensitivity. Some readers may not be interested in the detailed science in this portion of the publication. The authors discuss several methods of looking at specific suspected genetic determinants of blood pressure. This portion of the article would be of interest to doctors and other researchers who can devise experiments about salt sensitivity based upon the authors’ speculations. Nonetheless, this part of the publication shows the importance that dietary sodium has on the level of blood pressure, and on the sequelae of hypertension.

Based on their own work, the authors also present some exciting ways to possibly prevent some of the sequelae of hypertension, such as scarring of the heart or scarring of the kidney. The cellular mechanism of the heart scarring was discussed in this post. The authors discuss their experiments that showed prevention and even some reversal of hypertensive heart scarring. They did this by immunizing animals against a particular molecule that is produced by the heart when there is excessive sodium in the diet. Some experiments they discuss also indicate that this immunization may protect against the scarring in the kidney that occurs from excessive sodium in the diet.

Sodium Is Half The Equation

But excessive sodium in the diet is only one half of the equation. Potassium is the other half. It is the interaction of these two ions that is crucial to blood pressure.

Their interaction is determined by their ratio. When sodium is affected, there is an effect on potassium. If a potassium ion leaves from inside the cell, a sodium ion must enter to take its place. If there is too much sodium outside the cell from too much dietary sodium, some sodium will push into the cell. For every extra sodium inside the cell, a potassium is kicked out.

Either way, excessive sodium and/or inadequate potassium reduces the cell membrane potential and leads to many cellular processes that would not occur with a normal cell membrane potential. On this website multiple posts have discussed this interaction, and multiple posts in the future will also discuss this interaction. All of this interaction is controlled by the potassium and sodium content of the food that you eat. If the foods are high in potassium and low in sodium, the ratio will be optimal.
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1. Molecular mechanisms of experimental salt-sensitive hypertension. Joe B, Shapiro JI. J Am Heart Assoc. 2012 Jun;1(3):e002121. doi: 10.1161/JAHA.112.002121. Epub 2012 Jun 22.