Under Appreciated Issues in the Treatment of Chronic Illness – Low Grade, Chronic Acidosis Combined with Potassium Deficiency – Part IV – Why We Need to Pay More Attention to Diet Induced Acidosis


As those of you who have been following this series since I began it in May of 2018, there was a somewhat lengthy period of time between part III and part IV, which I am writing now for the July 2019 Moss Nutrition Report.  Why did I take a break from this series for such a long time?  One reason is that I kept on finding updated, highly clinically relevant research that was suggesting that dietary protein and muscle physiology is just as important and just as underappreciated as metabolic acidosis and potassium.  Why am I going back to this series after all this time?  The main reason, other than the high quality papers I am about to review, is that, since I started this series back in May of last year, from my vantage point not much has changed in the clinical nutrition and function medicine community in terms of emphasis on metabolic acidosis and potassium biochemistry and physiology.  Even though reports from many of you verify what has been reported in the medical literature that optimization of acid/alkaline balance in general and potassium metabolism specifically has a tremendous positive impact clinically, I cannot recall within the last year even one major functional medicine symposium that placed significant emphasis on this issue.  As I pointed out in part I of this series written in May 2018, I was mystified by this lack of attention by the nutritional and functional medicine community.  Now, over one year later, I remain just as mystified.

What is the best solution to this problem?  For me, it is to do my best to continue to bring attention to the vast, virtually ignored body of research on acid/alkaline balance and potassium metabolism to all those who are open to reading this information and bringing it into their practices to further improve the health of the chronically ailing individuals who have followed the usual functional medicine diagnostics and protocols and are still experiencing suboptimal quality of life.

As you may also recall, much of the emphasis in this series through part III has been on the impact of suboptimal potassium intake and metabolism on chronic illness.  Therefore, in part IV of this series I would like place primary focus on papers that specifically address this issue of diet-induced metabolic acidosis and why it is so important clinically in terms of resolving chief complaints in chronically ailing individuals.


The above question was answered in fine fashion by the paper “Diet-induced acidosis: is it real and clinically relevant by Pizzorno et al (1).  The first quote I would like to feature from this paper provides an overview of how the body tightly controls pH:

“The human body tends to maintain a tightly controlled pH of about 7.4 in the extracellular fluid by respiratory excretion of carbon dioxide and renal excretion of non-carbonic (non-volatile) acid or base.”

How can diet contribute to an acidotic state?  The authors suggest:

“While acute acid loading may only temporarily disrupt acid-base equilibrium, a chronic perturbation occurs when metabolism of the diet repeatedly releases non-carbonic acids into the systemic circulation in amounts that exceed the amount of base released concomitantly.”

How does the body maintain pH equilibrium in the face of increased acidic foods?  Pizzorno et al (1) point out:

“To maintain equilibrium when there is a net retention of acid (H+), at least three compensatory physiological responses are activated: buffering, increased ventilation, and increased renal reabsorption and generation of HCO3.”

What are the main sources in the body of buffering factors?  As you might guess from past newsletters and general popular knowledge about bone metabolism, they are bone and muscle:

“The major reservoir of base is the skeleton (in the form of alkaline salts of Ca) which provides the buffer needed to maintain blood pH and plasma bicarbonate concentrations.  To some degree, skeletal muscle also acts as a buffer.”

Concerning the use of bone as a buffering factor, it has conventionally been thought of as a passive process.  However, the reality is that it is a highly active process mediated by osteoclasts:

“…the loss of bone mass due to acidosis has generally been considered a passive process, a physio-chemical dissolution of the matrix.  However, bone dissolution is more than just a passive process, but rather is one of active resorption by osteoclasts, with extracellular H+ being a key inducer of osteoclastic activity.  Indeed, extracellular H+ has been suggested to be the ‘long-sought osteoclast activation factor…”

Thus, acidic H+ ions induced by an acidic diet can actually induce osteoclastic activity.  In turn, an acid diet can be a powerful factor in stimulating bone loss.  Furthermore, as noted in the following quote, neutralizing an acid diet with alkaline factors can slow this osteoclastic activity:

In vivo studies have generally supported the in vitro findings that acid-promoting diets are associated with both increased Ca and increased bone matrix protein excretion (used as a marker for estimating bone loss), and that neutralizing the acid intake with diet or bicarbonate supplements decreases urine Ca and bone matrix protein excretion.  In a trial of 170 postmenopausal women, for example, potassium bicarbonate supplementation reduced daily urinary Ca excretion, and one could predict which women would benefit most – those with the greatest urinary Ca loss.”

In the next quote Pizzorno et al (1) discuss how the process discussed above can contribute to the formation of kidney stones:

“Additionally, the same mechanism may be involved in Ca nephrolithiasis.  A common risk factor for Ca stone formation appears to be hypocitraturia, which has been associated with a low urinary K level and a more acidic urinary pH, both of which can be predicted by dietary intake.  However, it appears that dietary acid load is a better predictor of urinary citrate than the intake of most individual nutrients, including dietary K.” 

With the above in mind, even though traditional nutritional thinking tends to focus on intake of individual nutrients when considering conditions such as kidney stones, a better indicator of risk of stone formation is the overall acid/alkaline balance of the diet.


In the next section of their paper Pizzorno et al (1) provide more detail on the general, more well-known causes of metabolic acidosis:

“The causes of metabolic acidosis include increased consumption or generation of organic acids, as well as either insufficient production of bicarbonate, or renal and/or gastrointestinal loss of bicarbonate, such as that seen with renal disease, diarrhea, pancreatic drainage, and biliary fistula.”

However, the low-grade acidosis induced by diet is somewhat different:

“In comparison, diet-induced ‘low-grade’ metabolic acidosis has only very small decreases in blood pH and plasma bicarbonate within the range considered to be normal.”

As you might guess, because diet-induced, low-grade metabolic acidosis does not produce rapid and profound changes in the usual laboratory indicators of acidosis, it is conventionally regarded as clinically insignificant.  However, as noted in the quote below, even though diet-induced, low-grade metabolic acidosis is not clinically significant based on traditional short term, quantitative measures, it is clinically significant due to the fact that its duration can be long-term:

“But if the duration of the acidosis is prolonged or chronically present, even a low degree of acidosis becomes significant.”

Beyond duration, why is it clinically significant?  As noted below, two reasons are increasing age that often entails loss of renal function plus the high salt content of many typical acidotic diets:

“This less severe but more chronic ‘low-grade’ acidosis is thought to be brought about primarily by two factors: advancing age with a consequent decline in renal function, and diet, which may promote acidosis by both its net acid load, as well as its sodium chloride content.”

The next quote provides further discussion on the impact of age-related loss of renal function:

“With age, the severity of diet-dependent acidosis increases independently of the diet, most likely due to a decline in kidney functional capacity with age.  Renal insufficiency contributes to a metabolic acidosis by reducing conservation of filtered bicarbonate and excretion of acid.”

Therefore, as you can see, an acidotic diet takes a greater toll on health as we age not just because of the fact that it is skewed towards an acid pH but because we lose the ability to excrete acid metabolites.


In the next section of the Pizzorno et al (1) paper several methods of clinical assessment are discussed.  The one I would like to feature in this monograph is the one about which we are all most familiar, urine pH.  The following quote discusses the value of measuring 24-hour urine pH:

“Another test often used to estimate net amount of acid produced daily (NEAP) is the 24 h urine pH.  Urinary pH represents an index of the diet-dependent net amount of acid excreted (NAE)…as well as the potential renal acid load (PRAL).  Additionally, urine pH can be adjusted to a target pH based on PRAL calculations for dietary intake.”

What about the value of first morning urine pH using pH strips?  As many of you know, I have been an advocate of this method of measurement as a useful, practical, and cost-effective gross screen for years. According to Pizzorno et al (1) what is its actual value:

“…pH strip measurement of the first voided urine was not found to be predictive of the NEAP reflected by the 24 h urine NAE.”

What does this mean in plain English?  pH of the first voided urine does not correlate well with findings from 24-hour urine measurements.  Does this mean that first-morning urine pH measurements are worthless?  In my opinion, no.  Why do I say this?  Even though first morning urine pH measurements using pH strips does not correlate well with more precise measurements of metabolic acids, significant anecdotal evidence supports the idea that these measurements are a gross indication to both the clinician and patient that, metabolically, the patient is trending towards a more acidotic physiology that may be playing a role in the creation of patient chief complaints.  Therefore, even though first morning urine pH measurements are not precise indicators, they can play a very effective role in alerting both the practitioner and patient that acid/alkaline balance requires attention.


In the next section of the paper Pizzorno et al (1) discuss ways of optimizing low-grade chronic metabolic acidosis.  This first quote provides an overview of the approaches taken by the authors:

“The normalization of a low-grade chronic metabolic acidosis has been accomplished by two methods: change in dietary patterns and alkaline supplementation.  Dietary factors that affect net acid production include quantity and type of protein intake, fruits and vegetables and table salt (sodium chloride).  Alkali supplementation is generally in the form of potassium or sodium bicarbonate or citrate.”

The next two quotes I would like to feature go into more detail about why excessive salt intake needs to be reduced with low-grade chronic metabolic acidosis:

“…increasing sodium chloride intake dose-dependently decreases blood pH and plasma bicarbonate levels, independent of the partial pressure of carbon dioxide (PCO2), creatinine clearance and dietary acid load.”

In addition:

“Subjects who are particularly sensitive to salt, generally defined as an increase of 3 to 5 mmHg for a given salt load, have more of a metabolic acidosis than those subjects who are salt resistant.  So, while everyone’s net acid load would improve by lowering their dietary salt intake, some individuals should benefit more than others from this dietary intervention.”

Next, the authors offer the following comment on supplementation:

“A number of supplemental interventions have also been used.  Salts of carbonic acid are available in a variety of formats.  These include sodium or potassium bicarbonate and calcium carbonate.  Alkali salts are also available as citrate, acetate, or hydroxides.”



As indicated in the following quote, bone density has been correlated with the intake of acid-producing foods:

“In an examination of over 1000 women between the ages of 45 and 54 years, a lower dietary intake of acid-producing foods correlated with greater spine and hip bone mineral density, as well as greater forearm bone mass, after adjusting for age, weight, height, and menstrual status.  In the Study of Osteoporotic Fractures Research cohort, over 1000 women aged 65+ years were enrolled in a prospective cohort study.  Those with a high dietary ratio of animal to vegetable protein intake (a marker for a greater NEAP) were found to have more rapid femoral neck bone loss and a greater risk of hip fracture than did those with a low ratio.”

Concerning alkali supplementation and its impact on bone health, the authors state the following:

“A number of trials have shown that the bone loss can be reversed by the addition of a base.  Potassium bicarbonate has been shown to improve calcium and phosphorus balance, reduce bone resorption rates, and mitigate the normally occurring age-related decline in growth hormone secretion.  Potassium citrate combined with calcium citrate may be more beneficial than either alone, as demonstrated in a cross-over trial on bone turnover in postmenopausal women.  Urinary calcium excretion and markers of bone health were improved with potassium citrate, more so in those consuming a high-Na diet.”

Kidney stones

Concerning the impact of diet-induced, low-grade chronic metabolic acidosis on kidney stone formation, Pizzorno et al (1) state the following:

“Also of clinical significance is the role metabolic acidosis plays in nephrolithiasis, and its potential connection to bone loss.  Urinary Ca excretion is directly proportional to NAE in both stone-formers and normal subjects.  In a study of nearly 200 renal stone-formers designed to identify the greatest risk factors for nephrolithiasis, it was the potential acid load of the diet which had the strongest association with stone risk.  The authors suggest ‘that a diet with a very low potential acid load should be encouraged in renal stone patients for the prevention of recurrent stones.  This result can be obtained by the restriction of animal proteins but also by abundant supplementation with vegetables and fruits’.  Potassium magnesium citrate has been shown to counter renal stone formation associated with immobilization and was associated with a significant increase in urinary pH.”

The next quote provides further information on the use of alkali supplementation with patients who form kidney stones:

“Unlike in the studies of healthy subjects, in both men and women with a history of forming Ca stones, a 2-year treatment with potassium citrate increased forearm bone mineral density in idiopathic Ca stone-formers, with the speculation that it was the alkali load that reduced bone resorption by buffering endogenous acid production.”


As you might expect, it seems like, sooner or later, no matter what subject I am writing about, the commentary will evolve to a discussion on muscle.  This newsletter is no exception.  Pizzorno et al (1) state the following about the relationship between alkali therapy and muscle health:

“Another area of interest is the use of alkaline therapy for improving muscle function, exercise capacity and reducing age-related muscle wasting.  Acidaemia has been shown to increase muscle degradation in patients on haemodialysis.  One epidemiological study of 384 healthy men and women aged 65+ years found a higher intake of foods rich in K (fruits and vegetables) was associated with greater lean muscle mass.  The authors speculated that ‘this association is likely to result from the fact that the ingestion of potassium-rich alkaline foods such as fruit and vegetables relieves the mild metabolic acidosis that occurs with the ingestion of a typical American diet’, and suggest that it is plausible that age-related muscle mass decline and sarcopenia may be prevented by the appropriate intake of alkaline K salts.

Potassium bicarbonate has been shown to neutralize the metabolic acidosis, and reduce urinary N wasting in postmenopausal women.”

Insulin resistance/diabetes

As you also might expect, there is a relationship between insulin metabolism and acid/alkaline dynamics.  Pizzorno et al (1) point out:

“There may also be a connection between insulin resistance and acid-base equilibrium, though this relationship is still speculative.  Insulin resistance has been associated with a lower urinary citrate excretion, and hypocitraturic patients show greater insulin resistance than normocitraturic Ca stone-formers.  Type 2 diabetes mellitus has been shown to increase the risk of uric acid stone formation, because it causes a lower urinary pH due to impaired kidney ammoniagenesis.”

Pizzorno et al (1) end their paper by pointing out that there is a lack of consensus among researchers and clinicians about acid/alkaline chemistry that has prevented clinical application from being more widespread.  Nevertheless, the available research in the subject makes a strong case that increased clinical emphasis is warranted:

“The lack of consensus for both qualitative and quantitative aspects of acid-base chemistry in physiological systems as well as measurement has caused considerable confusion for both researchers and clinicians.  This confusion has also complicated the search for cause and effect and made clinical application difficult and controversial.  Nonetheless, the available research makes a compelling case that diet-induced acidosis is a real phenomenon, has significant clinical relevance, may largely be prevented through dietary changes, and should be recognised and treated.”


Still another paper that discusses diet-induced low-grade metabolic acidosis is “Diet-induced low-grade chronic metabolic acidosis and clinical outcomes: A review” by Carnauba et al (2).  Since most of the information in the paper was covered by the Pizzorno et al (1) paper, I will only discuss selected sections of the Carnauba et al paper.

The first section I would like to feature goes into some detail about the dietary constituents that contribute to an acid or alkaline environment:

“Diet may contribute to low-grade metabolic acidosis through the ingestion of dietary constituents of non-volatile acids and bases.  The nutrients that release acid precursors into the bloodstream are phosphorus and proteins (mostly containing sulfur amino acids, such as cysteine, methionine, and taurine, and cationic amino acids such as lysine and arginine).  In addition, sodium chloride (NaCl) intake is reported to be an independent predictor of plasma bicarbonate concentration.  Assuming a causal relationship, NaCl may exert approximately 50-100% of the acidosis-producing effect of the dietary acidic load, and is therefore considered a predictor of diet-induced low-grade metabolic acidosis.  On the other hand, the nutrients that are precursors of bases are potassium, magnesium, and calcium.  Thus, in general, the main foods that release precursors of acids into the bloodstream are mostly of animal origin (except for beans and nuts) and foods that are precursors of bases are mainly of plant origin.”

What are the foods that contribute the most to an acidic scenario?  Carnauba et al (2) state:

“…the foods that contribute most to the release of acids into the bloodstream are meats (beef, pork, or poultry), eggs, beans, and oilseeds…”

Diet-induced low-grade metabolic acidosis and hypertension

One condition that can be related to diet-induced low-grade metabolic acidosis that was not mentioned in the Pizzorno et al (1) paper is hypertension.  Concerning this relationship Carnauba et al (2) state:

“The number of studies evaluating the association between dietary acid load and the risk of hypertension has increased in recent years.  Through cross-sectional analyses, research has shown that PRAL and NEAP are positively associated with increased values of diastolic blood pressure and systolic blood pressure in elderly individuals (n=673, ages 70-71 years) and in young women (n=1136, ages 18-22 years).”

The next quote provides some of the mechanisms that explain the relationship between a high acid diet and hypertension:

“Some mechanisms are suggested to justify the association between a high acid diet load and the risk of hypertension.  In the presence of low-grade metabolic acidosis, there is an increase in the pituitary stimulus for ACTH synthesis and a consequent production of cortisol and aldosterone, which in excess, may induce an increase in blood pressure.  In addition, the acid-base balance influences mineral homeostasis by regulating the calcium absorption in the kidneys, and it is reported that the increased urinary excretion of this mineral may be associated with an increased blood pressure.  In addition, NaCl intake, the most known risk factor associated with the etiology of hypertension, is an independent predictor of diet-induced low-grade metabolic acidosis.”


As I have been stating in this newsletter series, it is my opinion that issues relating to acid/alkaline balance have been significantly under appreciated by the health care community.  Interestingly, just the opposite is the issue of inflammation, which is recognized by virtually everyone in the health care community as a major contributor to almost every chronic illness.  Could there be a relationship between these two chronic illness issues that have been generally thought to be totally unrelated?  The paper “Metabolic acidosis treatment as part of a strategy to curb inflammation” by de Nadai et al (3) addresses this question.

The first quote I would like to feature from this paper suggests that, indeed, there is a profound relationship between metabolic acidosis and immune function:

“Metabolic acidosis is one of the most common abnormalities in patient suffering from serious diseases.  They have numerous etiologies and treatment of the underlying disease is the basis of therapy.  However, there is growing evidence suggesting acidosis itself has profound effects on the host, particularly in immune function.”

In support of this contention is the fact, as noted in the following quote, that there is a relationship between indicators of acidosis on routine blood chemistry and inflammatory markers:

“It was shown that a higher anion gap and a lower level of serum bicarbonate (despite being within the normal range) were associated with higher levels of several inflammatory biomarkers, including leukocyte count and levels of C-reactive protein.”

With the above in mind, the authors conclude:

“Most often, metabolic acidosis is present in the acute systemic inflammatory response in which the control of acid-base balance is part of the treatment protocol.  Thus, evaluation of the role of metabolic acidosis is mandatory.”

De Nadai et al (3) conclude their paper by providing a summary of key points concerning the relationship between metabolic acidosis and the inflammatory response.  Below are some of the most significant key points:

“i. Metabolic acidosis is one of the most common abnormalities in patients suffering from serious diseases, and there is growing evidence suggesting that acidosis itself has profound effects on the host, particularly in immune function.

  1. Recent evidence suggests that the different forms of acidosis (metabolic and respiratory) and even different types of metabolic acidosis (hyperchloremia and lactic) may produce different effects on immune function.
  2. Anion gap, bicarbonate, and lactate are possible biomarkers of the inflammation response.
  3. Perhaps the most unequivocal data providing evidence of the immune response impairment emerge from the clinical studies of the organic acidosis and ketoacidosis. In general, the clinical acidemias are accompanied by immunodeficiency, including a reduction in white cell numbers, gamma globulins, and mitogenic responses, and a diminution of the inflammatory response.

viii. The correction of metabolic acidosis as an isolated marker needs to be abandoned and considered as being an essential part of the systemic inflammatory response.  Is it better to consider ‘body acid-base-imbalance’ than ‘blood acid-base-imbalance’?”


As I have mentioned repeatedly, it is my opinion that acid/alkaline dynamics and fluid and electrolyte issues in general do not get the attention they deserve, certainly in the general health care community and, regrettably, too often in the clinical nutrition community.  Furthermore, those clinicians who do tend to focus on acid/alkaline imbalances in their chronically ill patients often consider it as an isolated entity with the idea that correction, generally in the form “alkalizing the patient,” will act as some sort of cure-all panacea.  As well emphasized in the last paper reviewed above by de Nadai et al (3), this important issue is best viewed as just one of many metabolic responses that are contributing to ill health.  Furthermore, they contribute to ill health not because they exist per se but because they have existed in excessive amounts for an excessive amount of time.

With the above in mind, I am not suggesting that you make fluid and electrolytes and acid/alkaline dynamics the central focus of your diagnostic and treatment regimen for chronically ailing patients at the expense of other key issues such as insulin resistance, inflammation, GI dysfunction, etc.  Rather, particularly for those chronically ill patients who are not responding to the usual interventions that revolve around addressing food allergies, identifying SNPs, instituting micronutrient supplementation, reducing inflammation, and optimizing GI, insulin, and cortisol function, don’t forget to look at acid/alkaline imbalances as well as the other underappreciated issues I have discussed in the past – muscle mass and function and optimal protein intake.

Moss Nutrition Report #286 – 07/01/2019 – PDF Version


  1. Pizzorno J et al. Diet-induced acidosis: is it real and clinically relevant? Br J Nutr. 2010;103:1185-94.
  2. Carnauba RA et al. Diet-induced low-grade metabolic acidosis and clinical outcomes: A review. Nutrients. 2017;9.
  3. de Nadai TR et al. Metabolic acidosis treatment as part of a strategy to curb inflammation. Int J Inflammation. 2013;2013.