Acid–base balance may influence risk for insulin resistance syndrome by modulating cortisol output

https://doi.org/10.1016/j.mehy.2004.01.045Get rights and content

Abstract

Frank metabolic acidosis is known to promote renal excretion of hydrogen ion by induction of glutaminase and other enzymes in the renal tubules. This induction, at least in part, reflects an increase in pituitary output of ACTH and a consequent increased production of cortisol and aldosterone; these latter hormones act on the renal tubules to promote generation of ammonia, which expedites renal acid excretion. Recent evidence suggests that the moderate metabolic acidosis associated with a protein-rich diet low in organic potassium salts – quantifiable by net acid output in daily urine – can likewise evoke a modest increase in cortisol production. Since cortisol promotes development of visceral obesity, and has a direct negative impact on insulin function throughout the body, even a modest sustained up-regulation of cortisol production may have the potential to increase risk for insulin resistance syndrome and type 2 diabetes. This thesis appears to be consistent with previous epidemiological reports correlating high potassium consumption, or a high intake of fruits and vegetables, with reduced risk for diabetes and coronary disease. Future prospective epidemiology should assess whether the estimated acid–base balance of habitual diets – calculated from the ratio of dietary protein and potassium – correlates with risk for insulin resistance syndrome and diabetes.

Section snippets

Acid–base balance as a determinant of cortisol production

Remer and colleagues [1], in a crossover study examining physiological effects of three diets – a “normal protein” omnivore diet, a higher protein omnivore diet, and a relatively low protein lactovegetarian diet (50 g protein daily) – found that 24-h urinary excretion of cortisol was about 30% lower (p<0.01) on the latter diet than on the normal protein diet. Conversely, this parameter trended higher on the high-protein as compared to the normal protein diet, though this difference did not

Cortisol modulation of insulin function

It is clear that prolonged frank hyperglucocorticoidism – as seen in Cushing's syndrome, or during clinical use of high-dose glucocorticoids – tends to promote visceral obesity, compromises insulin sensitivity, and increases risk for insulin resistance syndrome and diabetes. Although glucocorticoids can act directly on skeletal muscle to compromise its insulin responsiveness, induction of global insulin resistance syndrome may reflect an impact of glucocorticoids on adipocytes – most notably

An “alkaline diet” may decrease risk for insulin resistance syndrome

These considerations suggest the intriguing possibility that – other factors being equal – a diet which promotes an acidic metabolic environment will tend to promote visceral obesity and insulin resistance syndrome via a modest up-regulation of cortisol production – whereas diets promoting a more alkaline metabolic environment may be protective in this regard. Of course, countervailing factors may come into play – notably, a diet quite high in protein, while acidifying, also has a favorable

References (56)

  • K.N. Frayn

    Non-esterified fatty acid metabolism and postprandial lipaemia

    Atherosclerosis

    (1998)
  • P. Bjorntorp

    Body fat distribution, insulin resistance, and metabolic diseases

    Nutrition

    (1997)
  • J.R. Seckl et al.

    Glucocorticoids, 11β-hydroxysteroid dehydrogenase, and fetal programming

    Kidney Int

    (2000)
  • J.S. Hannah et al.

    Postingestional effects of a high-protein diet on the regulation of food intake in monkeys

    Am. J. Clin. Nutr

    (1990)
  • G.A. Colditz et al.

    Diet and risk of clinical diabetes in women

    Am. J. Clin. Nutr

    (1992)
  • D.E. Williams et al.

    Frequent salad vegetable consumption is associated with a reduction in the risk of diabetes mellitus

    J. Clin. Epidemiol

    (1999)
  • S. Liu et al.

    Fruit and vegetable intake and risk of cardiovascular disease: the Women's Health Study

    Am. J. Clin. Nutr

    (2000)
  • T. Remer

    Dietary protein and fiber intake and sex hormone-binding globulin

    J. Clin. Endocrinol. Metab

    (2001)
  • C. Longcope et al.

    Diet and sex hormone-binding globulin

    J. Clin. Endocrinol. Metab

    (2000)
  • T. Remer et al.

    Short-term impact of a lactovegetarian diet on adrenocortical activity and adrenal androgens

    J. Clin. Endocrinol. Metab

    (1998)
  • M. Maurer et al.

    Neutralization of Western diet inhibits bone resorption independently of K intake and reduces cortisol secretion in humans

    Am. J. Physiol. Renal Physiol

    (2003)
  • T.C. Welbourne

    Acidosis activation of the pituitary-adrenal-renal glutaminase I axis

    Endocrinology

    (1976)
  • Z. Karim et al.

    Renal handling of NH4+ in relation to the control of acid–base balance by the kidney

    J. Nephrol

    (2002)
  • T.C. Welbourne et al.

    Influence of aldosterone on renal ammonia production

    Am. J. Physiol

    (1977)
  • G.O. Perez et al.

    The effect of acute metabolic acidosis on plasma cortisol, renin activity and aldosterone

    Horm. Res

    (1979)
  • T. Remer

    Influence of diet on acid–base balance

    Semin. Dial

    (2000)
  • T. Remer

    Influence of nutrition on acid–base balance – metabolic aspects

    Eur. J. Nutr

    (2001)
  • K.L. Tucker et al.

    The acid–base hypothesis: diet and bone in the Framingham Osteoporosis Study

    Eur. J. Nutr

    (2001)
  • Cited by (35)

    • Therapeutic implications of hypothalamic-pituitaryadrenal-axis modulation in Alzheimer's disease: A narrative review of pharmacological and lifestyle interventions

      2021, Frontiers in Neuroendocrinology
      Citation Excerpt :

      Such diets (usually western) are typically acidogenic, high in animal protein and low in fruits and vegetables, causing a sub-clinical state of metabolic acidosis (Cordain et al., 2005). Among other negative health related effects, acidosis can also influence adrenal hormone production of cortisol whereby studies have reported a consequential increase of salivary and serum cortisol (Gibson et al., 1999) alongside an increased risk of insulin resistance and type 2 diabetes (McCarty, 2005). Epidemiological evidence has shown that adherence to diet comprised of high vegetable intake, whole grains, fish and moderate intake of saturated fats, refined sugar and salt reduced urinary cortisol levels and elevated DHEAS among Puerto Rican women (n = 1381), but not among men (Mattei et al., 2013).

    • Higher dietary acid load is weakly associated with higher adiposity measures and blood pressure in Japanese adults: The National Health and Nutrition Survey

      2017, Nutrition Research
      Citation Excerpt :

      The potential importance of metabolic acidosis (without acidemia) to metabolic risk factors has been recently suggested in the literature [1-3].

    • Lowered extracellular pH is involved in the pathogenesis of skeletal muscle insulin resistance

      2014, Biochemical and Biophysical Research Communications
      Citation Excerpt :

      The organic acids-induced acidosis could contribute to the development of insulin resistance. Several studies [20–22] have suggested a close correlation between organic acid production and insulin sensitivity in both type 2 DM patients and healthy subjects. Recent epidemiological studies have confirmed that the relationship between insulin resistance and metabolic acidosis-caused phenomena, such as low serum bicarbonate and low urine pH [6].

    • Improvement of insulin resistance, blood pressure and interstitial pH in early developmental stage of insulin resistance in OLETF rats by intake of propolis extracts

      2013, Biochemical and Biophysical Research Communications
      Citation Excerpt :

      The organic acids-induced acidosis could contribute to the development of insulin resistance. Several studies [24–26] have suggested a close correlation of organic acid production with insulin sensitivity in both type 2 diabetes patients and healthy subjects. Lower levels of serum bicarbonate and higher levels of anion gap resulted from metabolic acidosis were associated with lower insulin sensitivity [27].

    • Acidosis, phosphofructokinase, and diabetic coma [2]

      2009, British Journal of Anaesthesia
    View all citing articles on Scopus
    View full text