The Role of the Diet’s Net Acid Load in Aging Pedro Carrera Bastos Sevilla October 25, 2009
<ul><li>2000:  </li></ul><ul><li>4 million new fractures </li></ul><ul><li>Total direct costs:  </li></ul><ul><li>~€31.7 b...
Arterial blood PH Rose BD, Post TW.  Clinical Physiology of Acid-base and Electrolyte Disorders . McGraw-Hill, 2001. pH = ...
<ul><li>Over the usual physiological ranges of pulmonary and renal acid-base regulatory function, and over the range of ty...
<ul><li>Age  also determines [H+]b set-point, in part by affecting the integrity of renal function. </li></ul>Frassetto L,...
Net Endogenous Acid Production
NEAP <ul><li>  NEAP  =  Production rate of sulfuric acid  +  Production rate of  Organic Acids  -  Production rate of  Bic...
Net Acid Load for some foods Net base yielding Net Acid yielding PRAL  (mEq/100 kcal) NEUTRAL Frassetto L.A. et al.   J Ne...
<ul><li>NaCl has ~  50%  of the acidosis-producing effect of the diet net acid load </li></ul>
Why is this relevant???
<ul><li>In the steady state,   </li></ul><ul><ul><li>R enal Net Acid Excretion (RNAE) = NEAP  </li></ul></ul>A substantial...
<ul><li>“ In order to maintain electrical neutrality,  retention of H+ entails loss of other positive ions from the body  ...
<ul><li>Example: </li></ul><ul><li>Loss of calcium ions  caused by  mobilization of alkaline salts of bone  to titrate som...
<ul><li>“ The daily net acid retention needed to sustain skeletal demineralization in the long run need only amount to a v...
Pathophysiologic consequences  of  severe metabolic acidosis in humans
Chronic acidosis and bone health
<ul><li>Bone is a large reservoir of base  in the form of alkaline salts of calcium (phosphates, carbonates) </li></ul><ul...
<ul><li>The liberated calcium and phosphorus are lost in the urine , without compensatory increase in gastrointestinal abs...
<ul><li>In  chronic acid loading studies  in humans : </li></ul><ul><ul><li>Urinary hydroxyproline excretion increases </l...
<ul><li>Extracellular acidification increases  the activity of osteoclasts & suppresses the activity of osteoblasts </li><...
Chronic acidosis and skeletal muscle nitrogen metabolism
<ul><li>In chronic metabolic acidosis: </li></ul><ul><li>P rotein degradation in skeletal muscle is accelerated , which in...
Glutamine Acid Excretion Amonia  (NH 4 ) > Urinary Acceptor of H+ Frassetto L, et al.  Eur J Nutr . 2001 Oct;40(5):200-13
<ul><li>Acidosis-induced proteolysis appears to be an acid-base homeostatic mechanism   </li></ul>Frassetto L, et al.  Eur...
Other adverse consequences of Chronic Metabolic acidosis
<ul><li>   Increase in urinary calcium </li></ul><ul><li>   Reduction in urinary citrate </li></ul>Kidney Stones Mild re...
<ul><li>Experimentally induced, chronic  metabolic acidosis in humans: </li></ul><ul><li>   Hepatocellular resistance to ...
Chronic low-grade  diet-induced  Metabolic Acidosis
<ul><li>“ It is understandably difficult to think metabolic acidosis when the values for plasma acid-base composition are ...
<ul><li>“ Such acidosis-induced pathophysiological conditions  as negative calcium and phosphorus balance, accelerated bon...
Bone health
Neutralization of dietary acid load  for 7 days  in nine healthy subjects (6 men, 3 women)  induced a  significant cumulat...
Frassetto L, Morris RC Jr, Sebastian A.  J Clin Endocrinol Metab . 2005 Feb;90(2):831-4.  KBC treatment induced a dose-dep...
The addition of oral potassium citrate to a high-salt diet prevented the increased excretion of urine calcium and the bone...
<ul><li>Neutralization of the dietary acid load with K-citrate  and KHCO3:  </li></ul><ul><li>   Reduce the urinary excre...
Lower  estimates of energy-adjusted  NEAP  were correlated with  greater spine and hip BMD  and greater forearm bone mass
 
Children with a higher dietary PRAL had  significantly less cortical area  (P  0.05)  and bone mineral content  (P  0.01).
Low nutritional acid load  was correlated with higher BMD at the heel in very elderly women with a fracture history
 
Fruit and vegetable intake  may protect against premenopausal bone loss
High fruit and vegetable intakes have beneficial effects on the bone area of the radius and whole body in early   pubertal...
12-y-old girls consuming  high amounts of fruit  had significantly  higher heel BMD  than did the  moderate fruit consumers
Appropriate intakes of  vegetables and fruit have a beneficial effect on TBBMC in boys  aged 8–20 y
Higher fruit and vegetable intakes  may have positive effects on bone mineral status  in both younger and older age groups...
Cola intake  was associated with significantly  lower BMD at each hip site , but not the spine,  in women  but not in men
Bicarbonate-rich alkali mineral  waters with low potential renal acid load values were shown to decrease bone resorption m...
Jajoo R, et al.  J Am Coll Nutr . 2006 Jun;25(3):224-30.
Skeletal muscle nitrogen metabolism
<ul><ul><li>14  Post-Menopausic Women (for > 5 y + no HRT). </li></ul></ul><ul><ul><li>Age: 51-77 y / Weight: 53-76 kg / B...
<ul><ul><li>Urinary N decreased 14 g in 18 days </li></ul></ul><ul><ul><ul><li>1 kg of LBM = 32 g of N     </li></ul></ul...
Higher excretion of  potassium  is associated with  greater %LBM  in healthy older men and women “ The positive associatio...
Other consequences
Net Endogenous Acid Production  was positively associated with  excretions of magnesium and calcium
Potentially bioactive free glucocorticoids are  metabolically  affected by diet-dependent net  endogenous acid production ...
<ul><li>Serum GH concentration increased:  </li></ul><ul><ul><li>From  826±548 pg/ml  before KHCO3 </li></ul></ul><ul><ul>...
Frassetto LA, et al.  J Nutr . 2008 Feb;138(2):419S-422S
NEAP in pre-agricultural diets Sebastian A, et al.  Am J Clin Nutr . 2002 Dec;76(6):1308-16   159 HG societies 87% NEAP <0
EDNP –   Empty calories   (oils, added fats & sugar) . Frassetto L.A. et al.   J Nephrol . 2006 Mar-Apr;19 Suppl 9:S33-40
 
British Medical Association &quot;Compared with current diets, the pre-agricultural hunter-gatherer diets of our Palaeolit...
Thank you Special thanks to  Prof. Loren Cordain , of Colorado State University
Pedro Carrera Bastos [email_address] www.nutriscience.pt
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The role of the diet’s net acid load in aging

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The Diet\'s Net Acid Load is, in part, responsible for the age-related loss of bone and skeletal muscle mass

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The role of the diet’s net acid load in aging

  1. 1. The Role of the Diet’s Net Acid Load in Aging Pedro Carrera Bastos Sevilla October 25, 2009
  2. 2. <ul><li>2000: </li></ul><ul><li>4 million new fractures </li></ul><ul><li>Total direct costs: </li></ul><ul><li>~€31.7 billion </li></ul>Osteoporosis in Europe Johnell O, Kanis JA. Osteoporos Int 2006; 17:1726 Janssen I, et al. J Am Geriatr Soc . 2004 Jan;52(1):80-5. Sarcopenia in US <ul><li>2000: </li></ul><ul><li>Total direct costs: </li></ul><ul><li>$18.5 billion </li></ul>
  3. 3. Arterial blood PH Rose BD, Post TW. Clinical Physiology of Acid-base and Electrolyte Disorders . McGraw-Hill, 2001. pH = 7,62 + log HCO 3 - /PCO 2 (Henderson-Hasselbach)   pH H+ (nanoeq/L) PCO2 mmHg HCO3- (mEq/L) Arterial blood 7,37-7,43 37-43 36-44 22-26
  4. 4. <ul><li>Over the usual physiological ranges of pulmonary and renal acid-base regulatory function, and over the range of typical Western diet compositions, PCO2 has the greatest impact on blood hydrogen ion concentration set-point . </li></ul>Rose BD, Post TW. Clinical Physiology of Acid-base and Electrolyte Disorders . McGraw-Hill, 2001. Gennari FJ, et al . Acid-Base Disorders and their treatment . Tailor & Francis, 2005 Frassetto L.A. et al. J Nephrol . 2006 Mar-Apr;19 Suppl 9:S33-40
  5. 5. <ul><li>Age also determines [H+]b set-point, in part by affecting the integrity of renal function. </li></ul>Frassetto L, Morris RC, Jr., Sebastian A. Am J Physiol 1996 (271):1114–1122
  6. 6. Net Endogenous Acid Production
  7. 7. NEAP <ul><li> NEAP = Production rate of sulfuric acid + Production rate of Organic Acids - Production rate of Bicarbonate </li></ul><ul><li>Production rate of sulfuric acid: From the metabolism of dietary sulfur-containing amino acids </li></ul><ul><li>Production rate of Organic Acids: From incomplete combustion of carbohydrate and fat </li></ul><ul><li>Production rate of Bicarbonate = </li></ul><ul><li>= ∑ inorganic cations - ∑ i norganic anions </li></ul><ul><ul><ul><ul><li>Each corrected for fractional intestinal absorption </li></ul></ul></ul></ul><ul><li>PB = 0.95 Na + + 0.8 K + + 0.25 Ca 2+ + 0.32 Mg 2+ - 0.95 Cl - - 0.63 Pi </li></ul>Sebastian A, et al. Am J Clin Nutr . 2002 Dec;76(6):1308-16 NEAP = Production rate of sulfuric acid + Production rate of Organic Acids - Production rate of Bicarbonate
  8. 8. Net Acid Load for some foods Net base yielding Net Acid yielding PRAL (mEq/100 kcal) NEUTRAL Frassetto L.A. et al. J Nephrol . 2006 Mar-Apr;19 Suppl 9:S33-40. PRAL (mEq/100 kcal) PRAL (mEq/100 kcal) Fish 14,6 Meat 12,4 Poultry 7,8 Egg 7,3 Shellfish 7,3 Cheese 3,3 Milk 1,3 Cereals 1,1 Nuts -1,1 Fruit -5,2 Tubers -5,4 Mushrooms -11,2 Root vegetables -17,1 Tomato -17,5 Vegetables -23,4 Legumes -0,4
  9. 9. <ul><li>NaCl has ~ 50% of the acidosis-producing effect of the diet net acid load </li></ul>
  10. 10. Why is this relevant???
  11. 11. <ul><li>In the steady state, </li></ul><ul><ul><li>R enal Net Acid Excretion (RNAE) = NEAP </li></ul></ul>A substantial fraction of the population habitually ingests a diet yielding NEAPs > 40 meq/day Frassetto L.A. et al. J Nephrol . 2006 Mar-Apr;19 Suppl 9:S33-40. NEAP > 40 meq/day  RNAE < NEAP (The body appears to retain H+ as NEAP increases)
  12. 12. <ul><li>“ In order to maintain electrical neutrality, retention of H+ entails loss of other positive ions from the body ” </li></ul>Frassetto L.A. et al. J Nephrol . 2006 Mar-Apr;19 Suppl 9:S33-40
  13. 13. <ul><li>Example: </li></ul><ul><li>Loss of calcium ions caused by mobilization of alkaline salts of bone to titrate some of the retained H+ </li></ul>Frassetto L.A. et al. J Nephrol . 2006 Mar-Apr;19 Suppl 9:S33-40
  14. 14. <ul><li>“ The daily net acid retention needed to sustain skeletal demineralization in the long run need only amount to a very small fraction of the daily diet dependent NEAP. An amount that might easily escape detection by current methodologies for determining net acid balance .” </li></ul>Frassetto L.A. et al. J Nephrol . 2006 Mar-Apr;19 Suppl 9:S33-40
  15. 15. Pathophysiologic consequences of severe metabolic acidosis in humans
  16. 16. Chronic acidosis and bone health
  17. 17. <ul><li>Bone is a large reservoir of base in the form of alkaline salts of calcium (phosphates, carbonates) </li></ul><ul><ul><li>Those salts are mobilized and released into the systemic circulation in response to increased loads of acid . </li></ul></ul><ul><ul><ul><li>The liberated base mitigates the severity of the attendant systemic acidosis , contributing to systemic acid-base homeostasis . </li></ul></ul></ul>Frassetto L, et al. Eur J Nutr . 2001 Oct;40(5):200-13
  18. 18. <ul><li>The liberated calcium and phosphorus are lost in the urine , without compensatory increase in gastrointestinal absorption, and reduce bone mineral content </li></ul>Frassetto L, et al. Eur J Nutr . 2001 Oct;40(5):200-13
  19. 19. <ul><li>In chronic acid loading studies in humans : </li></ul><ul><ul><li>Urinary hydroxyproline excretion increases </li></ul></ul><ul><ul><li>Serum osteocalcin levels decreases </li></ul></ul><ul><ul><li>Suggesting that matrix resorption increased and formation decreased </li></ul></ul>Frassetto L, et al. Eur J Nutr . 2001 Oct;40(5):200-13
  20. 20. <ul><li>Extracellular acidification increases the activity of osteoclasts & suppresses the activity of osteoblasts </li></ul><ul><ul><li>Release of bone mineral by osteoclasts is accompanied by osteoclastic degradation of bone matrix. </li></ul></ul><ul><ul><li>Serum osteocalcin levels decreases </li></ul></ul>Frassetto L, et al. Eur J Nutr . 2001 Oct;40(5):200-13
  21. 21. Chronic acidosis and skeletal muscle nitrogen metabolism
  22. 22. <ul><li>In chronic metabolic acidosis: </li></ul><ul><li>P rotein degradation in skeletal muscle is accelerated , which increases the production of nitrogen end-products that are eliminated in the urine, without commensurately increasing the rate of protein synthesis , thereby inducing </li></ul><ul><li>negative nitrogen balance </li></ul>Frassetto L, et al. Eur J Nutr . 2001 Oct;40(5):200-13
  23. 23. Glutamine Acid Excretion Amonia (NH 4 ) > Urinary Acceptor of H+ Frassetto L, et al. Eur J Nutr . 2001 Oct;40(5):200-13
  24. 24. <ul><li>Acidosis-induced proteolysis appears to be an acid-base homeostatic mechanism </li></ul>Frassetto L, et al. Eur J Nutr . 2001 Oct;40(5):200-13 By releasing increased amounts of amino acids, including glutamine and amino acids that the liver can convert to glutamine , which is the major nitrogen source used by the kidney for synthesis of ammonia, the kidney can increase the excretion of acid (as ammonium ion) in the urine, thereby mitigating the severity of the acidosis
  25. 25. Other adverse consequences of Chronic Metabolic acidosis
  26. 26. <ul><li> Increase in urinary calcium </li></ul><ul><li> Reduction in urinary citrate </li></ul>Kidney Stones Mild reductions of plasma [HCO3 –] and arterial Ph to values still within their normal range Frassetto L.A. et al. J Nephrol . 2006 Mar-Apr;19 Suppl 9:S33-40
  27. 27. <ul><li>Experimentally induced, chronic metabolic acidosis in humans: </li></ul><ul><li> Hepatocellular resistance to growth hormone </li></ul><ul><li> Reduction in serum IGF-1 levels </li></ul>Frassetto L, et al. Eur J Nutr . 2001 Oct;40(5):200-13
  28. 28. Chronic low-grade diet-induced Metabolic Acidosis
  29. 29. <ul><li>“ It is understandably difficult to think metabolic acidosis when the values for plasma acid-base composition are in the range traditionally considered normal” </li></ul>Frassetto L, et al. Eur J Nutr . 2001 Oct;40(5):200-13
  30. 30. <ul><li>“ Such acidosis-induced pathophysiological conditions as negative calcium and phosphorus balance, accelerated bone resorption, and renal nitrogen wasting appear to be consequences of the normal diet acid load , as they are significantly improved by “normalizing” blood acid-base composition by neutralizing the diet net acid load with small amounts of exogenous base ” </li></ul>Frassetto L, et al. Eur J Nutr . 2001 Oct;40(5):200-13
  31. 31. Bone health
  32. 32. Neutralization of dietary acid load for 7 days in nine healthy subjects (6 men, 3 women) induced a significant cumulative calcium retention and significantly reduced the urinary excretion of deoxypyridinoline, pyridinoline, and n-telopeptide
  33. 33. Frassetto L, Morris RC Jr, Sebastian A. J Clin Endocrinol Metab . 2005 Feb;90(2):831-4. KBC treatment induced a dose-dependent decrease in UCaV/Cr that persisted up to 36 months, with the greatest decreases occurring in those women with the greatest baseline UCaV
  34. 34. The addition of oral potassium citrate to a high-salt diet prevented the increased excretion of urine calcium and the bone resorption marker caused by a high salt intake.
  35. 35. <ul><li>Neutralization of the dietary acid load with K-citrate and KHCO3: </li></ul><ul><li> Reduce the urinary excretion of calcium </li></ul><ul><li>Decrease bone resorption </li></ul><ul><li>Increase bone formation </li></ul>Sebastian A, et al. N Engl J Med 1994; 330: 1776-81 Frassetto L, Morris RC Jr, Sebastian A. J Clin Endocrinol Metab 2005 (90): 831–834 Dawson-Hughes B, et al. J Clin Endocrinol Metab . 2009 Jan;94(1):96-102
  36. 36. Lower estimates of energy-adjusted NEAP were correlated with greater spine and hip BMD and greater forearm bone mass
  37. 38. Children with a higher dietary PRAL had significantly less cortical area (P 0.05) and bone mineral content (P 0.01).
  38. 39. Low nutritional acid load was correlated with higher BMD at the heel in very elderly women with a fracture history
  39. 41. Fruit and vegetable intake may protect against premenopausal bone loss
  40. 42. High fruit and vegetable intakes have beneficial effects on the bone area of the radius and whole body in early pubertal girls . The lower urinary calcium output associated with higher fruit and vegetable intakes may be a modulating factor.
  41. 43. 12-y-old girls consuming high amounts of fruit had significantly higher heel BMD than did the moderate fruit consumers
  42. 44. Appropriate intakes of vegetables and fruit have a beneficial effect on TBBMC in boys aged 8–20 y
  43. 45. Higher fruit and vegetable intakes may have positive effects on bone mineral status in both younger and older age groups, especially at the spine and femoral neck.
  44. 46. Cola intake was associated with significantly lower BMD at each hip site , but not the spine, in women but not in men
  45. 47. Bicarbonate-rich alkali mineral waters with low potential renal acid load values were shown to decrease bone resorption markers and even parathyroid hormone levels
  46. 48. Jajoo R, et al. J Am Coll Nutr . 2006 Jun;25(3):224-30.
  47. 49. Skeletal muscle nitrogen metabolism
  48. 50. <ul><ul><li>14 Post-Menopausic Women (for > 5 y + no HRT). </li></ul></ul><ul><ul><li>Age: 51-77 y / Weight: 53-76 kg / BMI: 21-28kg/m2 </li></ul></ul><ul><ul><li>2 week adaptation period to a positive Net acid yielding diet </li></ul></ul><ul><ul><li>Administration of Potassium Bicarbonate for 18 days </li></ul></ul><ul><ul><li>Follow-up of 12 days after the intervention </li></ul></ul>
  49. 51. <ul><ul><li>Urinary N decreased 14 g in 18 days </li></ul></ul><ul><ul><ul><li>1 kg of LBM = 32 g of N  </li></ul></ul></ul><ul><ul><ul><li>14 g of N = 0,43 kg of LBM in 18 days </li></ul></ul></ul>Frassetto L, Morris RC Jr, Sebastian A. J Clin Endocrinol Metab . 1997 Jan;82(1):254-9
  50. 52. Higher excretion of potassium is associated with greater %LBM in healthy older men and women “ The positive association of potassium with %LBM may be related to the neutralizing effect of increased ingestion of potassium salts on the mild metabolic acidosis resulting from habitual ingestion of a typical net acid–producing American diet ”
  51. 53. Other consequences
  52. 54. Net Endogenous Acid Production was positively associated with excretions of magnesium and calcium
  53. 55. Potentially bioactive free glucocorticoids are metabolically affected by diet-dependent net endogenous acid production This elevation in cortisol can be attenuated when NEAP is neutralized via bicarbonate supplementation or a low net acid-yielding diet Maurer M, et al. Am J Physiol Renal Physiol 2003, 284:F32-40. Remer T, Pietrzik K, Manz F. J Clin Endocrinol Metab 1998, 83:2132-7.
  54. 56. <ul><li>Serum GH concentration increased: </li></ul><ul><ul><li>From 826±548 pg/ml before KHCO3 </li></ul></ul><ul><ul><li>To 915±631 pg/ml after KHCO3 </li></ul></ul>
  55. 57. Frassetto LA, et al. J Nutr . 2008 Feb;138(2):419S-422S
  56. 58. NEAP in pre-agricultural diets Sebastian A, et al. Am J Clin Nutr . 2002 Dec;76(6):1308-16 159 HG societies 87% NEAP <0
  57. 59. EDNP – Empty calories (oils, added fats & sugar) . Frassetto L.A. et al. J Nephrol . 2006 Mar-Apr;19 Suppl 9:S33-40
  58. 61. British Medical Association &quot;Compared with current diets, the pre-agricultural hunter-gatherer diets of our Palaeolithic ancestors were based on wild animal and plant foods and were much higher in protein and lower in carbohydrate &quot; &quot;Humans evolved to consume a diet very different from that consumed by many people today. This makes our physiology potentially mismatched to our contemporary lifestyles, increasing the risks of ill health .&quot; February 2009 Early life nutrition and lifelong health Hanson M, Fall C, Robinson S, Baird J. Early life nutrition and lifelong health , BMA, 2009 Feb
  59. 62. Thank you Special thanks to Prof. Loren Cordain , of Colorado State University
  60. 63. Pedro Carrera Bastos [email_address] www.nutriscience.pt

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