PRAL, Mortality Risk, and Lifespan

Within the body, meat, grains, and nuts are generally acid-forming, whereas vegetables and fruits are alkaline-forming. Is the distinction between whether your diet is acid- or alkaline-forming important for optimal health and lifespan? In an earlier post, I discussed the importance of PRAL (potential renal acid load) by correlating it with serum bicarbonate and mortality risk (https://michaellustgarten.wordpress.com/2016/02/07/using-diet-to-optimize-circulating-biomarkers-serum-bicarbonate/).

More recent data (a 15-year study of 81, 697 older adults; average age ~61y; Xu et al. 2016) has examined the association between PRAL with risk of death from all causes. In women, acidic PRAL values ( > 0) were associated with a significantly increased risk of death from all causes, as were alkaline PRAL values (< -5.6). In addition, very acidic (~40) and very alkaline (-30) PRAL values were associated with the highest risk for all-cause mortality:

pral-acm-men

Similarly, in men, when compared with a PRAL = 0, both alkaline (PRAl < -5.6) and acidic (> 29.8) values were associated with increased all-cause mortality risk.

pral-acm-women

While this data suggests that eating too much meat, grains, and/or nuts may not be optimal for health, it also suggests that eating too much alkaline-forming food, including veggies and fruits, may also not be optimal! My high veggie-based diet yields a very negative PRAL, ~-120 (~ -0.05 PRAL units/calorie), which would seem to put me at increased all-cause mortality risk. To further investigate, I decided to look at the PRAL values of long-lived societies.

The PRAL formula, as reported by Remer and Manz (1994) is:

PRAL = (0.49 * protein intake in g/day) + (0.037 * phosphorus intake in mg/day) – (0.02 * potassium intake in mg/day) – (0.013 * calcium intake in mg/day) – (0.027 * magnesium intake in mg/day).

Life expectancy for Seventh-Day Adventist women is 85 years, a value that is the highest in the world (Fraser and Shavlik 2001). What’s the average daily PRAL value for that population?

  • Average daily dietary data in both vegetarian and non-vegetarian Seventh-Day Adventist women (average age, ~72y) has been reported (Nieman et al. 1989). For vegetarians, total calories = 1452; protein = 47g; phosphosphorus = 889 mg; potassium = 2628 mg; calcium = 628 mg; magnesium = 283 mg. These values yield an alkaline PRAL = -33.2. Because higher amounts of these nutrients can result from an increased calorie intake, it’s important to divide PRAL by the average daily calorie value, thereby yielding  PRAL/calorie. For vegetarian Adventists, this value = -0.02.
  • In non-vegetarian Adventists, total calories = 1363; protein = 55g; phosphosphorus = 892 mg; potassium = 2342 mg; calcium = 633 mg; magnesium = 228 mg. These values also yield an alkaline PRAL = -25.5, and PRAL/calorie = -0.019.

Life expectancy for those who live on the island of Okinawa is among the longest in the world (Miyagi et al. 2003). What’s the average daily PRAL value for Okinawan older adults?

  • The average daily dietary data for 75-year old Okinawans  has been reported (Willcok et al. 2007): total calories, 1785; protein, 39g; phosphosphorus, 864 mg; potassium, 5200 mg; calcium, 505 mg; magnesium, 396 mg. These values also yield an  yield a very alkaline PRAL value = -87.4, and PRAL/calorie =  -0.049. Interestingly, these values are very close to my very alkaline PRAL values of -121, and PRAL/calorie = ~-0.05!

My goal is not just to get to 75 in great health, but to live past 100 (and far beyond). What’s the data in centenarians? Unfortunately, I could only find 2 studies that included dietary data for that age group.

  • In a study of 30 Chinese centenarians (average age, 103y), daily dietary values of 1220 calories, 39g protein, 603 mg phosphorus, 1433 mg potassium, 482 mg calcium, and 355 mg magnesium were reported (Cai et al. 2016), thereby yielding an average daily PRAL value = -20.3, and PRAL/calorie = -0.017.
  • Similarly, in a larger study of 104 Japanese centenarians (average age, 100y), daily dietary values of 1137 calories, 44g protein, 676 mg phosphorus, 1695 mg potassium, 414 mg calcium, and 154 mg magnesium were reported (Shimizu et al. 2003), thereby yielding an average daily PRAL value = -16.3, and PRAL/calorie = -0.014.

In contrast to the data of Xu et al. (2016), these data suggest that an alkaline diet may indeed be optimal for lifespan.

So what’s your dietary PRAL value?

If you’re interested, please have a look at my book!

References

Cai D, Zhao S, Li D, Chang F, Tian X, Huang G, Zhu Z, Liu D, Dou X, Li S, Zhao M, Li Q.  Nutrient Intake Is Associated with Longevity Characterization by Metabolites and Element Profiles of Healthy Centenarians. Nutrients. 2016 Sep 19;8(9).

Fraser GE, Shavlik DJ. Ten years of life: Is it a matter of choice? Arch Intern Med. 2001 Jul 9;161(13):1645-52.

Miyagi S, Iwama N, Kawabata T, Hasegawa K. Longevity and diet in Okinawa, Japan: the past, present and future. Asia Pac J Public Health. 2003;15 Suppl:S3-9.

Nieman DC, Underwood BC, Sherman KM, Arabatzis K, Barbosa JC, Johnson M, Shultz TD. Dietary status of Seventh-Day Adventist vegetarian and non-vegetarian elderly women. J Am Diet Assoc. 1989 Dec;89(12):1763-9.

Remer T, Manz F. Estimation of the renal net acid excretion by adults consuming diets containing variable amounts of protein. Am J Clin Nutr. 1994;59:1356-1361.

Shimizu K, Takeda S, Noji H, Hirose N, Ebihara Y, Arai Y, Hamamatsu M, Nakazawa S, Gondo Y, Konishi K. Dietary patterns and further survival in Japanese centenarians. J Nutr Sci Vitaminol (Tokyo). 2003 Apr;49(2):133-8.

Willcox BJ, Willcox DC, Todoriki H, Fujiyoshi A, Yano K, He Q, Curb JD, Suzuki M. Caloric restriction, the traditional Okinawan diet, and healthy aging: the diet of the world’s longest-lived people and its potential impact on morbidity and life span. Ann N Y Acad Sci. 2007 Oct;1114:434-55.

Xu H, Åkesson A, Orsini N, Håkansson N, Wolk A, Carrero JJ. Modest U-Shaped Association between Dietary Acid Load and Risk of All-Cause and Cardiovascular Mortality in Adults. J Nutr. 2016 Aug;146(8):1580-5.

Blood Testing: What’s An Optimal Value For Triglycerides?

In terms of all-cause mortality risk, is the reference range for circulating triglycerides (TG, <150 mg/dL) optimal?

A meta-analysis of 38 studies in 360,556 subjects with a median age of 48y and a 12-year follow-up reported lowest all-cause mortality risk for subjects with TG values less than 90 mg/dL (equivalent to ~1 mmol; Liu et al. (2013)). As shown below, each successive 90 mg/dL increase was associated with a 12% higher all-cause mortality risk. A person with a value closer to the high end of the reference range, ~150 would have a ~7% increased mortality risk compared someone with a value ~90. In other words, there would be 7 more deaths per 100 total people at a TG value of 150, compared with the death rate for people with values less than 90.

tg mortal

Added importance for the association between TG values less than 90 with all-cause mortality risk come from studies of people who have lived longer than 100 years, centenarians. As shown below, triglyceride values less than 101 mg/dL have been reported in 9 of 11 centenarian studies:

tg mort

What’s my TG value? On my latest blood test (8/2015), it was 42. I’ve measured my TGs 11 times over the past 10 years-my average value for those measurements is 62. Based on the meta-analysis and centenarian data, that would put me in the lowest risk category for all-cause mortality.

tg mort

If you’re interested, please have a look at my book!

References

Arai Y, Hirose N, Yamamura K, Shimizu K, Takayama M, Ebihara Y, Osono Y. Serum insulin-like growth factor-1 in centenarians: implications of IGF-1 as a rapid turnover protein. J Gerontol A Biol Sci Med Sci. 2001 Feb;56(2):M79-82.

Baranowska B, Bik W, Baranowska-Bik A, Wolinska-Witort E, Szybinska A, Martynska L, Chmielowska M. Neuroendocrine control of metabolic homeostasis in Polish centenarians. J Physiol Pharmacol. 2006 Nov;57 Suppl 6:55-61.

Barbagallo CM, Averna MR, Frada G, Noto D, Cavera G, Notarbartolo A. Lipoprotein profile and high-density lipoproteins: subfractions distribution in centenarians. Gerontology 1998;44(2):106–10.

Bik W, Baranowska-Bik A, Wolinska-Witort E, Kalisz M, Broczek K, Mossakowska M, Baranowska B. Assessment of adiponectin and its isoforms in Polish centenarians. Exp Gerontol. 2013 Apr;48(4):401-7.

Chan YC, Suzuki M, Yamamoto S. Dietary, anthropometric, hematological and biochemical assessment of the nutritional status of centenarians and elderly people in Okinawa, Japan. J Am Coll Nutr. 1997 Jun;16(3):229-35.

Chan YC, Suzuki M, Yamamoto S. A comparison of anthropometry, biochemical variables and plasma amino acids among centenarians, elderly and young subjects. J Am Coll Nutr. 1999 Aug;18(4):358-65.

Liu J, Zeng FF, Liu ZM, Zhang CX, Ling WH, Chen YM. Effects of blood triglycerides on cardiovascular and all-cause mortality: a systematic review and meta-analysis of 61 prospective studies. Lipids Health Dis. 2013 Oct 29;12:159.

Magri F, Muzzoni B, Cravello L, Fioravanti M, Busconi L, Camozzi D, Vignati G, Ferrari E. Thyroid function in physiological aging and in centenarians: possible relationships with some nutritional markers. Metabolism. 2002 Jan;51(1):105-9.

Paolisso G, Ammendola S, Del Buono A, Gambardella A, Riondino M, Tagliamonte MR, Rizzo MR, Carella C, Varricchio M. Serum levels of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 in healthy centenarians: relationship with plasma leptin and lipid concentrations, insulin action, and cognitive function. J Clin Endocrinol Metab. 1997 Jul;82(7):2204-9.

Thillet J, Doucet C, Chapman J, Herbeth B, Cohen D, Faure-Delanef L. Elevated lipoprotein(a) levels and small apo(a) isoforms are compatible with longevity: evidence from a large population of French centenarians. Atherosclerosis 1998;136:389–94.

Vasto S, Scapagnini G, Rizzo C, Monastero R, Marchese A, Caruso C. Mediterranean diet and longevity in Sicily: survey in a Sicani Mountains population. Rejuvenation Res. 2012 Apr;15(2):184-8.

Willcox DC, Willcox BJ, Wang NC, He Q, Rosenbaum M, Suzuki M. Life at the extreme limit: phenotypic characteristics of supercentenarians in Okinawa. J Gerontol A Biol Sci Med Sci. 2008 Nov;63(11):1201-8.

BMI: What’s Optimal For Longevity?

Is there a BMI that is associated with maximally reduced risk of death from all causes? Let’s have a look at the data!

In a meta-analysis of 19 studies that included 1,460,000 adults (median age, 58 years) a BMI between 20-25 kg/m2 was associated with maximally reduced all-cause mortality risk (Berrington de Gonzalez et al. 2010):

both gend nonsmok bmi mort

However, in a meta-analysis of 32 studies that included 197,140 older adults (65 years+), a BMI between 24 and 31 kg/m2 was associated with maximally reduced all-cause mortality risk (Winter et al. 2014). More specifically, a BMI between 26-26.9 kg/m2 was associated with maximally reduced all-cause mortality risk for never-smokers (Winter et al. 2014):

acm 65

So what’s optimal for longevity in terms of BMI, is it 20-25 kg/m2, or potentially higher, as reported in older adults? For additional insight about the association between BMI with all-cause mortality, I looked up the published BMI data for centenarians:

bmi cent

In these 11 studies that included 1075 centenarians, the BMI range was between 19.3-24.4 kg/m2, with an average BMI of 21.8. Shouldn’t that be the BMI reference range for those interested in living past 100?

If you’re interested, please have a look at my book!

References:

Arai Y, Hirose N, Yamamura K, Shimizu K, Takayama M, Ebihara Y, Osono Y. Serum insulin-like growth factor-1 in centenarians: implications of IGF-1 as a rapid turnover protein. J Gerontol A Biol Sci Med Sci. 2001 Feb;56(2):M79-82.

Arai Y, Takayama M, Gondo Y, Inagaki H, Yamamura K, Nakazawa S, Kojima T, Ebihara Y, Shimizu K, Masui Y, Kitagawa K, Takebayashi T, Hirose N. Adipose endocrine function, insulin-like growth factor-1 axis, and exceptional survival beyond 100 years of age. J Gerontol A Biol Sci Med Sci. 2008 Nov;63(11):1209-18.

Baranowska B, Bik W, Baranowska-Bik A, Wolinska-Witort E, Szybinska A, Martynska L, Chmielowska M. Neuroendocrine control of metabolic homeostasis in Polish centenarians. J Physiol Pharmacol. 2006 Nov;57 Suppl 6:55-61.

Barzilai N, Atzmon G, Schechter C, Schaefer EJ, Cupples AL, Lipton R, Cheng S, Shuldiner AR. Unique lipoprotein phenotype and genotype associated with exceptional longevity. JAMA 2003;290:2030–40.

Berrington de Gonzalez A, Hartge P, Cerhan JR, Flint AJ, Hannan L, MacInnis RJ, Moore SC, Tobias GS, Anton-Culver H, Freeman LB, Beeson WL, Clipp SL, English DR, Folsom AR, Freedman DM, Giles G, Hakansson N, Henderson KD, Hoffman-Bolton J, Hoppin JA, Koenig KL, Lee IM, Linet MS, Park Y, Pocobelli G, Schatzkin A, Sesso HD, Weiderpass E, Willcox BJ, Wolk A, Zeleniuch-Jacquotte A, Willett WC, Thun MJ. Body-mass index and mortality among 1.46 million white adults. N Engl J Med. 2010 Dec 2;363(23):2211-9. doi: 10.1056/NEJMoa1000367. Erratum in: N Engl J Med. 2011 Sep 1;365(9):869.

Bik W, Baranowska-Bik A, Wolinska-Witort E, Kalisz M, Broczek K, Mossakowska M, Baranowska B. Assessment of adiponectin and its isoforms in Polish centenarians. Exp Gerontol. 2013 Apr;48(4):401-7.

Chan YC, Suzuki M, Yamamoto S. Dietary, anthropometric, hematological and biochemical assessment of the nutritional status of centenarians and elderly people in Okinawa, Japan. J Am Coll Nutr. 1997 Jun;16(3):229-35.

Hausman DB, Johnson MA, Davey A, Poon LW. Body mass index is associated with dietary patterns and health conditions in georgia centenarians. J Aging Res. 2011;2011:138015.

Magri F, Muzzoni B, Cravello L, Fioravanti M, Busconi L, Camozzi D, Vignati G, Ferrari E. Thyroid function in physiological aging and in centenarians: possible relationships with some nutritional markers. Metabolism. 2002 Jan;51(1):105-9.

Montoliu I, Scherer M, Beguelin F, DaSilva L, Mari D, Salvioli S, Martin FP, Capri M, Bucci L, Ostan R, Garagnani P, Monti D, Biagi E, Brigidi P, Kussmann M, Rezzi S, Franceschi C, Collino S. Serum profiling of healthy aging identifies phospho- and sphingolipid species as markers of human longevity. Aging (Albany NY). 2014 Jan;6(1):9-25.

Paolisso G, Ammendola S, Del Buono A, Gambardella A, Riondino M, Tagliamonte MR, Rizzo MR, Carella C, Varricchio M. Serum levels of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 in healthy centenarians: relationship with plasma leptin and lipid concentrations, insulin action, and cognitive function. J Clin Endocrinol Metab. 1997 Jul;82(7):2204-9.

Vasto S, Scapagnini G, Rizzo C, Monastero R, Marchese A, Caruso C. Mediterranean diet and longevity in Sicily: survey in a Sicani Mountains population. Rejuvenation Res. 2012 Apr;15(2):184-8.

Winter JE, MacInnis RJ, Wattanapenpaiboon N, Nowson CA. BMI and all-cause mortality in older adults: a meta-analysisAm J Clin Nutr. 2014 Apr;99(4):875-90.