Serum Albumin Decreases During Aging: Can Diet Help?

Levels of serum albumin peak at about 20 years old (~4.6 g/dL for males, ~4.4 g/dL for females), then decrease during aging, as shown for the 1,079,193 adults of Weaving et al. (2016):

Screen Shot 2018-07-04 at 1.19.29 PM.png

Similar age-related decreases for serum albumin albumin have also been reported in smaller studies: Gom et al. 2007 (62,854 subjects); Dong et al. 2010 (2,364 subjects); Le Couteur et al. 2010 (1,673 subjects); Dong et al. 2012 (1,489 subjects).

Why is it important that serum levels of albumin decrease during aging? Reduced levels of albumin are associated with an increased risk of death from all causes. For example, in the 1,704,566 adults of Fulks et al. 2010, serum albumin levels > 4.4 g/dL and 4.5 g/dL for females and males, respectively, were associated with maximally reduced risk of death from all causes, regardless of age (younger than 50y, 50-69y, or 70y+):

albumin mort.png

The association between reduced levels of serum albumin with an increased risk of death from all causes have also been found in smaller studies. In a ~9 year study of 7,735 men (age range, 40-59y), when serum albumin was less than 4 g/dL, the mortality rate was 23/1000/per year, compared with 4/1000/per year for subjects with values greater than 4.8 g/dL (Phillips et al. 1989):

albumin 3 mort

Similarly, in older adults (average age, ~80y, 672 subjects), serum albumin levels  greater than 4.5 g/dL (equivalent to 45 g/L) were associated with significantly reduced all-cause mortality risk, when compared with compared with < 4.1 g/dL (equivalent to 41 g/L, Takata et al. 2010):

albumin 2 mort

Decreased levels of serum albumin (less than 4 g/dL) being associated with an increased all-cause mortality risk was also identified in a 12-year study of 287 older adults (average age, ~75y, Sahyoun et al. 1996).

Can the age-related decrease in serum albumin be minimized, or prevented? Shown below is my data for serum albumin since 2005, when I was 32y:

alb

First, note the period from when I was 32y until 40y. No age-related decrease! My average albumin value over 7 measurements was 4.74 g/dL. Unfortunately, I didn’t track my dietary info during that time.

Also note the period from 43y to 45y. First, my albumin levels are significantly higher than the first period, 4.92 g/dL (p=0.027)! Second, again note the absence of an age-related decrease. Based on the data of Weaving et al. (2016), my albumin levels should be around 4.4 g/dL, but I’ve got them going in the opposite direction! How have I been able to do that?

Since April 2015, with use of a food scale, I’ve been tracking my daily dietary intake, including macro and micronutrients (54 variables). For each orange data point in the second period, I have an average dietary intake for each of the 54 variables that I can use to correlate with serum albumin. Based on that data, I can make an educated guess at what could potentially increase, or decrease it.

Of the 54 dietary variables that I track, only 3 were significantly correlated with albumin: positive associations for alpha-carotene (r = 0.66, p = 0.027), beta-carotene (r = 0.75, p =0.007), and a negative association for Vitamin K (r = -0.64, p = 0.03). Shown below is the strongest correlation of the three, beta-carotene, vs. serum albumin.

bcarot alb.png

The majority of my alpha and beta-carotene intake comes from carrots, with a smaller amount coming from butternut squash. Interestingly, beta-cryptoxanthin, a Vitamin A metabolite that is abundant in butternut squash, was not significantly associated with serum albumin. Butternut squash is also a good source of alpha- and beta-carotene, so if  butternut squash was driving the correlation between the carotenes with albumin, I’d expect beta-crypoxanthin to also be significantly associated with it. However, since it’s not, carrots are the most likely source driving the association. Also note that the my average intake of Vitamin K is dramatically higher (1410 mcg; range, 1080-2203 mcg) than the RDA or AI, which are ~100-120 mcg/day. The negative association between my Vitamin K intake with albumin suggests that I should keep it closer to 1100 mcg/day to potentially keep my albumin levels high.

 

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

 

References

Dong MH, Bettencourt R, Barrett-Connor E, Loomba R. Alanine aminotransferase decreases with age: the Rancho Bernardo Study. PLoS One. 2010 Dec 8;5(12):e14254.

Dong MH, Bettencourt R, Brenner DA, Barrett-Connor E, Loomba R. Serum levels of alanine aminotransferase decrease with age in longitudinal analysis. Clin Gastroenterol Hepatol. 2012 Mar;10(3):285-90.e1.

Gom I, Fukushima H, Shiraki M, Miwa Y, Ando T, Takai K, Moriwaki H. Relationship between serum albumin level and aging in community-dwelling self-supported elderly population. J Nutr Sci Vitaminol (Tokyo). 2007 Feb;53(1):37-42.

Dong MH, Bettencourt R, Barrett-Connor E, Loomba R. Alanine aminotransferase decreases with age: the Rancho Bernardo Study. PLoS One. 2010 Dec 8;5(12):e14254.

Fulks M, Stout RL, Dolan VF. Albumin and all-cause mortality risk in insurance applicants. J Insur Med. 2010;42(1):11-7.

Le Couteur DG, Blyth FM, Creasey HM, Handelsman DJ, Naganathan V, Sambrook PN, Seibel MJ, Waite LM, Cumming RG. The association of alanine transaminase with aging, frailty, and mortality. J Gerontol A Biol Sci Med Sci. 2010 Jul;65(7):712-7.

Phillips A, Shaper AG, Whincup PH. Association between serum albumin and mortality from cardiovascular disease, cancer, and other causes. Lancet. 1989 Dec 16;2(8677):1434-6.

Sahyoun NR, Jacques PF, Dallal G, Russell RM. Use of albumin as a predictor of mortality in community dwelling and institutionalized elderly populationsJ Clin Epidemiol. 1996 Sep;49(9):981-8.

Takata Y, Ansai T, Soh I, Awano S, Sonoki K, Akifusa S, Kagiyama S, Hamasaki T, Torisu T, Yoshida A, Nakamichi I, Takehara T. Serum albumin levels as an independent predictor of 4-year mortality in a community-dwelling 80-year-old population. Aging Clin Exp Res. 2010 Feb;22(1):31-5.

Weaving G, Batstone GF, Jones RG. Age and sex variation in serum albumin concentration: an observational study. Ann Clin Biochem. 2016 Jan;53(Pt 1):106-11.

New publications!

Paper #1: Here I propose that the poor muscle composition (muscle that has fat in it) found in older adults may be related to an increased systemic microbial burden:

exp ger.png

https://www.ncbi.nlm.nih.gov/pubmed/29030163

 

Paper #2: In this review, we discuss the emerging gut-muscle axis:

gg ml review.png

https://www.ncbi.nlm.nih.gov/pubmed/29058056

 

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

 

Homocysteine and All-Cause Mortality Risk

On a recent blood test, my plasma level of homocysteine (Hcy) was 11.9 uMol. Is that optimal minimizing disease risk and maximizing longevity? Let’s have a look at the literature.

A 2017 meta-analysis of 11 studies including 27,737 participants showed an increased risk of death from all causes (“all-cause mortality”; ACM) as circulating levels of homocysteine increase (Fan et al. 2017):

hcy acm.png

When looking at meta-analyses, it’s important to examine each of the individual studies. Here are the data for the 11 included studies:

  • Kark et al. 1999: 1,788 older adults, average age 65y, followed for 9-11 years. Compared with values less than 8.5 uMol, subjects with elevated homocysteine (> 14.7) had a 2-fold higher risk of death from all causes.
  • Bostom et al. 1999: 1,933older adults, verage age, 70y, median follow-up, 10y. Subjects with values > 14.3 uMol had 2-fold ACM risk, when compared with < 14.3.
  • Hoogeveen et al. 2000: 811 older adults (average age, 65y), 5 yr follow-up. Non- diabetics had a 34% increased ACM risk (p=0.08), but diabetics had 2.5-fold increased ACM risk after a 5-yr follow-up.
  • Vollset et al. 2001: 4,766 older adults (age range, 65-67y at study entry), median 4 yr follow-up. Compared with 5.1-8.9 uMol, values greater than 12 were significantly associated with a 2.4-4.5 increased ACM risk.
  • Acevedo et al. 2003. 3,427 subjects, average age 56y, ~3yr follow-up. ACM risk lowest for < 9.4 uMol, compared with > 14.4.
  • González et al. 2007: 215 older adults (average age, 75y), median 4 yr follow-up. Compared with < 8.7 uMol, values > 16.7 had 2.3-fold increased ACM risk.
  • Dangour et al. 2008: 853 older adults (average age, 79y), ~7.6y follow-up. Homocysteins > 19.4 uMol associated with ~2-fold higher ACM risk, when compared with < 9.8.
  • Xiu et al. 2012: 1,412 older adults (average age, ~75y), up to 10 year follow-up. 1.8-fold higher ACM risk comparing those with >14.5 uMol with < 9.3.
  • Waśkiewicz et al. 2012: 7,165 middle aged adults, ~5yr follow- up. 1.8-fold increased ACM risk for subjects with homocysteine > 10.5 uMol(average age, 52y) when compared with < 8.2 (avg age, 40y).
  • Wong et al. 2013: 4,248 older men, average age ~77y, ~5yr follow-up. 1.5-fold increased ACM risk for homocysteine values > 15 uMol.
  • Swart et al. 2012: 1,117 older adults (average age, 75y), up to a 7yr follow-up. In 543 men, homocysteine was not associated with ACM risk. In 574 women, 1.7 to 1.9-fold higher ACM risk when comparing  > 12.7 and >15.6 vs < 10.3 uMol.

Not included in their analysis:

  • Petersen et al. 2016: 670 subjects, average age 65y, average follow-up 14.5y. Subjects with homocysteine values ≥ 10.8 μmol/l  had a significant higher incidence of all-cause mortality:

hcy 2

In sum, the evidence appears consistent across these 12 studies that elevated homocysteine is associated with an increased risk of death from all causes. Based on the Fan et al. (2016) meta-analysis, lower appears better, with values < 5 uMol associated with maximally reduced ACM risk. Also based on that data, my ACM risk is ~1.5-fold increased!

To see how dietary changes and supplements have impacted my homocysteine levels, see this link: https://michaellustgarten.com/2018/03/23/reducing-homocysteine-updates/

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

 

References:

Bostom AG, Silbershatz H, Rosenberg IH, Selhub J, D’Agostino RB, Wolf PA, Jacques PF, Wilson PW. Nonfasting plasma total homocysteine levels and all-cause and cardiovascular disease mortality in elderly Framingham men and women. Arch Intern Med. 1999 May 24;159(10):1077-80.

Dangour AD, Breeze E, Clarke R, Shetty PS, Uauy R, Fletcher AE. Plasma homocysteine, but not folate or vitamin B-12, predicts mortalityin older people in the United Kingdom. J Nutr. 2008 Jun;138(6):1121-8.

Fan R, Zhang A, Zhong F. Association between Homocysteine Levels and All-cause Mortality: A Dose-Response Meta-Analysis of Prospective Studies. Sci Rep. 2017 Jul 6;7(1):4769.

González S, Huerta JM, Fernández S, Patterson AM, Lasheras C. Homocysteine increases the risk of mortality in elderly individuals. Br J Nutr. 2007 Jun;97(6):1138-43.

Hoogeveen EK, Kostense PJ, Jakobs C, Dekker JM, Nijpels G, Heine RJ, Bouter LM, Stehouwer CD. Hyperhomocysteinemia increases risk of death, especially in type 2 diabetes : 5-year follow-up of the Hoorn Study. Circulation. 2000 Apr 4;101(13):1506-11.

Kark JD, Selhub J, Adler B, Gofin J, Abramson JH, Friedman G, Rosenberg IH. Nonfasting plasma total homocysteine level and mortality in middle-aged and elderly men and women in Jerusalem. Ann Intern Med. 1999 Sep 7;131(5):321-30.

Petersen JF, Larsen BS, Sabbah M, Nielsen OW, Kumarathurai P, Sajadieh A. Long-term prognostic significance of homocysteine in middle-aged and elderly. Biomarkers. 2016 Sep;21(6):490-6.

Swart KM, van Schoor NM, Blom HJ, Smulders YM, Lips P. Homocysteine and the risk of nursing home admission and mortality in older persons. Eur J Clin Nutr. 2012 Feb;66(2):188-95.

Waśkiewicz A, Sygnowska E, Broda G. Homocysteine concentration and the risk of death in the adult Polish population. Kardiol Pol. 2012;70(9):897-902.

Wong YY, Almeida OP, McCaul KA, Yeap BB, Hankey GJ, Flicker L. Homocysteine, frailty, and all-cause mortality in older men: the health in men study. J Gerontol A Biol Sci Med Sci. 2013 May;68(5):590-8.

Vollset SE, Refsum H, Tverdal A, Nygård O, Nordrehaug JE, Tell GS, Ueland PM. Plasma total homocysteine and cardiovascular and noncardiovascular mortality: the Hordaland Homocysteine Study. Am J Clin Nutr. 2001 Jul;74(1):130-6.

 

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.