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.

Raw Vegan vs. Vegan: Which Diet is Best for Optimal for Health?

In a previous article I wrote about how vegans have been shown to have decreased risk of heart disease, cancer, and all-cause mortality. In addition, in 3 separate articles I’ve written about how cooking food at high temperature (above boiling, 212ºF), whether it is roasting, baking, frying or grilling produces molecules that have been shown to shorten lifespan (AGE products), and, that cause cancer in rodents (both acrylamide and furan). Collectively these data indicate that a vegan diet without cooking any of the food at high temperature is optimal for health. However, within the confines of a vegan diet, which is best for health, raw, or raw plus boiled? In this article, I will discuss why a purely raw food diet is not optimal for health.

In short, the reason is because of fructose. Fructose isn’t only found in HFCS, it’s also the main sugar found in fruit. Raw food diets consist of nuts, seeds, fruit and vegetables. However, on a 80-10-10 diet, in which nuts are rarely used, almost all of the calories will come from fruit. For example, bananas contain 27% fructose (http://ndb.nal.usda.gov/ndb/foods/list). In other words, if you eat nothing but bananas in a single day, this would be equivalent to a 27% fructose diet. And, on the fructose scale, bananas are relatively low in fructose. For example, strawberries, cherries, blueberries, oranges, peaches, pears, grapes, watermelon and apples contain 34%, 35%, 35%, 36%, 40%, 46%, 48%, 53%, 53% fructose, respectively. If you ate nothing but watermelon all day you would be on a 46% fructose diet. So, are there any adverse health effects of this amount of dietary fructose?

The answer is yes: both high and low fructose diets have been shown to elevate blood levels of triglycerides, which are a well documented risk factor for cardiovascular disease (Austin et al. 1998). On a 20% fructose diet for 5 weeks, triglycerides (20%), LDL (12%) and total cholesterol (10%) each increased (Reiser et al. 1989). In contrast, although triglycerides were not found to elevated after 4 weeks of a 20% fructose diet (compared with 3% fructose in the controls) in a separate study, both LDL and total cholesterol were significantly elevated (Swanson et. al  1992). However, evidence from 2 additional studies in humans clearly show the positive association between increased fructose intake and elevated triglycerides. Le et. al (2006) found that fructose supplemented at 1.5g/kg body weight for only 1 month was sufficient to raise blood levels of triglycerides by 36% and VLDL-triglycerides by 72%. The amount of fructose supplemented is the Le study is equivalent to 75g and 105g fructose for a 50kg and 70 kg woman and man, respectively, and can easily be obtained by eating 11-15 bananas. In addition, Faeh et. al (2005) showed that fructose supplemented at 3 grams/kg body weight increased triglycerides by 79%. This amount of supplemented fructose is equivalent to eating 22-30 bananas. In addition, these are relatively low-fructose containing diets.

In contrast, rats fed a 67% fructose diet (the control diet contained only starch) more than doubled plasma triglycerides, increased the concentration of triglycerides in liver, increased liver size, and, decreased liver copper content. The importance of copper depletion is illustrated by its role as a cofactor in the enzyme Copper-Zinc superoxide dismutase (CuZnSOD), the first line of defense against superoxide radicals located in the cytosol of all cells. Depletion of liver copper would be expected to reduce CuZnSOD activity, thereby increasing liver oxidative stress. Indeed, the concentration of lipid peroxidation products was shown to be higher in plasma, heart and urine in rats fed the high fructose diet (Busserolles et al. 2003). The good news is that an all fruit diet would never reach the 67% fructose diet found in the Busserolle study, but evidence from relatively low fructose diets (20%) still show elevations in triglycerides.

If on a raw food diet the answer is to not to eat only fruit, what should be substituted? As mentioned earlier, there is no risk of forming AGE products, acrylamide or furan when boiling food. Therefore, substitution of some amount of fruit on a raw food diet, perhaps one third to half of the total calories should come from whole grains. Boiled whole grains (with vegetables, for the added flavor) is a great way to keep your total fructose intake relatively low. To ensure no loss of nutrients during the boiling process, don’t dump the soup, drink it, it’s delicious! The tocotrienols found almost exclusively in whole grains have been shown to reduce cholesterol (Zaiden et. al 2010), to reduce inflammation (Wu et al. 2008), to reduce DNA damage (Chin et al. 2008), to reduce cancer progression (Wada et al. 2005), and are neuroprotective (Khana et al. 2003). Therefore, when substituting fruit for whole grains, you won’t be sacrificing nutrition!

From a personal experience, in 2011 I switched from a Mediterranean diet to almost exclusively raw vegan. However, my triglycerides, which have never been higher than 60 mg/dL jumped from 40 mg/dL in 2011 to 90 in 2012! Nothing else changed in my routine-the supplements that I take, or how often I exercise, my body weight/composition was the same-only my diet changed. Based on this, it seems like raw plus boiled may be the path to optimal health!

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

References:
Austin MA, Holkanson JE, Edwards KL. Hypertriglyceridemia as a cardiovascular risk factor. Am J Cardiol 1998;81:7B-12B.

Busserolles J, Gueux E, Rock E, Demigné C, Mazur A, Rayssiguier Y. Oligofructose protects against the hypertriglyceridemic and pro-oxidative effects of a high fructose diet in rats.
J Nutr. 2003 Jun;133(6):1903-8.

Chin SF, Hamid NA, Latiff AA, Zakaria Z, Mazlan M, Yusof YA, Karim AA, Ibahim J, Hamid Z, Ngah WZ. Reduction of DNA damage in older healthy adults by Tri E Tocotrienol supplementation. Nutrition. 2008 Jan;24(1):1-10.

Faeh D, Minehira K, Schwarz J, Periasami R, Seongus P, Tappy L. Effect of fructose overfeeding and fish oil administration on hepatic de novo lipogenesis and insulin sensitivity in healthy males. Diabetes 2005;54: 1907-13.

Khanna S, Roy S, Ryu H, Bahadduri P, Swaan PW, Ratan RR, Sen CK. Molecular basis of vitamin E action: tocotrienol modulates 12-lipoxygenase, a key mediator of glutamate-induced neurodegeneration J Biol Chem. 2003 Oct 31;278(44):43508-15.

Lê KA, Faeh D, Stettler R, Ith M, Kreis R, Vermathen P, Boesch C, Ravussin E, Tappy L. A 4-wk high-fructose diet alters lipid metabolism without affecting insulin sensitivity or ectopic lipids in healthy humans. Am J Clin Nutr. 2006 Dec;84(6):1374-9.

Fructose data in foods provided by http://ndb.nal.usda.gov/ndb/foods/list

Reiser S, Powell AS, Scholfield DJ, Panda P, Ellwood KC, Canary JJ. Blood lipids, lipoproteins, apoproteins, and uric acid in men fed diets containing fructose or high-amylose cornstarch. Am J Clin Nutr. 1989 May;49(5):832-9.

Swanson JE, Laine DC, Thomas W, Bantle JP. Metabolic effects of dietary fructose in healthy subjects. Am J Clin Nutr. 1992 Apr;55(4):851-6.

Wada S, Satomi Y, Murakoshi M, Noguchi N, Yoshikawa T, Nishino H. Tumor suppressive effects of tocotrienol in vivo and in vitro. Cancer Lett. 2005;229:181-91.

Wu SJ, Liu PL, Ng LT. Tocotrienol-rich fraction of palm oil exhibits anti-inflammatory property by suppressing the expression of inflammatory mediators in human monocytic cells. Mol Nutr Food Res. 2008 Aug;52(8):921-9.

Zaiden N, Yap WN, Ong S, Xu CH, Teo VH, Chang CP, Zhang XW, Nesaretnam K, Shiba S, Yap YL. Gamma delta tocotrienols reduce hepatic triglyceride synthesis and VLDL secretion. J Atheroscler Thromb. 2010 Oct 27;17(10):1019-32.