Monthly Archives: May 2015

Selenium: Dietary Intake And Plasma Values, What’s Optimal For Health?

How much selenium is optimal for health? To address this question, I’ll examine the association between circulating levels of selenium with all-cause mortality risk. Then, I’ll identify a dietary selenium intake that corresponds to optimal plasma selenium levels. Let’s have a look!

A variety of studies have investigated associations between plasma (or serum) selenium with risk of death from all causes:

In a 9-year study of 1,389 older adults (average age, 65y) plasma selenium values less than 1.09 micromolar (uM) were associated with significantly increased all-cause mortality risk, when compared with values greater than 1.22 uM (Akbaraly et al 2005):

se mort2

In a 6-year study of 1,042 older adults (average age, 76y), plasma selenium values less than 0.83 um were associated with significantly increased all-cause mortality risk, when compared with values greater than 1.0 uM (Lauretani et al. 2008):

semort3

In a 5-year study of 632 older women (average age, 74y), serum selenium values less than 1.38 uM were associated with significantly increased all-cause mortality risk, when compared with the other 3 quartiles (1.38 to 1.52, 1.53 to 1.67, and >1.68 uM; Ray et al. 2006):

se mort ray

In a 12-year study of 13,887 middle aged adults (average age, 45y), serum selenium values between 130-150 ng/mL (equivalent to 1.65-1.9 uM) were  associated with reduced all-cause mortality risk (Bleys et al. 2006). Increased mortality risk was associated with serum selenium values less than 1.3 uM (~102 ng/mL):

sel bayes

These data were confirmed in the same cohort (16,008 adults) that were followed for an additional 2 years (14 years total; Goyal  et al. 2013). Baseline serum selenium values greater than 1.4 uM were associated with significantly reduced all-cause mortality risk, compared with values less than1.38 uM.

Finally, in a 13-year study of 1,054 older adults (average age ~76y), elevated plasma levels of selenium (risk ratios were reported without the corresponding selenium concentration) were associated with significantly decreased all-cause mortality risk (Bates et al. 2011).

Studies that show weaker or no association between circulating values of selenium with all-cause mortality risk include Gonzalez et al. (2007) and Wei et al. (2004). In Gonzalez et al. (2007), serum selenium values greater than 1.26 uM were associated with decreased all-cause mortality risk for older women (average age, 76y), but not men, during a 4-year follow-up. However, Gonzalez et al. (2007) may have been underpowered to detect significant associations with mortality risk because of the small study size (215 total subjects). In Wei et al. (2004), a younger cohort (average age, 56y) of 1,115 subjects were followed for 15 years, and no association between serum selenium with all-cause mortality was found. However, only 4% of the population (~46 subjects) had serum selenium values greater than 1.19 uM, a finding that suggests that this study was additionally  under-sized to detect significant associations.

Collectively, these studies suggest that circulating selenium values greater than at least 1.0 uM (and up to ~1.9 uM) are optimal for reducing all-cause mortality risk. What dietary intake of selenium can achieve these circulating values?

Shown below is the correlation between dietary selenium with serum selenium in 205 older adults (average age ~75y; González et al. 2006). Let’s start with the RDA selenium value for adults older than 19 years, 55 micrograms (mcg; Institute of Medicine, 2000). 55 mcg of dietary selenium is correlated with a serum selenium value of ~80 ug/L (~1 uM). In support of this correlation, a dietary selenium intake of ~47 ug/day has been shown to correlate with a circulating selenium concentration of 0.95 uM (Navarro et al. 1995). Based on the evidence already presented, eating only the RDA for selenium and achieving circulating selenium values less 1 uM would be associated with increased risk of death from all causes in 6 of the 7 studies! Based on its association with all-cause mortality risk, the RDA selenium value of 55 mcg/day is too low.

dietary se and ser

Determining which dietary selenium intake is optimal for maximally reduced all-cause mortality risk depends on how you interpret the literature. Four of previously mentioned studies showed circulating selenium values greater than 1.2 uM (95 ug/L) to be associated with reduced all-cause mortality risk. Based on the plot of González et al. (2006), ~130 ug of dietary selenium is necessary to achieve a circulating selenium concentration of 1.2 uM. Three studies showed decreased all-cause mortality risk at circulating selenium levels > 1.38 uM (110 ug/L). The dietary selenium intake that corresponds to that concentration is ~180 ug of selenium/day. Accordingly, a dietary selenium intake between 130-180 ug/day may be optimal for reducing all-cause mortality risk.

Which foods are selenium rich? Brazil nuts are the best dietary source of selenium, as 1 Brazil nut (4 g) contains 77 mcg of selenium (http://ndb.nal.usda.gov/ndb/foods/show/3641?fg=&man=&lfacet=&count=&max=&qlookup=&offset=&sort=&format=Full&reportfmt=other&rptfrm=&ndbno=&nutrient1=&nutrient2=&nutrient3=&subset=&totCount=&measureby=&_action_show=Apply+Changes&Qv=.04&Q6825=1&Q6826=1&Q6827=1). To achieve a dietary selenium intake between 130-180 mcg/day, every day I eat 1 or 2 Brazil nuts. It’s important to note that selenium toxicity can occur at intakes ~400 mcg (Food and Nutrition Board 2000), so keeping an eye on Brazil nut intake is probably a good idea.

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References:

Akbaraly NT, Arnaud J, Hininger-Favier I, Gourlet V, Roussel AM, Berr C. Selenium and mortality in the elderly: results from the EVA study. Clin Chem. 2005 Nov;51(11):2117-23.

Bates CJ, Hamer M, Mishra GD. Redox-modulatory vitamins and minerals that prospectively predict mortality in older British people: the National Diet and Nutrition Survey of people aged 65 years and over. Br J Nutr. 2011 Jan;105(1):123-32.

Bleys J, Navas-Acien A, Guallar E.Serum selenium levels and all-cause, cancer, and cardiovascular mortality among US adults. Arch Intern Med. 2008 Feb 25;168(4):404-10.

Broome CS, McArdle F, Kyle JA, Andrews F, Lowe NM, Hart CA, Arthur JR, Jackson MJ. An increase in selenium intake improves immune function and poliovirus handling inadults with marginal selenium statusAm J Clin Nutr. 2004 Jul;80(1):154-62.

Food and Nutrition Board, Institute of Medicine. Selenium. Dietary reference intakes for vitamin C, vitamin E, selenium, and carotenoids. Washington, D.C.: National Academy Press; 2000:284-324.

González S, Huerta JM, Fernández S, Patterson EM, Lasheras C. Food intake and serum selenium concentration in elderly people.Ann Nutr Metab. 2006;50(2):126-31.

González S, Huerta JM, Fernández S, Patterson AM, Lasheras C. Homocysteine increases the risk of mortality in elderly individuals. Br J Nutr. 2007; 97:1138–1143.

Goyal A, Terry MB, Siegel AB. Serum antioxidant nutrients, vitamin A, and mortality in U.S. adults. Cancer Epidemiol Biomarkers Prev. 2013 Dec;22(12):2202-11.

Hurst R, Armah CN, Dainty JR, Hart DJ, Teucher B, Goldson AJ, Broadley MR, Motley AK, Fairweather-Tait SJ. Establishing optimal selenium status: results of a randomized, double-blind, placebo-controlled trialAm J Clin Nutr. 2010 Apr;91(4):923-31.

Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: National Academy Press, 2000.

Lauretani F, Semba RD, Bandinelli S, Ray AL, Ruggiero C, Cherubini A, Guralnik JM, Ferrucci L. Low plasma selenium concentrations and mortality among older community-dwelling adults: the InCHIANTI Study. Aging Clin Exp Res. 2008 Apr;20(2):153-8.

Navarro M, López H, Ruiz ML, González S, Pérez V, López MC. Determination of selenium in serum by hydride generation atomic absorption spectrometry for calculation of daily dietary intake. Sci Total Environ. 1995 Dec 15;175(3):245-52.

Ray AL, Semba RD, Walston J, Ferrucci L, Cappola AR, Ricks MO, Xue QL, Fried LP. Low serum selenium and total carotenoids predict mortality among older women living in the community: the women’s health and aging studies. J Nutr. 2006 Jan;136(1):172-6.

Swanson CA, Longnecker MP, Veillon C, Howe M, Levander OA, Taylor PR, McAdam PA, Brown CC, Stampfer MJ, Willett WC. Selenium intake, age, gender, and smoking in relation to indices of selenium status of adults residing in a seleniferous area. Am J Clin Nutr. 1990 Nov;52(5):858-62.

Wei WQ, Abnet CC, Qiao YL, Dawsey SM, Dong ZW, Sun XD, Fan JH, Gunter EW, Taylor PR, Mark SD. Prospective study of serum selenium concentrations and esophageal and gastric cardia cancer, heart disease, stroke, and total death. Am J Clin Nutr. 2004 Jan;79(1):80-5.

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?

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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.

Jesse Hahn should not be a starting pitcher!

Billy Beane has great success in finding under-valued talent. However, why is Jesse Hahn being used as a starting pitcher? Shown below are his pitching data, including college, the minors and majors.

hahn

What we see is that Hahn has been a starter for almost his entire career. However, his career high for innings pitched in 8 years was last year, totaling 115 innings. Do the A’s intend to get 150 innings out of Hahn as their #5 starter? That seems to be a best case scenario. Including college, Hahn has averaged 57 innings per year, including missing all of 2011. Take out 2011 and his yearly average is still only 66.3 innings! In a worst case scenario, Hahn may not last the full year. Based on these data, Hahn may be best suited for a relief role.

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Stats via thebaseballcube.com

Eat more green leafy vegetables, reduce mortality risk?

Vitamin K is found in 2 predominant forms, Vitamin K1 (phylloquinone), found almost exclusively in green leafy vegetables, and Vitamin K2 (Menaquinone), found in fermented foods, organ meats, meat, butter and eggs. In the data below (Juanola-Falgarona et al. 2014), we see that Vitamin K1 (phylloquinone) is negatively associated with death from all causes:

all cause mortl phylo

Death from all causes was assessed based on the average value for four groups of Vitamin K1 intake: 171 ug/day = blue line, 276 ug/day =red line, 349 ug/day = green line and 626 ug/day = the yellow line. In the data above, Vitamin K1 values less than 349 ug/day are about the same in terms of all-cause mortality risk. However, those who ate 626 ug/day of Vitamin K1 had about half of the mortality risk compared to the lower K1 intake groups! Interestingly, the RDA for Vitamin K, at 90 ug/day seems to be outdated, based on the data above. Also, Vitamin K2 was not associated with all-cause mortality risk, as shown below:

k2 all cause

Based on the K1 mortality data, 626 ug/day seems like a good goal. However, osteocalcin is a Vitamin K-dependent protein that has been shown to be maximally active in the presence of 1000 ug of Vitamin K1 (Binkley et al. 2002)! Osteocalcin is involved in pathways that decline with aging: insulin secretion and β-cell proliferation in the pancreas, energy expenditure by muscle, insulin sensitivity in adipose tissue, muscle and liver, and increased testosterone production (Karsenty and Ferron 2012). Therefore, getting 1000 ug+ per day of Vitamin K1 may optimize all of these functions and, decrease mortality risk!

What’s the take home from these data? Eat more leafy greens! How much is needed to get 1000 ug  per day? Shown below is a short list of foods rich in Vitamin K and the serving size needed to reach 1000 ug. Approximately 4 ounces of cooked kale or 7 oz. of raw spinach will suffice, and at a low calorie yield. Other foods, like broccoli, brussel sprouts or romaine lettuce would need to be consumed in far greater amounts to reach 1000 ug.

k osteo

What’s my daily K1 intake? Shown below is my 7-day average (7/16/2015 – 7/22/2015) for K intake, derived almost exclusively from plant sources. 1379 ug/day puts me well above the 626 ug/day that was associated with reduced mortality risk, and above the 1000 ug/day needed for maximal osteocalcin activation.

my k intake

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References:

Binkley NC, Krueger DC, Kawahara TN, Engelke JA, Chappell RJ, Suttie JW. A high phylloquinone intake is required to achieve maximal osteocalcin gamma-carboxylation. Am J Clin Nutr. 2002 Nov;76(5):1055-60.

Juanola-Falgarona M, Salas-Salvadó J, Martínez-González MÁ, Corella D, Ostrich R, Ros E, Fitó M, Arós F, Gómez-Gracia E, Fiol M, Lapetra J, Basora J, Lamuela-Raventós RM, Serra-Majem L, Pintó X, Muñoz MÁ, Ruiz-Gutiérrez V, Fernández-Ballart J, Bulló M. Dietary intake of vitamin K is inversely associated with mortality risk. J Nutr. 2014 May;144(5):743-50.

Karsenty G, Ferron M. The contribution of bone to whole-organism physiologyNature. 2012 Jan 18;481(7381):314-20.