Tag Archives: Mortality Risk

Ergothioneine: A ‘Longevity Vitamin’ With Potential Benefits For Age-Related Outcomes?

Papers referenced in the video:

Dietary Thiols: A Potential Supporting Strategy against Oxidative Stress in Heart Failure and Muscular Damage during Sports Activity: https://www.ncbi.nlm.nih.gov/pmc/arti…

Ergothioneine levels in an elderly population decrease with age and incidence of cognitive decline; a risk factor for neurodegeneration? https://pubmed.ncbi.nlm.nih.gov/27444…

Is ergothioneine a ‘longevity vitamin’ limited in the American diet? https://www.ncbi.nlm.nih.gov/pmc/arti…

Frailty markers comprise blood metabolites involved in antioxidation, cognition, and mobility: https://pubmed.ncbi.nlm.nih.gov/32295…

Ergothioneine is associated with reduced mortality and decreased risk of cardiovascular disease: https://pubmed.ncbi.nlm.nih.gov/31672…

Ergothioneine – a diet‐derived antioxidant with therapeutic potential: https://febs.onlinelibrary.wiley.com/…

Ergothioneine, a metabolite of the gut bacterium Lactobacillus reuteri, protects against stress-induced sleep disturbances: https://www.nature.com/articles/s4139…

Neutrophils, Lymphocytes, Monocytes: What’s Optimal For Health And Longevity?

White blood cells (WBCs) comprise many different cell types, including neutrophils, lymphocytes, monocytes, eosinophils, and basophils.

Neutrophils, lymphocytes, and monocytes account for ~99% of WBCs, and accordingly, in the video I propose optimal ranges for these cell types in terms of health and longevity.

Longevity Genes: APOE

A reduced mortality risk and an increased lifespan has been reported for people who have APOE2 alleles, when compared with APOE3 or APOE4, but beyond associations, data for lifespan in APOE-expressing mice was recently reported, evidence that supports a causative role for APOE on longevity.

Resting Heart Rate And Heart Rate Variability: What’s Optimal?

To determine what’s optimal for resting heart rate and heart rate variability, I review the published literature for how they change during aging, and what’s associated with mortality risk. Also included are my data over the past ~2 years, to see how I compare against the literature.

Vitamin K1 (Phylloquinone): How Much Is Optimal For Health?

An adequate daily intake of Vitamin K1 is 120 and 90 micrograms/day for males and females, respectively, but are those amounts optimal for health? In this video, I present evidence that consuming more than 1000 micrograms of Vitamin K1/day may be optimal.

Green Tea and Mortality Risk, Update!

In an earlier post (https://michaellustgarten.wordpress.com/2019/09/15/drink-green-tea-reduce-and-all-cause-mortality-risk/), I reported that green tea consumption is associated with reduced risk of death for all causes. Now, there’s more recent data! Drinking more than 1 cup of green tea per day is associated with reduced all-cause mortality risk in a pooled analysis of 8 studies that included 313,381 subjects (age range, 40-103y; Abe et al. 2019).

In women (168,631 subjects), risk of death for all causes was reduced by 10%, 6%, and 18% for 1-2, 3-4, and greater than 5 cups/day, when compared with drinking less than 1 cup per day:

gt wom

In men (144,750 subjects), risk of death for all causes was reduced by 5%, 7%, and 10% for 1-2, 3-4, and greater than 5 cups/day, when compared with drinking less than 1 cup per day:

gtea men.png

Cheers to green tea, for health!

Reference

Abe SK, Saito E, Sawada N, Tsugane S, Ito H, Lin Y, Tamakoshi A, Sado J, Kitamura Y, Sugawara Y, Tsuji I, Nagata C, Sadakane A, Shimazu T, Mizoue T, Matsuo K, Naito M, Tanaka K, Inoue M; Research Group for the Development and Evaluation of Cancer Prevention Strategies in Japan. Green tea consumption and mortality in Japanese men and women: a pooled analysis of eight population-based cohort studies in Japan. Eur J Epidemiol. 2019 Oct;34(10):917-926. doi: 10.1007/s10654-019-00545-y.

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

Optimizing Biological Age: MCV

Mean corpuscular volume (MCV) is one of the 10 variables included in the biological age calculator, PhenoAge (see https://michaellustgarten.wordpress.com/2019/09/09/quantifying-biological-age/). It’s calculated by dividing the fraction of the blood that contains RBCs (hematocrit) by RBCs (MCV = hematocrit/RBC), thereby identifying the average volume contained within red blood cells. Although the MCV reference range is 80 – 100 femtoliters (10^-15L), what’s optimal in terms of a youthful biological age, and minimized disease risk?

MCV increases during aging. In support of this, using a small subset of samples from the Baltimore Longitudinal Study on Aging (values not in parentheses), MCV increased from average values of 88.8 in young (18-39y), to 91.3 in middle-aged (40-59y), to 92.4 in old (>60y) subjects. Similarly, MCV also increased in the full sample size from the Baltimore Longitudinal Study on Aging (values in parentheses) from 89.2 to 91.1 to 92.9 in young, middle-aged and old, respectively (Araki and Rifkind, 1984):

Screen Shot 2019-10-12 at 3.32.31 PM

In a larger study that included 3,358 subjects, MCV increased from median values of 92.2 in women and 93.4 in men younger than 60y to 94.2 and 95.7 in women and men older than 60y, respectively (Lee et al. 2018):

mcv age

When considering that MCV increases during aging, one would predict that higher levels would be associated with an increased risk of death of all causes. In support of this, in the 36,260 subjects of Yoon et al. (2016), MCV levels > 94.2 in women and > 95.8 in men (Tertile 4) were associated with a 55% and 44% increased risk of death from all causes, respectively, when compared with MCV values between 89.2 – 91.6 in women and 90.5 – 93 in men (Tertile 2):

mcv acm

Collectively, these data suggest that a lower MCV may be better in terms of biologic youth,  and for a lower risk of death from all causes. What are my MCV values? I’ve measured MCV 25 times over the past 16 years. In my 30’s, I measured it 7 times, with an average MCV = 90. In my 40’s, I’ve measured it 18 times, for an average value = 91.1. Although these 2 groups of data are not significantly different (p=0.09), the red trendline for these data is slightly up (R2=0.02), which suggests that my MCV is slowly increasing with age:

mcv me

Although my MCV values are seemingly far from the increased mortality risk of Yoon et al. (> 95.8), it increases during aging, so I’ve definitely got my eye on it. Should it start to increase, I’ll intervene with dietary changes. Stay tuned!

 

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

 

References

Araki K, Rifkind JM. Age dependent changes in osmotic hemolysis of human erythrocytes. J Gerontol. 1980 Jul;35(4):499-505.

Lee Eun-jin, Kim Mi-young, Lee Eun-yeop, Jeon Beom, Lee Ji-won, Kim Han-sung, Kang Hee-jeong, Lee Young-kyung, Eun Jin Lee, Miyoung Kim, Eunyup Lee, Kibum Jeon, Jiwon Lee, Han-Sung Kim, Hee Jung Kang, Young Kyung Lee.vEstablishment of reference section for general blood test in healthy elderly. Establishing Reference Intervals for Complete Blood Cell Count in Healthy Korean Elderly Individuals. J Lab Med Qual Assur 2018; 40: 27-37. doi.org/10.15263/jlmqa.2018.40.1.27.

Yoon HJ, Kim K, Nam YS, Yun JM, Park M. Mean corpuscular volume levels and all-cause and liver cancer mortality. Clin Chem Lab Med. 2016 Jul 1;54(7):1247-57. doi: 10.1515/cclm-2015-0786.

Optimizing Biological Age: Alkaline Phosphatase

Alkaline phosphatase (ALP) is one of the 10 variables used to quantify biological age with PhenoAge (https://michaellustgarten.wordpress.com/2019/09/09/quantifying-biological-age). The reference range for alkaline phosphatase is 20 – 140 IU/L*, but within that range, what’s optimal?

Two separate meta-analyses have investigated the association between serum levels of ALP with risk of death for all causes. First, in a meta-analysis of 4 studies that included ~9 million adults, ALP values greater than 48 IU/L were associated with a significantly increased all-cause mortality risk (Kunutsor et al. 2014):

Screen Shot 2019-10-06 at 1.30.37 PM

In another meta-analysis that included 24 studies and 147,634 subjects (Li et al. 2014), lowest risk of death for all causes was identified for ALP values ~50 IU/L:

Screen Shot 2019-10-05 at 8.00.38 AM

Note that mortality risk increased linearly up to 85 U/L (short dashed line, dark black line), but increased at a much greater rate for values greater than 85 U/L. In addition, the meta-analysis of Li et al. 2014 did not include the 8.9 million adults of Fulks et al. (2008), which were included in the Kunutsor meta-analysis. Nonetheless, the data from these 2 complimentary meta-analyses arrive at the same conclusion: lower ALP values may be better in terms of reducing risk of death from all causes.

Investigating further, ALP levels increase during aging from ~60-80 U/L in adults < 55y to > 80 U/L in adults > 55y (Strømme et al. 2005, Han et al. 2016), evidence that further suggests that lower may be better:

Screen Shot 2019-10-06 at 12.36.55 PM

What are my ALP values? As shown below, I’ve measured ALP 27 times over the past 13 years, with an average value of 49.4 U/L (black line). Also note the red dotted trend line, which is close to flat over that period. So far, so good for ALP!

alp

*Note that IU/L = U/L

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

References

Fulks M, Stout RL, Dolan VF. Using liver enzymes as screening tests to predict mortality risk. J Insur Med 2008;40:191–203.

Han L, Wang J, Zhang Q, Ke P, Wu X, Wan Z, Lin H, Zeng R, Huang X, Zhuang J. Development of reference intervals for serum alkaline phosphatase among adults in Southern China traced to the new IFCC reference measurement procedure. Clin Chem Lab Med. 2016 Apr;54(4):659-65. doi: 10.1515/cclm-2015-0732.

Kunutsor SK, Apekey TA, Seddoh D, Walley J. Liver enzymes and risk of all-cause mortality in general populations: a systematic review and meta-analysis. Int J Epidemiol. 2014 Feb;43(1):187-201.

Li JW, Xu C, Fan Y, Wang Y, Xiao YB. Can serum levels of alkaline phosphatase and phosphate predict cardiovascular diseases and total mortality in individuals with preserved renal function? A systemic review and meta-analysisPLoS One. 2014 Jul 17;9(7):e102276.

Strømme JH, Rustad P, Steensland H, Theodorsen L, Urdal P. Reference intervals for eight enzymes in blood of adult females and males measured in accordance with the International Federation of Clinical Chemistry reference system at 37 degrees C: part of the Nordic Reference Interval Project. Scand J Clin Lab Invest. 2004;64(4):371-84. Erratum in: Scand J Clin Lab Invest. 2005;65(1):83-4.

Optimizing Biological Age: RDW%

Can biological age be optimized? The red blood cell (RBC) distribution width (RDW%) is one of the variables included in the PhenoAge biological age calculator (see https://michaellustgarten.wordpress.com/2019/09/09/quantifying-biological-age/). Although the RDW% reference range is 11.5% – 14.5%, what values are optimal in terms a youthful biological age, and minimized disease risk?

First, let’s define RDW%. RDW% is calculated by dividing the standard deviation of the average mean corpuscular volume (i.e. the average volume inside red blood cells, defined as MCV, upper right panel; image via Danese et al. 2015). When the volume inside red blood cells is approximately the same across all RBCs (upper left panel), the RDW% will be narrow, as shown by the dashed line in the upper right panel.  Conversely, during aging and in many diseases, the size and volume of RBCs are altered, resulting in a more broad RDW% (bottom left and right panels):

ani

In terms of RDW%, what’s optimal for health and longevity? In the the largest study  (3,156,863 subjects) that investigated the association for risk of death for all causes with RDW%, maximally reduced risk of death was observed for RDW% between 11.4 – 12.5% (percentiles 1-5, 5-25), with mortality risk increasing for values < 11.3%, and > 12.6% (Tonelli et al. 2019):

rdw 2

This has been confirmed in other relatively large studies (240,477 subjects), as RDW% values < 12.5% were associated with maximally reduced all-cause mortality risk, with values > 12.5 associated with an increasing all-cause mortality risk (Pilling et al. 2018):

rdw 3

How does RDW% change during aging? For the 1,907 subjects of Lippi et al. (2014), RDW% increased during aging:

rdw 4

In support of this finding, RDW% also increased during aging in a larger study that included 8,089 subjects (Hoffmann et al. 2015).

Collectively, when considering the all-cause mortality and aging data, RDW% values ~ 12.5% may be optimal for health and longevity. What are my RDW% values? Plotted below are 18 RDW% measurements since 2015 (blue circles). First, note my average RDW% during that time (black line) is 12.8%, which isn’t far from the 12.5% that may be optimal for health and longevity. However, note the trend line (red), which indicates that my RDW% values are increasing during aging!

rdw 5

How do I plan on reducing my RDW%? A moderate strength correlation exists between my calorie intake with RDW% (r = 0.53), with a higher daily average calorie intake being associated with a higher RDW%:
my rdw
My plan is to shoot for a daily calorie intake ~2600 over the next month, and then retest my RDW% (and the rest of the CBC). Hopefully that brings my RDW% down to 12.5% or less. If that doesn’t work, I’ll re-calibrate, and try something else!

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

References

Danese E, Lippi G, Montagnana M. Red blood cell distribution width and cardiovascular diseasesJ Thorac Dis. 2015 Oct;7(10):E402-11. doi: 10.3978/j.issn.2072-1439.2015.10.04.

Hoffmann JJ, Nabbe KC, van den Broek NM. Red cell distribution width and mortality in older adults: a meta-analysis. Clin Chem Lab Med. 2015 Nov;53(12):2015-9. doi: 10.1515/cclm-2015-0155.

Lippi G, Salvagno GL, Guidi GC. Red blood cell distribution width is significantly associated with aging and gender. Clin Chem Lab Med. 2014 Sep;52(9):e197-9. doi: 10.1515/cclm-2014-0353.

Pilling LC, Atkins JL, Kuchel GA, Ferrucci L, Melzer D. Red cell distribution width and common disease onsets in 240,477 healthy volunteers followed for up to 9 years. PLoS One. 2018 Sep 13;13(9):e0203504. doi: 10.1371/journal.pone.0203504.

Tonelli M, Wiebe N, James MT, Naugler C, Manns BJ, Klarenbach SW, Hemmelgarn BR. Red cell distribution width associations with clinical outcomes: A population-based cohort studyPLoS One. 2019 Mar 13;14(3):e0212374. doi: 10.1371/journal.pone.0212374.