Category Archives: quantified self

HDL Update: Age-Related Changes, All-Cause Mortality Risk, And Progress Towards The Optimal Range

In November 2020, I made a HDL video based on a meta-analysis in ~3.4 million subjects that was published in July 2020. In Dec 2020, a larger study (n=15.8 million subjects) was published-those data are presented in the video, and compared against the meta-analysis.

In addition, I’ve tested my HDL 2 more times since November 2020, so how’s my progress for getting it into the optimal range? Also, I attempt to derive clinical significance by identifying correlations for higher HDL with lower Lp(a) and hs-CRP.

Video link: https://www.youtube.com/watch?v=MUuKlpyvZaU

Red Blood Cells Decline During Aging, But Can Be Increased Through Diet

Red blood cells (RBC) are the most abundant cell type in the human body. I’ve tracked my RBC levels in conjunction with diet since 2015, and with the goal of reversing the age-related decline for RBCs, which dietary components have the strongest correlation with RBCs?

https://www.youtube.com/watch?v=3JpyDiNxNeE&feature=youtu.be

Kidney Function Declines During Aging-Can It Be Reversed?

Discussed in the video:

Data for changes in kidney function during aging, kidney function values that are associated with an increased risk of death for all causes

What’s my data for kidney function, 2006 – 2020?

Can diet impact kidney function?

Within my data, which foods are correlated with good kidney function?

How are the individual components of these foods (fiber, protein, omega-3 fatty acids) correlated with kidney function?

My Road to Maximize Lifespan – Monitor Biomarkers To Reverse Aging | Dr. Michael Lustgarten | Parts I – VII

Here’s an interview that I did with Richard at Modern Healthspan, one of the best interviewers in aging!

Part I: Monitoring Biomarkers to Reverse Aging:

Part II, Diet, CR & Fasting:

Part III: Exercise, Protein

Part IV: Optimize Nutrients Through Diet

Part V: Inhibit CD38 to Optimize NAD

Part VI: Microbiome Impact on Muscle Metabolism

Part VII: Preferred Diet & Habit for Longevity

HDL: What’s Optimal For Minimizing Disease Risk And Maximizing Longevity?

Meta-analysis for the association between HDL with all-cause mortality risk has identified HDL levels 55 – 60 mg/dL range as optimal. However, that data includes subjects up to 85y-in the video, I present data for 85y – 115yr olds that additionally suggests HDL in the 55 – 60 mg/dL range as optimal. In addition, I show my own HDL data over the past 15 years (n=34), the correlation for HDL with my diet, and how I plan on consistently increasing my 15-year average HDL of ~44 mg/dL to the 50’s.

Quantifying Biological Age: Blood Test #5 in 2020

My latest blood test results are in-how’s my biological age?

In the video I discuss my dietary approach prior to my latest blood test, the blood test results, and my plan to improve them with diet going forward.

Low Total Cholesterol: Biological Youth Or Increased Mortality Risk?

On my latest blood test (August 2015), my total cholesterol was 127 mg/dL-is that value optimal for health and longevity?

Based on data for 1,104,294 men younger than 60y (median age, 40y) that were followed for up to 14 years (Fulks et al. 2009), my 127 mg/dL value (1 – 2.4%) puts me relatively close to maximally reduced all-cause mortality risk, which occurs at 146-158 mg/dL (5-9% on the graph below):

c hdl mort

But what about the data for men older than 60?

In a 10-year study of 2,277 older adults (average age, ~77y), total cholesterol levels less than 175 mg/dL were associated with ~2-fold higher risk of all-cause mortality, compared with values greater than 226 mg/dL (Schupf et al. 2005):

tc less 175 acm

Similarly, in a 10-year study of even older adults (median age, 89y; 724 subjects), all-cause mortality risk was significantly increased in subjects with total cholesterol values less than 193 mg/dL (dark black line below), compared with values greater than 251 mg/dL (dashed line; Weverling-Rijnsburger et al. 1997). In addition, subjects with cholesterol values greater than 251 mg/dL lived ~2 years longer than those with values less than 191 mg/dL. So higher cholesterol in very old adults…increased lifespan! Does that mean I should alter my dietary approach to increase my circulating cholesterol levels after I reach 60?

chol 89y mort.png

To address that issue, it’s important to understand why cholesterol increases during aging. One possible mechanism involves the role of cholesterol in immune defense against infectious agents (bacteria, viruses, parasites, etc.). Obviously, our immune system is supposed to eliminate these pathogens, but immune function decreases with age (Targonski et al. 2007). As a compensatory mechanism, cholesterol can protect against infectious agents. For example, LDL cholesterol binds to and partially inactivates Staphylococcus aureus (Bhakdi et al. 1983). Staphylococcus aureus infection increases during aging, as its incidence rate is ~3-fold higher in adults older than 60y, when compared with younger subjects (Laupland et al. 2008). In addition, LDL cholesterol inhibits bacterial endotoxin (Weinstock et al. 1992), whose presence in the blood increases during aging (Ghosh et al. 2015). In support of the link between circulating cholesterol with infectious agents, in the older adults of Weverling-Rijnsburger et al. (1997), cholesterol values greater than 251 mg/dL (solid black line) were associated with significantly decreased infectious disease-related mortality, when compared with values less than 193 mg/dL:

infect mort

So if we’re better able to keep infectious agents out of our blood, that would be expected to reduce the need for elevated circulating cholesterol during aging. How can we do that?

One approach involves increased dietary fiber. Fermentation of dietary fiber by gut bacteria produces short-chain fatty acids, which improve gut barrier function (Chen et al. 2013), and decrease cholesterol synthesis (Wright et al. 1990). However, older adults do not eat high-fiber diets, as values of only ~19g/day have been reported (Lustgarten et al. 2014). In contrast, dietary fiber intakes greater than only 29g/day are associated with less infectious disease (and all-cause mortality) risk (Park et al. 2011). So definitely eating at least 29g fiber/day is important, but is that amount optimal to minimize the need for elevated cholesterol during aging?

In a 2-week study of the role of dietary fiber on circulating cholesterol, subjects that ate only 10g fiber/1000 calories did not significantly reduce their baseline total cholesterol values from ~182 mg/dL (Jenkins et al. 2001). In contrast, a dietary fiber intake of 19g/1000 calories reduced baseline total cholesterol from 185 to 150 mg/dL, and subjects that ate even more fiber than that, 55g/1000 calories reduced their total cholesterol values from ~182 to 142 mg/dL, a drop that was also significantly different compared with the 19g fiber/1000 calorie group.

Collectively, these data suggest that to maximally boost gut barrier function, thereby minimizing circulating infectious agents and the need for elevated circulating cholesterol during aging, a very-high fiber-diet may be important. Accordingly, my average daily fiber intake is ~100 g/day on a 2300 calorie diet, resulting in ~43g fiber/1000 calories. Based on this, I don’t expect for my total cholesterol values to change during aging, as my gut barrier function will be optimal, and infectious agents in my blood will be minimized.

To add some specificity to this approach, 2 additional measurements may be important: serum albumin and HDL cholesterol. In agreement with the studies of Weverling-Rijnsburger et al. and Schupf et al., in a 5-year study of 4,128 older adults (average age, ~79y), those with total cholesterol values less than 160 mg/dL had significantly higher all-cause mortality risk, compared with values greater than 240 mg/dL (Volpato et al. 2001):

low tc mortl

However, when considering subjects’ albumin and HDL cholesterol levels, the differential mortality risk was abolished. Subjects that had low total cholesterol but also high (within-range) albumin and HDL had improved survival compared to the higher cholesterol groups:

adj tc mort for alb hdl

If your total cholesterol values are less than 160 mg/dL, what serum albumin and HDL values should you shoot for? As shown below, albumin levels greater than 38 g/L and HDL values greater than 47 mg/dL were associated with maximally reduced all-cause mortality risk in subjects with total cholesterol values less than 160 mg/dL (Volpato et al. 2001):

volpato

8/15/2020: Video update!

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

References

Bhakdi S, Tranum-Jensen J, Utermann G, Füssle R. Binding and partial inactivation of Staphylococcus aureus alpha-toxin by human plasma low density lipoprotein. J Biol Chem. 1983 May 10;258(9):5899-904.

Chen H, Mao X, He J, Yu B, Huang Z, Yu J, Zheng P, Chen D. Dietary fibre affects intestinal mucosal barrier function and regulates intestinal bacteria in weaning piglets. Br J Nutr. 2013 Nov;110(10):1837-48.

Eaton SB, Eaton SB 3rd, Konner MJ. Paleolithic nutrition revisited: A twelve-year retrospective on its nature and implications. Eur J Clin Nutr. 1997 Apr;51(4):207-16.

Fulks M, Stout RL, Dolan VF. Association of cholesterol, LDL, HDL, cholesterol/ HDL and triglyceride with all-cause mortality in life insurance applicants. J Insur Med. 2009;41(4):244-53.

Ghosh S, Lertwattanarak R, Garduño Jde J, Galeana JJ, Li J, Zamarripa F, Lancaster JL, Mohan S, Hussey S, Musi N. Elevated muscle TLR4 expression and metabolic endotoxemia in human agingJ Gerontol A Biol Sci Med Sci. 2015 Feb;70(2):232-46.

Jenkins DJ, Kendall CW, Popovich DG, Vidgen E, Mehling CC, Vuksan V, Ransom TP, Rao AV, Rosenberg-Zand R, Tariq N, Corey P, Jones PJ, Raeini M, Story JA, Furumoto EJ, Illingworth DR, Pappu AS, Connelly PW. Effect of a very-high-fiber vegetable, fruit, and nut diet on serum lipids and colonic function. Metabolism. 2001 Apr;50(4):494-503.

Laupland KBRoss TGregson DBStaphylococcus aureus bloodstream infections: risk factors, outcomes, and the influence of methicillin resistance in Calgary, Canada, 2000-2006. J Infect Dis. 2008 Aug 1;198(3):336-43.

Lustgarten MS, Price LL, Chalé A, Fielding RA. Metabolites related to gut bacterial metabolism, peroxisome proliferator-activated receptor-alpha activation, and insulin sensitivity are associated with physical function in functionally-limited older adults. Aging Cell. 2014 Oct;13(5):918-25.

Mansoor N, Vinknes KJ, Veierød MB, Retterstøl K. Effects of low-carbohydrate diets v. low-fat diets on body weight and cardiovascular risk factors: a meta-analysis of randomised controlled trials. Br J Nutr. 2016 Feb;115(3):466-79.

Park Y, Subar AF, Hollenbeck A, Schatzkin A. Dietary fiber intake and mortality in the NIH-AARP diet and health study. Arch Intern Med. 2011 Jun 27;171(12):1061-8.

Schmutz EA, Zimmermann MB, Rohrmann S. The inverse association between serum 25-hydroxyvitamin D and mortality may be modified by vitamin A status and use of vitamin A supplements. Eur J Nutr. 2016 Feb;55(1):393-402.

Schupf N, Costa R, Luchsinger J, Tang MX, Lee JH, Mayeux R. Relationship Between Plasma Lipids and All-Cause Mortality in Nondemented Elderly. J Am Geriatr Soc. 2005 Feb;53(2):219-26.

Targonski PV, Jacobson RM, Poland GA. Immunosenescence: role and measurement in influenza vaccine response among the elderly. Vaccine. 2007 Apr 20;25(16):3066-9.

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.

Volpato S, Leveille SG, Corti MC, Harris TB, Guralnik JM. The value of serum albumin and high-density lipoprotein cholesterol in defining mortality risk in older persons with low serum cholesterolJ Am Geriatr Soc. 2001 Sep;49(9):1142-7.

Weinstock C, Ullrich H, Hohe R, Berg A, Baumstark MW, Frey I, Northoff H, Flegel WA. Low density lipoproteins inhibit endotoxin activation of monocytes. Arterioscler Thromb. 1992 Mar;12(3):341-7.

Weverling-Rijnsburger AW, Blauw GJ, Lagaay AM, Knook DL, Meinders AE, Westendorp RG. Total cholesterol and risk of mortality in the oldest old. Lancet. 1997 Oct 18;350(9085):1119-23.

Wright RS, Anderson JW, Bridges SR. Propionate inhibits hepatocyte lipid synthesis. Proc Soc Exp Biol Med. 1990 Oct;195(1):26-9.

Blood Test Analysis: 100 – 111y (Centenarians, Semi- and Super-Centenarians)

In order to slow aging, it’s important to know how circulating biomarkers change during aging, and how these biomarkers are associated with risk of death for all causes. In this video, I discuss blood test data for the oldest old, including centenarians (100 – 104y), semi-centenarians (105 – 109y), and super-centenarians (110y+).

 

Biological Age Test #4 in 2020: Getting Better or Getting Worse?

My latest blood test results are in-how’s my biological age? In the video I discuss my dietary approach prior to my latest blood test, the blood test results, and my plan to improve them going forward.

Optimizing Biological Age With Aging.ai: Blood Urea Nitrogen

Blood urea nitrogen (BUN) is one of the 19 variables found on the biological age calculator, aging.ai. It measures the amount of nitrogen, as contained in urea (i.e., blood urea nitrogen, BUN) in your blood. The reference range for BUN is 5 – 20 mg/dL, but within that range, what’s optimal?

First, BUN increases during aging, from 11 – 13 mg/dL in 20 yr olds to 20 – 22 mg/dL in 90 yr olds (Wang et al. 2017):

Screen Shot 2019-11-21 at 5.55.45 AM

The importance of the age-related increase in BUN is illustrated by the finding that risk of death for all causes increases above 15 mg/dL:

BUN

Also note that maximally decreased risk for all cause mortality was associated with BUN values between 5 – 15 mg/dL. In addition, even though a BUN value = 20 mg/dL is technically within the reference range, risk of death for all causes would be 50% higher when compared with someone that had BUN levels between 5 – 15 mg/dL. Collectively, based on the aging and all-cause mortality data, I’d argue that 5 – 13 mg/dL may be the optimal range for BUN.

Assuming normal kidney function (see https://michaellustgarten.wordpress.com/2019/11/18/optimizing-biologic-age-creatinine/), if your BUN is higher than 15 mg/dL, can it be reduced? Note that urea production is almost perfectly correlated (r = 0.98) with dietary protein intake (Young et al. 2000):
urea nitrog

In other words, the main source of dietary nitrogen is protein, so if you eat a lot of protein, you’ll make a lot of urea. Circulating levels of urea can be easily calculated by measuring BUN, via: Urea [mg/dL]= BUN [mg/dL] * 2.14). Therefore, measuring BUN can then be used to determine if your protein intake is too high or too low.

What’s my BUN? As shown below, I’ve measured BUN 22 times since 2015. In line with the Young et al. (2000) data that showed an almost perfectly linear correlation between dietary nitrogen intake with urea production, similarly, as my dietary protein intake has increased, so have my BUN levels. The correlation between my dietary protein intake with BUN is strong (= 0.76, R^2 = 0.575, p-value = 4.3E-05):

upd bun

Note that my BUN is (purposefully) below 15 mg/dL, the upper limit for reduced all-cause mortality risk in Solinger and Rothman (2013), and within the 11 – 13 mg/dL range reported for the 20 yr olds of Wang et al. (2017).

For more recent tracked data, see the video! 

References

Solinger AB, Rothman SI. Risks of mortality associated with common laboratory tests: a novel, simple and meaningful way to set decision limits from data available in the Electronic Medical Record. Clin Chem Lab Med. 2013 Sep;51(9):1803-13.

Wang Z, Li L, Glicksberg BS, Israel A, Dudley JT, Ma’ayan A. Predicting age by mining electronic medical records with deep learning characterizes differences between chronological and physiological ageJ Biomed Inform. 2017 Dec;76:59-68. doi: 10.1016/j.jbi.2017.11.003.

Young VR, El-Khoury AE, Raguso CA, Forslund AH, Hambraeus L. Rates of urea production and hydrolysis and leucine oxidation change linearly over widely varying protein intakes in healthy adults. J Nutr. 2000 Apr;130(4):761-6.

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