Tag Archives: Quantified Self

Michael Lustgarten on Calorie Restricting, Nutrient Tracking, and Blood Testing

Video of my presentation starts at 14:28, and lasts until 1:29:00+!

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

Total Cholesterol: What’s Optimal For Longevity?

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

My albumin values are consistently between 46-48 g/L, but during recent measurements my HDL levels have been lower than optimal (35 mg/dL on 8/2015). The good news is that I was able to increase my HDL from 28 (7/2013 measurement) to 35 mg/dL by adding ~4 oz of fish every day! To further increase my HDL, I’ve doubled my fish oil intake (~3.3 g of combined EPA + DHA per day, from 5-9 g of cod liver oil). I’ll test the effect of this on my circulating biomarkers in a couple of months, so stay tuned!

3/23/2016 Update: Because of concerns that the pre-formed Vitamin A (that is found in cod liver oil) may negate the potential health-promoting effects of optimal Vitamin D levels (Schmutz et al. 2016), I stopped taking cod liver oil during the 3-month period that preceded my latest blood test (3/23/2016). However, I was able to increase my HDL from 35 to 53 mg/dL! I attribute this increase to the daily inclusion of ~60g/walnuts per day. In doing that, although I only replaced ~200 calories from carbohydrates with fat, lower carbohydrate diets have been shown to increase HDL (Manor et al. 2016).

Nonetheless, in terms of the all-cause mortality data that includes total cholesterol (137 mg/dL), albumin (51 g/L), and HDL (53 mg/dL), based on my latest blood test results, my risk is now maximally low!

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 Testing: What’s An Optimal Value For Triglycerides?

In terms of all-cause mortality risk, is the reference range for circulating triglycerides (TG, <150 mg/dL) optimal?

A meta-analysis of 38 studies in 360,556 subjects with a median age of 48y and a 12-year follow-up reported lowest all-cause mortality risk for subjects with TG values less than 90 mg/dL (equivalent to ~1 mmol; Liu et al. (2013)). As shown below, each successive 90 mg/dL increase was associated with a 12% higher all-cause mortality risk. A person with a value closer to the high end of the reference range, ~150 would have a ~7% increased mortality risk compared someone with a value ~90. In other words, there would be 7 more deaths per 100 total people at a TG value of 150, compared with the death rate for people with values less than 90.

tg mortal

Added importance for the association between TG values less than 90 with all-cause mortality risk come from studies of people who have lived longer than 100 years, centenarians. As shown below, triglyceride values less than 101 mg/dL have been reported in 9 of 11 centenarian studies:

tg mort

What’s my TG value? On my latest blood test (8/2015), it was 42. I’ve measured my TGs 11 times over the past 10 years-my average value for those measurements is 62. Based on the meta-analysis and centenarian data, that would put me in the lowest risk category for all-cause mortality.

tg mort

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

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.

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.

Barbagallo CM, Averna MR, Frada G, Noto D, Cavera G, Notarbartolo A. Lipoprotein profile and high-density lipoproteins: subfractions distribution in centenarians. Gerontology 1998;44(2):106–10.

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.

Chan YC, Suzuki M, Yamamoto S. A comparison of anthropometry, biochemical variables and plasma amino acids among centenarians, elderly and young subjects. J Am Coll Nutr. 1999 Aug;18(4):358-65.

Liu J, Zeng FF, Liu ZM, Zhang CX, Ling WH, Chen YM. Effects of blood triglycerides on cardiovascular and all-cause mortality: a systematic review and meta-analysis of 61 prospective studies. Lipids Health Dis. 2013 Oct 29;12:159.

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.

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.

Thillet J, Doucet C, Chapman J, Herbeth B, Cohen D, Faure-Delanef L. Elevated lipoprotein(a) levels and small apo(a) isoforms are compatible with longevity: evidence from a large population of French centenarians. Atherosclerosis 1998;136:389–94.

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.

Willcox DC, Willcox BJ, Wang NC, He Q, Rosenbaum M, Suzuki M. Life at the extreme limit: phenotypic characteristics of supercentenarians in Okinawa. J Gerontol A Biol Sci Med Sci. 2008 Nov;63(11):1201-8.