6 replies to this topic

[Shepard]

Thanks to Stephen Coles of the GRG:

Multivitamin use and telomere length in women1,2,3
Qun Xu, Christine G Parks, Lisa A DeRoo, Richard M Cawthon, Dale P Sandler and Honglei Chen

1 From the Epidemiology Branch, National Institute for Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (QX, CGP, LAD, DPS, and HC), and the Department of Human Genetics, University of Utah, Salt Lake City, UT (RMC).

2 Supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01ES044005 AND Z01ES101986), and the Department of Defense Breast Cancer Research Concept Award (BC045286).

3 Address reprint requests and correspondence to H Chen, Epidemiology Branch, National Institute of Environmental Health Sciences, 111 TW Alexander Drive, PO Box 12233, Mail drop A3-05, Research Triangle Park, NC 27709. E-mail chenh2@niehs.nih.gov.

ABSTRACT

Background: Telomere length may be a marker of biological aging. Multivitamin supplements represent a major source of micronutrients, which may affect telomere length by modulating oxidative stress and chronic inflammation.

Objective: The objective was to examine whether multivitamin use is associated with longer telomeres in women.

Design: Cross-sectional analysis of data from 586 early participants (age 35–74 y) in the Sister Study. Multivitamin use and nutrient intakes were assessed with a 146-item food-frequency questionnaire, and relative telomere length of leukocyte DNA was measured by quantitative polymerase chain reaction.

Results: After age and other potential confounders were adjusted for, multivitamin use was associated with longer telomeres. Compared with nonusers, the relative telomere length of leukocyte DNA was on average 5.1% longer among daily multivitamin users (P for trend = 0.002). In the analysis of micronutrients, higher intakes of vitamins C and E from foods were each associated with longer telomeres, even after adjustment for multivitamin use. Furthermore, intakes of both nutrients were associated with telomere length among women who did not take multivitamins.

Conclusion: This study provides the first epidemiologic evidence that multivitamin use is associated with longer telomere length among women.

Received for publication September 18, 2008. Accepted for publication February 8, 2009.

Oh, snap. Let the arguments begin anew.

What's that old saying about correlation and causation?

[niner]

Oh, snap. Let the arguments begin anew.

What's that old saying about correlation and causation?

Well, they adjusted for "age and other potential confounders"...

So here's another way to keep your telomeres longer.

Biochem Biophys Res Commun. 2004 Nov 12;324(2):931-6.
L-carnosine reduces telomere damage and shortening rate in cultured normal fibroblasts.
Shao L, Li QH, Tan Z.
Institute of Zoology, Chinese Academy of Sciences, Beijing 100080, PR China.
Telomere is the repetitive DNA sequence at the end of chromosomes, which shortens progressively with cell division and limits the replicative potential of normal human somatic cells. L-carnosine, a naturally occurring dipeptide, has been reported to delay the replicative senescence, and extend the lifespan of cultured human diploid fibroblasts. In this work, we studied the effect of carnosine on the telomeric DNA of cultured human fetal lung fibroblast cells. Cells continuously grown in 20 mM carnosine exhibited a slower telomere shortening rate and extended lifespan in population doublings. When kept in a long-term nonproliferating state, they accumulated much less damages in the telomeric DNA when cultured in the presence of carnosine. We suggest that the reduction in telomere shortening rate and damages in telomeric DNA made an important contribution to the life-extension effect of carnosine.
PMID: 15474517

Note: 20mM is a lot.

[solarfingers]

I know I'm resurrecting an old thread but it was sent to me by Logic. I find it interesting that Carnosine had a positive effect in reducing telomere shortening in protecting DNA.

[niner]

Someone should slap me upside the head for posting a misleading in vitro paper. In my defense, I did mention that 20mM was a lot, but that post is still an embarrassment. It was only four years ago, I should have known better. Sorry. The problem with it is that it is entirely irrelevant to the real world. I doubt you could hit 20 mM ever with normal carnosine doses taken orally. Maybe with a continuous IV and high doses...

I happened to run across this paper which shows that carnosine is at least temporarily bioavailable in humans:

J Agric Food Chem. 2005 Jun 15;53(12):4736-9.
Quantitation of carnosine in humans plasma after dietary consumption of beef.
Park YJ, Volpe SL, Decker EA.

Department of Food Science, Chenoweth Lab, University of Massachusetts, Amherst, Massachusetts 01003, USA.

Carnosine (beta-alanyl-L-histidine) is a dipeptide found in the muscle foods that has been postulated to be a bioactive food component. The objective of this research was to determine the concentration of carnosine in human plasma after ingestion of beef. Nine males and nine females were recruited for the study. Food devoid of meat products was given to the subjects so that they did not consume carnosine for 48 h prior to the test. Subjects fasted for 12 h and then had blood withdrawn prior to a meal containing 200 g of ground beef. Additional blood samples were collected over the following 24 h and carnosine concentrations were determined by HPLC. The cooked ground beef used in the study contained 52% water, 24% protein, 22% fat, and 124 mg of carnosine/100 g of beef. No plasma carnosine was detected in subjects before the consumption of the beef. Carnosine was detected in plasma 15 min after beef consumption. Plasma carnosine concentrations continued to increase with a maximum (32.7 mg of carnosine/L of plasma) being recorded 2.5 h after consumption. Carnosine concentrations then decreased until no carnosine could be detected at 5.5 h postconsumption. These results indicate that dietary carnosine is absorbed into human plasma after the consumption of beef. Since carnosine has several potential health benefits, evidence of its bioavailability suggests that it could be a bioactive food component.

PMID: 15941308

These subjects got 248mg carnosine in ground beef. The Cmax (at Tmax = 2.5 hours) was 32.7mg/L. Multiplying by (1mmole/226mg) gives 0.16 mM, so the cells in in vitro paper were soaked in a concentration 125 times as high. In this experiment, the concentration of carnosine had fallen to zero in 5.5 hours. If you took a gram of pure carnosine, you would hit Cmax a lot faster, but it would probably clear more quickly as well. The Cmax would probably be more than 4 times higher, but you would need even more (a lot more, for a lot longer) to have the effect on telomeres noted in the in vitro paper. This human PK study at least gives me hope that dosing near a meal might provide some AGE protection in the post-prandial period when glucose is highest. There's still the question of what concentration of carnosine is needed to protect against AGEs effectively.

[niner]

This human PK study at least gives me hope that dosing near a meal might provide some AGE protection in the post-prandial period when glucose is highest.

Maybe, or maybe not, according to this contradictory work:

Amino Acids. 2010 Mar;38(3):847-58. doi: 10.1007/s00726-009-0291-2. Epub 2009 Apr 19.
Profiling histidine dipeptides in plasma and urine after ingesting beef, chicken or chicken broth in humans.
Yeum KJ, Orioli M, Regazzoni L, Carini M, Rasmussen H, Russell RM, Aldini G.

Jean Mayer USDA, Human Nutrition Research Center on Aging, Tufts University, 711 Washington St., Boston, MA 02111, USA. kyungjin.yeum@tufts.edu

The in vitro metabolic stability of histidine-dipeptides (HD), carnosine (CAR) and anserine (ANS), in human serum, and their absorption kinetics after ingesting pure carnosine or HD rich foods in humans have been investigated. Healthy women (n = 4) went through four phases of taking one dose of either 450 mg of pure carnosine, 150 g beef (B), 150 g chicken ©, or chicken broth (CB) from 150 g chicken with a >2-week washout period between each phase. Blood samples were collected at 0, 30, 60, 100, 180, 240, and 300 min, and urine samples before and after (up to 7 h) ingesting pure carnosine or food. Both plasma and urine samples were analyzed for HD concentrations using a sensitive and selective LC-ESI-MS/MS method. CAR was undetectable in plasma after ingesting pure carnosine, B, C or CB. By contrast, plasma ANS concentration was significantly increased (P < 0.05) after ingesting C or CB, respectively. Urinary concentrations of both CAR and ANS were 13- to 14-fold increased after ingesting B, and 14.8- and 243-fold after CB ingestion, respectively. Thus, dietary HD, which are rapidly hydrolyzed by carnosinase in plasma, and excreted in urine, may act as reactive carbonyl species sequestering agents.

PMID: 19381778

So this group finds NO carnosine in plasma, either from pure carnosine or meat. They do detect Anserine, and go on to say "Thus, dietary HD, which are rapidly hydrolyzed by carnosinase in plasma, and excreted in urine, may act as reactive carbonyl species sequestering agents."

That doesn't make much sense, unless they're saying that Anserine could sequester reactive carbonyls. Can anyone get access to the full text of this paper?

[solarfingers]

Niner, I just thought it was interesting. I know that bio-availability is a concern. I have heard others who say they are seeing good results from using L-Carnosine. From my experience it seems to be doing more visibly than anything I have ever tried before. Understand that vanity is not my trademark yet I do believe if something is going well with my skin then there is a good chance that something is going on inside that is advantageous. I started taking just 1000mg a day and after the first week started taking L-Carnosine 2000mg , Taurine 500mg and L-Histinine 500mg a day for the last three weeks. Here are some before and after pics of my arm.



In the before pic there is visible signs of thinning and you can tell that gravity is pulling the skin downward. This pic was taken in May 2013.



This pic was taken today 2 July 2013. What I hope it demonstrates is the appearance of elasticity. If you notice in the earlier pic the skin appears to be a bit more thinner looking. You can especially see it toward the top of the arm. You can also see that gravity seems to be pulling the skin a bit and it looks to be drooping ever so slightly. The color may look better in the second photo but even though I tried to get the photo exactly the same it seems to be a little lighter in the later photo. Perhaps the skin color is better but I can't tell from then to now. I just know that the nature of the skin is more supple and elastic and I have lost that orange peal look I once had.

[hav]

Don't know if you consider that NAC fits the category... its an antioxidant derivative of the amino acid L-cysteine. Its been shown that longer telomeres are found in the ovaries of older mice that take it:

Delay in oocyte aging in mice by the antioxidant N-acetyl-L-cysteine (NAC)

Short-term treatment of mice for 2 months with NAC demonstrated that NAC improved the quality of fertilized oocytes and early embryo development. Mice treated with a long-term low concentration (0.1 mM) of NAC had increased litter sizes at the ages of 7-10 months compared with age-matched controls without NAC treatment. NAC also increased the quality of the oocytes from these older mice. Moreover, the expression of sirtuins was increased, telomerase activity was higher and telomere length was longer in the ovaries of mice treated with NAC compared with those of the control group.

In the study they mixed NAC in the drinking water of the mice and for older mice found longer telomeres in the NAC groups compared to controls. Interestingly, they found better results for mice fed .1 nM than 1 nM... but I don't know how those concentrations would relate to a human dosage.

Howard