What are your thoughts on Lipoic Acid / CR Mimetics?

[sirtuin]

I recently picked up some Acetyl-L-carnitine (500mg) combined with racemic Alpha Lipoic Acid (150mg), after reading many reports of benefits with energy / memory / mitochondrial function, which seems like a helpful component of an anti-aging strategy.

 

While my body fat % is quite low, I've been eating an ad libitum diet for most of my life, if not a fairly high calorie diet while exercising and lifting weights / gaining muscle.  I've been dialing down on my methionine / caloric intake over the past few weeks toward a mild CR diet, and came across this article:

 

Dietary lipoic acid supplementation can mimic or block the effect of dietary restriction on life span: http://www.ncbi.nlm.nih.gov/pubmed/18486188

 

What are your thoughts on this article?  Are there other supplements / foods that nudge genetic expression toward a beneficial CR profile?

[Michael R]

I discussed this study (1) in some detail here. Basically, the benefit of adding lipoic acid to CR (a) was really rather unclear, (b] if real, was only manifested in mice that had initiated CR when young adults (6 mo/≈30 y), and (c] if real, was only manifested in mice that had been switched over from CR to AL later on in life (by blunting the loss of lifespan induced by going back on AL). Basically, if you started CR in middle age or older, and/or intend to remain on CR until rejuvenation biotechnology becomes available, the study is irrelevant to your situation.

 

In addition to still having no evidence of benefit in healthy humans, we now have at least five studies (that I know of) in which RLA ± ALCAR has failed to extend lifespan in normal mice or rats(1-5) (and yes, (3) and (4) are separate studies), and in nondiabetic, nonobese, non-sugar-stuffed rodents RLA has no effect on heart mitochondrial superoxide production,(6) plasma and aortic CML,(6) fasting glucose,(6,7) fasting insulin,(6,7) VO2_max,(7) or insulin resistance;(6,7) it has only a transient effect on blood pressure that reverses itself within four weeks,(6) and if anything may worsen free fatty acids.(7)

References
1.  Merry BJ, Kirk AJ, Goyns MH (June 2008). "Dietary lipoic acid supplementation can mimic or block the effect of dietary restriction on life span". Mech Ageing Dev 129 (6): 341–8. doi:10.1016/j.mad.2008.04.004 . PMID 18486188.

2. Lee CK, Pugh TD, Klopp RG, Edwards J, Allison DB, Weindruch R, Prolla TA (Apr 15, 2004). "The impact of alpha-lipoic acid, coenzyme Q10 and caloric restriction on life span and gene expression patterns in mice". Free Radic Biol Med 36 (8): 1043–57. doi:10.1016/j.freeradbiomed.2004.01.015 . PMID 15059645.
3. Spindler SR; Mote PL (2007). "Screening candidate longevity therapeutics using gene-expression arrays". Gerontology 53 (5): 306–21. doi:10.1159/000103924 . PMID 17570924.
4. Spindler SR; Mote PL; Flegal JM (2013 Dec). "Lifespan effects of simple and complex nutraceutical combinations fed isocalorically to mice". Age (Dordr). Online First. doi:10.1007/s11357-013-9609-9 . PMID 24370781.
5. Bruce N. Ames. Personal communication, 2003-09-21
6. Midaoui AE, Elimadi A, Wu L, Haddad PS, de Champlain J. Lipoic acid prevents hypertension, hyperglycemia, and the increase in heart mitochondrial superoxide production. Am J Hypertens. 2003 Mar;16(3):173-9. PubMed PMID: 12620694.
7. Saengsirisuwan V, Perez FR, Kinnick TR, Henriksen EJ. Effects of exercise training and antioxidant R-ALA on glucose transport in insulin-sensitive rat skeletal muscle. J Appl Physiol (1985). 2002 Jan;92(1):50-8. PubMed PMID: 11744642.