X-Message-Number: 19975
Date: Mon, 2 Sep 2002 18:20:36 EDT
Subject: Alternatives to LEF

I realized that in my first response I left out several points I consider 
important. One is about alpha lipoic acid and acetyl-l-carnitine and the 
other is about another LEF product I've seen stikingly good clinical 
(including laboratory quantifiable) responses to with specific problems:

Early on I didn't give much thought to alpha lipoic acid myself. It performed 
poorly in my acute cerebral ischemia and blunt head trauma studies and it is 
active only after being metabolized to thioctic acid (its reduced state) in 
the liver.

It also did not extend lifespan in any of the LEF funded studies that I know 
of (but my data is scanty). I think it is probably a poor monoagent for life 
extension or health benefit. Having said that, I would point to the recent 
work of Bruce Ames, et al., which shows a potent synergistic effect in 
combining alpha lipoic acid and acetyl-l-carnitine in aging.  A comprehensive 
index of the papers is given below as well as the website for full text 


Please note that acetyl-l-carnitine and the much cheaper l-carnitine are NOT 
the same. Acetylation allows penetration into the mitochondria and especially 
allows carnitine to exceed regulated transport across the blood bran barrier 
and cross it freely.

The only nutriceutical I've ever taken that caused noticeable personal 
cognitive improvement including fewer daily recorded "senior moments" and a 
markedly increased energy and mental clarity level is ChronoForte which LEF 
produces. I get some of the same benefits from alpha lipoic acid + 
acetyl-l-carntine, but they are not as pronounced. I presume the carnosine in 
the ChronoForte is helping. 

One other LEF product that is definitely without comparison is GastroPro 
(polyenylphosphatidylcholine). I have a number of friends with HIV and HCV 
infection and serious elevation of transaminases and pancreatic enzymes. 
GastroPro normalized transaminases in 11 out of 13 people I've recommended it 
to, cut pancreatic enzymes by at least 50% in all those with elevated levels 
and seemed to have caused rapid resolution of a chronic pancreatitis in one 
HIV positive person I recommended the product to. So, it is a great liver and 
pancreas protector, at least against the d4T and 3TC type drugs. A real nice 
side benefit is reduction of nausea and malaise after HIV drug dosing. 

The availability of this kind of product and watching it change peoples' 
lives dramatically makes me reluctant to be too hard on LEF. And, the fact 
remains that they really are spending millions on basic organ 
cryopreservation research with dramatic and visible results in human 
cryopatients; the first improvements since the late 1970s. I know: I've seen 
the results personally.

Mike Darwin
1.Shigenaga, M.K., T.M. Hagen, and B.N. Ames, Oxidative damage and 
mitochondrial decay in aging. Proc.
         Natl. Acad. Sci. USA, 1994. 91: p. 10771-10778.
         Abstract/PDF download

       2.Beckman, K.B. and B.N. Ames, The free radical theory of aging 
matures. Physiol. Rev., 1998. 78: p.
         Abstract/PDF download

       3.Hagen, T.M., et al., Mitochondrial decay in hepatocytes from old 
rats: Membrane potential declines,
         heterogeneity and oxidants increase. Proc. Natl. Acad. Sci. USA, 
1997. 94: p. 3064-3069.
         Abstract/PDF download

       4.Helbock, H.J., et al., DNA oxidation matters: The HPLC-EC assay of 
8-oxo-deoxyguanosine and
         8-oxo-guanine. Proc. Natl. Acad. Sci. USA, 1998. 95: p. 288-293.
         Abstract/PDF download

       5.Beckman, K.B. and B.N. Ames, Mitochondrial aging: open questions. 
Ann. N. Y. Acad. Sci., 1998. 854: p.

       6.Hagen, T.M., et al., Acetyl-L-carnitine fed to old rats partially 
restores mitochondrial function and ambulatory
         activity. Proc. Natl. Acad. Sci. USA, 1998. 95: p. 9562-9566.
         Abstract/PDF download

       7.Lykkesfeldt, J., et al., Age-associated decline in ascorbic acid 
concentration, recycling and biosynthesis in rat
         hepatocytes - reversal with (R)-alpha-Lipoic acid supplementation. 
FASEB J., 1998. 12: p. 1183-1189.
         Abstract/PDF download

       8.Hagen, T.M., et al., (R)-a-Lipoic acid-supplemented old rats have 
improved mitochondrial function,
         decreased oxidative damage, and increased metabolic rate. FASEB J., 
1998. 13: p. 411-418.
         Abstract/PDF download

       9.Hagen, T.M., C.M. Wehr, and B.N. Ames, Mitochondrial decay in aging. 
Reversal through supplementation
         of acetyl-L-carnitine and N-tert-butyl-alpha-phenyl-nitrone. Ann N Y 
Acad Sci 1998 Nov 20;854:214-23

      10.Hagen, T.M., et al., (R)-alpha-lipoic acid reverses the 
age-associated increase in susceptibility of hepatocytes
         to tertbutylhydroperoxide both in vitro and in vivo. Antiox. Redox 
Signal., 2000. 2: p. 473-483.
         Abstract/PDF download

      11.Ames, B.N., Micronutrients prevent cancer and delay aging. Toxicol. 
Lett., 1998. 102-103: p. 5-18.
         Abstract/PDF download

      12.Atamna, H., I. Cheung, and B.N. Ames, A method for detecting abasic 
sites in living cells: age-dependent
         changes in base excision repair. Proc Natl Acad Sci U S A, 2000. 
97(2): p. 686-91.
         Abstract/PDF download

      13.Blount, B.C., et al., Folate deficiency causes uracil 
misincorporation into human DNA and chromosome
         breakage: Implications for cancer and neuronal damage. Proc. Natl. 
Acad. Sci. USA, 1997. 94: p.
         Abstract/PDF download

      14.Ames, B.N. and L.S. Gold, Environmental pollution, pesticides, and 
the prevention of cancer:
         Misconceptions. FASEB J., 1997. 11: p. 1041-1052.
         Abstract/PDF download

      15.Ames, B.N., L.S. Gold, and W.C. Willett, The causes and prevention 
of cancer. Proc. Natl. Acad. Sci.
         USA, 1995. 92: p. 5258-5265.
         Abstract/PDF download

      16.Wallock, L.M., et al., Low seminal plasma folate concentrations are 
associated with low sperm density and
         count in male smokers and nonsmokers. Fertil. & Steril., 2001. 75: 
p. 252-259.
         Abstract/PDF download 

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