Anti-aging carnitine and alpha lipoic acid?

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Hi All,

It seemed to be of interest that carnitine and alpha lipoic acid may favorably

affect the reduced levels of key mitochondrial enzymes during aging. Even for

the

young, it was no so bad.

Savitha S, Sivarajan K, Haripriya D, Kokilavani V, Panneerselvam C.

Efficacy of levo carnitine and alpha lipoic acid in ameliorating the decline in

mitochondrial enzymes during aging.

Clin Nutr. 2005 Oct;24(5):794-800.

PMID: 15919137

BACKGROUND: Mitochondria are central to energy production and are therefore

fully

integrated into the rest of the cell's physiological responses to stress. The

age-related decline of capacity of each cell to manufacture energy (as ATP) is

due

to the progressive loss of structural integrity of mitochondria. It is apparent

that

as the body ages, the cells become less and less able to maintain threshold

levels

of cellular energy production. METHODS: In the present study we have evaluated

the

efficacy of carnitine, a mitochondrial metabolite and lipoic acid, a potent

antioxidant on the activities of the tri carboxylic acid (TCA) cycle enzymes

like

succinate dehydrogenase, malate dehydrogenase, alpha-ketoglutarate

dehydrogenase,

Isocitrate dehydrogenase and electron transport complex I-IV in young and aged

heart

mitochondria. RESULT: We observed that there was an age-dependent decrement in

the

levels of the TCA cycle enzymes and electron transport chain complexes.

Supplementation of carnitine (300 mg/kg bw/day) and lipoic acid (100 mg/kg

bw/day)

for 30 days brought the activities of these enzymes to almost near normal

levels.

CONCLUSION: These findings suggest that the combination of these drugs raises

the

mitochondrial energy producing capabilities by reversing the age-associated

decline

in mitochondrial enzyme activities and thereby protecting mitochondria from

aging.

.... Carnitine is a natural substance that acts as a carrier of fatty acids

across

the inner mitochondrial membrane for subsequent â-oxidation. l-carnitine and its

esters are endogenously synthesized in man and also found in diet.8 Carnitines

are

essential cofactors of several enzymes necessary for the transformation of long

chain fatty acids. Thus, we chose to administer carnitine to aged rats to

improve

the mitochondria-mediated bioenergetics. But despite the benefits of carnitine

treatment, there are also potential adverse effects. While carnitine

supplementation

reversed many of the altered characteristics evident in mitochondrial metabolism

with age, the rate of oxidant production was higher in carnitine-supplemented

rats.9

We further observed that the age-related increase in oxidant production and

oxidative damage can be reversed by co-supplementation with á-lipoic acid, a

disulfide compound found naturally in plants and animals.10 The disulfide form

of

lipoic acid is reduced in mitochondria by specific dehydrogenase and its

supplementation would thus target an antioxidant to the mitochondria, the major

site

of free radical production.11 Supplementation with LA may also boost

mitochondrial

function because it is a co-factor for pyruvate and á-ketoglutarate

dehydrogenase12

and 13 and as such, may be a useful dietary supplement in its own right to

increase

overall mitochondrial metabolism.

.... Male albino rats of Wistar strain approximately 3–4-months-old (young) and

above

24-months-old (aged) were used in this study. They were healthy animals procured

from The King's Institute of Preventive Medicine, Chennai. The animals were

housed

in large spacious cages and were given food and water ad libitum. The animal

room

was well ventilated and had 12 h light/dark cycles throughout the experimental

period. The animals were maintained on a commercial rat feed which contained 5%

fat,

21% protein, 55% nitrogen-free extract and 4% fiber (wt/wt) with adequate

mineral

and vitamin contents.

.... Table 1. Effect of carnitine and lipoic acid on the TCA cycle enzymes of

heart

mitochondria in young and aged rat.

=========================================

Parameters Young control Young combination Aged control Aged+carnitine

Aged+lipoic

acid Aged combination

=========================================

Succinate dehydrogenase 39.83±4.71 41±4.69 27.17±2.93* 33.17±3.54lk and lk

32±3.46lk

and lk 38.25±3.09†

Malate dehydrogenase 21.13±2.37 21.83±2.54 14.08±1.43* 17.12±1.70lk and lk

16.67±1.99lk and lk 20.08±2.50†

Isocitrate dehydrogenase 13.01±1.41 13.26±1.59 8.70±1.08* 10.44±0.16lk and lk

10.27±1.18lk and lk 12.02±1.41†

á-ketoglutarate dehydrogenase 8.92±1.07 9.44±1.16 5.75±0.71* 7.27±0.81lk and lk

7.02±0.80lk and lk 8.58±1.02†

=========================================

Values are expressed as mean ± SD for six rats in each group.

Succinate dehydrogenase, micromoles of succinate oxidized per min per mg

protein;

malate dehydrogenase, nanomoles of NADH oxidized per min per mg protein,

isocitrate

dehydrogenase, nanomoles of á-ketoglutarate formed per min per mg protein;

á-ketoglutarate dehydrogenase, micromoles of potassium ferrocyanide liberated

per

min per mg protein.

* Differences compared with young control rats.

† Differences compared with aged control rats.

‡ Differences compared with aged rats treated with carnitine and lipoic acid.

....the utilization of carnitine and lipoic acid can lead to an improvement in

the

quality of living during the later stages of life by revitalizing the

mitochondria

and reversing the declining level of the body's energy metabolism.

Al Pater, PhD; email: old542000@...

__________________________________

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