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The supplement did nothing for me, but it is very good it may be what you

need. Here's some information from my files.

Information Alpha Lipolic Acid

Studies strongly support supplementation with ALA, A L Carnitine, and Co

Enzyme Q10 for increased energy within in the cells.

Studies show ALA reduced CATARACT FORMATION by 45% in Rats!

Studies show ALA reduces oxidative stress in the heart muscle while raising

levels in heart and liver energy (mitochondria).

Studies show ALA's special property of chelating free iron from brain cells,

and enhancement of vility to regenerate ascorbate.

ALPHA LIPOIC ACID PREVENTS BRAIN-AGING. Part of the pathology of brain aging

is an increase in the levels of iron with a parallel decrease in vitamin C

in the tissue. This leads to increased levels of free radicals in brain cells

and subsequent neuronal dysfunction and death.

to

At The Linus ing Institute, studies demonstrated that a significant

reversal of this pattern in rats receiving 4 mg. per day of lipoic acid. Lipoic

acid reduced total levels of iron of the forebrain and a substantial increase

in the forebrain vitamin C levels. This suggests that the forebrain, a region

involved in cognition has a special facility for the uptake and metabolism

of lipoic acid.

Scientists speculate it has the special property of chelating free iron from

brain cells, IMPROVING MITOCHONDRIAL FUNCTION AND PROTECTING AGAINST FREE

RADICALS AND ENHANCING BRAIN CELL REGENERATION.

Another study reported that lipoic acid reduces oxidative stress in the

heart muscle while raising glutathione and ascorbate levels in the heart and

liver mitochondria. Researchers recommend lipoic acid as a therapy to prevent

cataract formation. Lipoic has the ability to maintain glutathione in the eye

lens.

Lipoic regulates oxidation of fats and sugars into energy, maintains the

critical Kreb's energy production cycle and is able to lower blood glucose

levels and prevent the formation of glycation products. GLYCOSYLATION is the

abnormal binding of a glucose molecule to a protein molecule to form a

non-functioning structure in the body. The inhibition of glycation is critical

to

diabetics and can slow aging (and wrinkles) in healthy people.

* LOWERS GLUCOSE LEVELS BY INCREASING INSULIN METABOLISM AND DECREASES

NUMBNESS IN DIABETICS

* INCREASES ENERGY LEVELS WITHIN CELLS

* CAN DECREASE CHOLESTEROL AND PROTEIN OXIDATION FOR A HEALTHY HEART

ALPHA LIPOIC ACID inhibits free radicals more effectively than vitamin E.

ALA is an important supplement in the prevention of HEART DISEASE.

ALPHA LIPOIC ACID inhibits the oxidation of protein, AIDS MITOCHONDRIAL

ENERGY METABOL which he are on ISM, and lowers LDL cholesterol.

a-LIPOIC ACID

Also known as thioctic acid, a-lipoic acid is a naturally occurring compound

that is synthesized by plants and animals, including humans. a-Lipoic acid

contains two sulfur molecules that can be _oxidized_

(http://lpi.oregonstate.edu/infocenter/glossary.html#oxidation) or _reduced_

(http://lpi.oregonstate.edu/infocenter/glossary.html#reduction) . This feature

allows a-lipoic acid to

function as a _cofactor_

(http://lpi.oregonstate.edu/infocenter/glossary.html#cofactor) for several

important _enzymes_

(http://lpi.oregonstate.edu/infocenter/glossary.html#enzyme) as well as a

potent _antioxidant_

(http://lpi.oregonstate.edu/infocenter/glossary.html#antioxidant) . Only the

R-_isomer_

(http://lpi.oregonstate.edu/infocenter/glossary.html#isomers) of a-lipoic acid

is

synthesized naturally. Conventional chemical synthesis of a-lipoic acid results

in a 50/50 (racemic) mixture of the two optical isomers, R-a-lipoic acid and

S-a-lipoic acid. _(1)_

(http://lpi.oregonstate.edu/infocenter/othernuts/la/#reference) . In the text

that follows, the term " a-lipoic acid " refers to

racemic a-lipoic acid, while " R-a-lipoic acid " or " S-a-lipoic acid " refers to

the specific isomer.

FUNCTION

Enzyme cofactor

R-a-Lipoic acid is normally bound to _proteins_

(http://lpi.oregonstate.edu/infocenter/glossary.html#protein) by linkage of its

carboxyl (COOH) group to

a lysine _residue_

(http://lpi.oregonstate.edu/infocenter/glossary.html#residue) in the protein.

In its protein bound form, lipoamide, R-a-lipoic acid is

a required _cofactor_

(http://lpi.oregonstate.edu/infocenter/glossary.html#cofactor) for several

multi-enzyme complexes that _catalyze_

(http://lpi.oregonstate.edu/infocenter/glossary.html#catalyze) critical energy

_metabolism_

(http://lpi.oregonstate.edu/infocenter/glossary.html#metabolism) reactions

inside the _mitochondria_

(http://lpi.oregonstate.edu/infocenter/glossary.html#mitochondria) . The

pyruvate dehydrogenase complex catalyzes the conversion of

pyruvate to acetyl-CoA, an important _substrate_

(http://lpi.oregonstate.edu/infocenter/glossary.html#substrate) for energy

production, via the citric acid

cycle. The a-ketoglutarate dehydrogenase complex catalyzes another important

citric acid cycle reaction. The branched-chain a-keto acid dehyrogenase

complex catalyzes the metabolism of three _amino acids_

(http://lpi.oregonstate.edu/infocenter/glossary.html#amino acid) , leucine,

isoleucine, and valine,

also known as branched-chain amino acids. The glycine cleavage system is a

multi-enzyme complex that catalyzes the formation of 5,10 methylene

tetrahydrofolate, an important cofactor in _nucleic acid_

(http://lpi.oregonstate.edu/infocenter/glossary.html#nucleic acid) synthesis

_(2)_

(http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref2) .

Antioxidant

When large amounts of free a-lipoic acid are available (e.g., with

supplementation), a-lipoic acid is also able to function as an antioxidant

_(3)_

(http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref3) . a-Dihydrolipoic

acid

(DHLA) is the reduced form of a-lipoic acid, and is the only form that

functions directly as an _antioxidant_

(http://lpi.oregonstate.edu/infocenter/glossary.html#antioxidant) (_structure_

(http://lpi.oregonstate.edu/infocenter/othernuts/la/la%20structure.html) ). Free

a-lipoic acid is rapidly taken up by

cells and reduced to DHLA intracellularly. Because DHLA is also rapidly

eliminated from cells, the extent to which its antioxidant effects can be

sustained

remain unclear. Although only DHLA functions directly as an antioxidant,

a-lipoic acid may have indirect antioxidant effects _(4)_

(http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref4) .

Chelation of metal ions: Certain free metal ions like iron and copper can

induce oxidative damage by catalyzing reactions that generate highly reactive

_free radicals_ (http://lpi.oregonstate.edu/infocenter/glossary.html#free

radical) . Both a-lipoic acid and DHLA may _chelate_

(http://lpi.oregonstate.edu/infocenter/glossary.html#chelate) or bind metal

ions in a way that prevents

them from generating free radicals _(1)_ (http://lpi

..oregonstate.edu/infocenter/othernuts/la/#reference) . At present, this property

has only been

demonstrated in the test tube and in _extracellular fluids_

(http://lpi.oregonstate.edu/infocenter/glossary.html#extracellular fluid) .

Scavenging free radicals: DHLA may prevent oxidative damage by interacting

with potentially damaging _reactive oxygen species_

(http://lpi.oregonstate.edu/infocenter/glossary.html#reactive oxygen species)

(ROS) and _reactive

nitrogen species_ (http://lpi.oregonstate.edu/infocenter/glossary.html#reactive

nitorogen species) (RNS) _(5)_

(http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref5) .

Regenerating other antioxidants: When an antioxidant like vitamin C

neutralizes a free radical, it becomes oxidized itself, and is not able to

neutralize

other free radicals until it has been reduced or regenerated. DHLA is a

potent reducing agent, and has the capacity to regenerate a number of oxidized

antioxidants to their active antioxidant forms (_diagram_

(http://lpi.oregonstate.edu/infocenter/othernuts/la/la%20antiox%20network.html)

). Specifically,

DHLA is capable of reducing the oxidized forms of vitamin C, _glutathione_

(http://lpi.oregonstate.edu/infocenter/glossary.html#glutathione) , and coenzyme

Q10, which are able to regenerate oxidized a-tocopherol (vitamin E), forming an

antioxidant network. DHLA can be regenerated from a-lipoic acid through the

activity of _enzymes_

(http://lpi.oregonstate.edu/infocenter/glossary.html#enzyme) present in cells

_(1)_

(http://lpi.oregonstate.edu/infocenter/othernuts/la/#reference) .

Increasing intracellular glutathione levels: Glutathione is an important

water-soluble antioxidant that is synthesized from the sulfur-containing _amino

acid_ (http://lpi.oregonstate.edu/infocenter/glossary.html#amino acid)

cysteine. The availability of cysteine inside a cell determines its rate of

glutathione synthesis. DHLA has been found to increase the uptake of cysteine

by

cells in culture, leading to increased glutathione synthesis _(1)_

(http://lpi.oregonstate.edu/infocenter/othernuts/la/#reference) . Although

increases in

intracellular DHLA are short-lived, DHLA may also improve intracellular

antioxidant capacity by inducing glutathione synthesis.

Repair of oxidative damage: The protein, a1-antiprotease, is an inhibitor of

the enzyme elastase. _Oxidation_

(http://lpi.oregonstate.edu/infocenter/glossary.html#oxidation) inactivates

a1-antiprotease, leading to increased

activity of elastase and degradation of elastin in the lungs, a process that has

been implicated in _chronic obstructive pulmonary disease (COPD)_

(http://lpi.oregonstate.edu/infocenter/glossary.html#chronic obstructive

pulmonary disease)

.. In the test tube, DHLA can act as a reducing factor for the enzyme,

peptide methionine sulfoxide reductase (PMSR), which can reduce and reactivate

oxidized a1-antiprotease _(6)_

(http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref6) . Whether a-lipoic

acid contributes to the repair of oxidized

proteins in living organisms remains to be determined.

Regulation of gene transcription

The protein, NF-kappaB (NF-kB), is known as a _transcription factor_

(http://lpi.oregonstate.edu/infocenter/glossary.html#transcription factor)

because it

is able to bind to DNA and affect the rate of _transcription_

(http://lpi.oregonstate.edu/infocenter/glossary.html#transcription) of certain

_genes_

(http://lpi.oregonstate.edu/infocenter/glossary.html#gene) that have NF-kB

binding sites. NF-kB plays an important role in regulating genes related to

inflammation and the pathology of a number of diseases, including

_atherosclerosis_

(http://lpi.oregonstate.edu/infocenter/glossary.html#atherosclerosis) ,

cancer, and _diabetes_

(http://lpi.oregonstate.edu/infocenter/glossary.html#diabetes) _(2)_

(http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref2) .

Physiologically relevant concentrations of a-lipoic acid have been found to

inhibit

the activation of NF-kB when added to cells in culture _(7)_ (http://lpi.orego

nstate.edu/infocenter/othernuts/la/#ref7) .

AP-1 is another transcription factor that can be affected by both reactive

oxygen species (ROS) and certain antioxidants within cells. Treating cells in

culture with DHLA has been found to inhibit the activity of AP-1 by

decreasing the expression of c-fos, one of the proteins that makes up the

functional

AP-1 complex _(8)_ (http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref8) .

DEFICIENCY

a-Lipoic acid deficiency has not been described, suggesting that humans are

able to synthesize enough to meet their needs for _enzyme_

(http://lpi.oregonstate.edu/infocenter/glossary.html#enzyme) _cofactors_

(http://lpi.oregonstate.edu/infocenter/glossary.html#cofactors) . Increased

destruction of the

cofactor form of a-lipoic acid may underlie the pathology of some diseases. In

arsenic toxicity, arsenic can form a complex with a-lipoic acid in

dehydrogenase

enzymes, leaving it inactive _(3)_

(http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref3) . Circulating

antibodies to lipoamide-containing enzyme

subunits have been isolated in patients with an _autoimmune_

(http://lpi.oregonstate.edu/infocenter/glossary.html#autoimmune disease) liver

disease known as

primary biliary cirrhosis _(9)_

(http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref9) .

DISEASE PREVENTION

Aging

_Mitochondria_

(http://lpi.oregonstate.edu/infocenter/glossary.html#mitochondria) are cellular

organelles that oxidize dietary fuels (proteins, fats, and

carbohydrates) to a usable form of energy, adenosine triphosphate (_ATP_

(http://lpi.oregonstate.edu/infocenter/glossary.html#atp) ). _Free radicals_

(http://lpi.oregonstate.edu/infocenter/glossary.html#free radical) or _reactive

oxygen species_ (http://lpi.oregonstate.edu/infocenter/glossary.html#reactive

oxygen species) (ROS) are also produced by mitochondria as a byproduct of

energy production. If not neutralized by antioxidants, ROS may damage

mitochondria over time, causing them function less efficiently and to generate

more

damaging ROS in a self-perpetuating cycle. Many experts feel that this

deterioration in mitochondrial function is directly related to functional

declines in

aging and age-related diseases _(10)_

(http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref10) . In aging rats,

short-term dietary supplementation with

R-a-lipoic acid has been found to decrease mitochondrial ROS production and

improve mitochondrial function _(11, 12)_

(http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref11) . A series of

studies in aged rats found that

combined dietary supplementation of R-a-lipoic acid and acetyl-L-carnitine

improved

mitochondrial energy metabolism, decreased oxidative stress, increased

physical activity, and improved measures of short-term memory _(13, 14)_

(http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref13) . Acetyl-L-carnitine

is a

supplemental form of L-carnitine, an amino acid derivative that plays a crucial

role in mitochondrial energy metabolism. (See L-carnitine for more

information.) While these findings are very encouraging, the researchers caution

that

these studies used relatively high doses of the compounds for only for one

month. It is not yet known whether taking relatively high doses of R-a-lipoic

acid and acetyl-L-carnitine will benefit aging rats in the long-term or will

have similar effects in humans. Clinical trials of a combination supplement of

a-lipoic acid and acetyl-L-carnitine in humans currently underway, but the

results of these trials are not yet available for evaluation.

For more information about aging and oxidative stress, see the article,

_Aging with Dr. Tory Hagen_ (http://lpi.orst.edu/f-w00/aging.html) , in the

Fall/Winter 2000 LPI Newsletter.

DISEASE TREATMENT

Diabetes

Chronically elevated blood glucose levels are the hallmark of _diabetes

mellitus_ (http://lpi.oregonstate.edu/infocenter/glossary.html#diabetes) . Type

I

diabetes is also known as juvenile-onset or insulin-dependent diabetes

mellitus (IDDM) because it often develops in childhood or adolescence, and

insulin

therapy is required to control blood glucose levels. Type II diabetes is also

known as adult-onset diabetes or non-insulin-dependent diabetes mellitus

(NIDDM) because it is more common in older adults and may not require insulin

therapy. However, type II diabetes may also develop in children and

adolescents, and its treatment may eventually require insulin therapy.

_Pharmacologic

doses_ (http://lpi.oregonstate.edu/infocenter/glossary.html#pharmacologic dose)

of a-lipoic acid (i.e., many times higher than the amount a person could

synthesize or obtain from foods) have been prescribed to treat diabetic

patients

in Germany since the late 1960's _(4)_

(http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref4) . Below is a summary

of research on the use of a-lipoic

acid supplementation to treat diabetes and its complications.

Insulin sensitivity: In type II diabetes, elevated blood glucose levels

result from _insulin resistance_

(http://lpi.oregonstate.edu/infocenter/glossary.html#insulin resistance) rather

than a lack of insulin, and a number of

treatments have been aimed at improving insulin sensitivity. There is limited

evidence that high doses of a-lipoic acid can improve insulin sensitivity in

individuals with type II diabetes. Intravenous infusions of 600 mg _(15)_

(http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref15) and 1,000 mg _(16)_

(http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref16) of a-lipoic acid to

type II diabetics, improved insulin sensitivity by 27% and 51%, respectively

compared to a placebo. An uncontrolled study of 20 type II diabetics found that

oral administration of 1,200 mg of a-lipoic acid for 4 weeks significantly

improved measures of glucose metabolism _(17)_

(http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref17) , and a

placebo-controlled study of 72 type II

diabetics found that oral a-lipoic acid at doses of 600 mg/day, 1,200 mg/day or

1,800 mg/day for 4 weeks improved insulin sensitivity by 25% _(18)_

(http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref18) . However, there

were no

significant differences between the three doses of a-lipoic acid tested. All of

these studies were conducted using racemic a-lipoic acid. Data from animal

studies suggests that the R-isomer may be more effective in improving insulin

sensitivity than the S-isomer _(19, 20)_

(http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref19) , but this

possibility has not been tested in any

published human trials.

Oxidative stress: A number of studies in individuals with diabetes (type I

and type II) indicate that they are under increased _oxidative stress_

(http://lpi.oregonstate.edu/infocenter/glossary.html#oxidative stress) , a

condition

that is believed to contribute to the vascular and neurologic complications

of diabetes. Although a-lipoic acid supplementation has been found to reduce

measures of oxidative stress in animal models of diabetes, evidence that

a-lipoic acid reduces oxidative stress in humans with diabetes is limited. In a

non-randomized _cross-sectional study_

(http://lpi.oregonstate.edu/infocenter/glossary.html#cross-sectional study) , 33

patients with type I or type II

diabetes who had been taking 600 mg/day of a-lipoic acid orally for at least 3

months had lower levels of _plasma_

(http://lpi.oregonstate.edu/infocenter/glossary.html#plasma) _lipid

peroxidation_

(http://lpi.oregonstate.edu/infocenter/glossary.html#lipid peroxidation) than

did 74 diabetics who did not take

a-lipoic acid _(21)_ (http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref21)

.. An intervention trial in 10 diabetic patients found that plasma lipid

peroxides were significantly lower after taking 600 mg/day of a-lipoic acid

orally for 60 days compared to baseline _(22)_

(http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref22) . The NF-kB

transcription factor is known to increase

the transcription of genes related to inflammation in response to increased

oxidative stress. Oral a-lipoic acid supplementation (600 mg/day) has been

found to decrease NF-kB activation in the white blood cells of type I diabetics

_(23) _ (http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref23) and

patients with diabetic nephropathy (kidney damage) _(24)_

(http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref24) . The formation of

advanced glycation end

products (AGEP) also leads to glucose-mediated damage in diabetes. a-Lipoic

acid has been found to prevent the formation of AGEP in the test tube _(25)_

(http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref25) .

Diabetic peripheral neuropathy: Over one third of diabetics develop

peripheral _neuropathy_

(http://lpi.oregonstate.edu/infocenter/glossary.html#neuropathy) , a type of

nerve damage that may result in decreased sensitivity,

numbness, and pain, particularly in the lower extremities. In addition to the

pain

and disability caused by diabetic neuropathy, it is a leading cause of lower

limb amputation in diabetics _(26)_

(http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref26) . The results of

several large _randomized controlled trials_

(http://lpi.oregonstate.edu/infocenter/glossary.html#randomized controlled

trial) indicate that maintaining blood glucose at near normal levels is the

most important step in decreasing the risk of diabetic neuropathy _(27, 28)_

(http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref27) . However, such

intensive blood glucose control may not be achievable in all diabetic patients.

Oxidative stress has been implicated in the pathology of diabetic neuropathy,

and a-lipoic acid is approved for the treatment of diabetic neuropathy in

Germany _(1)_ (http://lpi.oregonstate.edu/infocenter/othernuts/la/#reference) .

At least 15 clinical trials have examined the effect of a-lipoic acid

treatment on symptoms of diabetic neuropathy with mixed results, especially in

smaller studies _(29)_

(http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref29)

.. Modest benefits have been observed in several large multi-center trials.

More than 300 type II diabetics with symptomatic peripheral neuropathy were

randomly assigned to intravenous treatment with 100 mg/day, 600 mg/day, or

1,200 mg/day of a-lipoic acid or _placebo_

(http://lpi.oregonstate.edu/infocenter/glossary.html#placebo) for 3 weeks

_(30)_

(http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref30) . Symptom scores

were significantly improved in

those that received intravenous infusions of at least 600 mg/day of a-lipoic

acid

compared to placebo. A subsequent multi-center trial randomly assigned 509

type II diabetics with symptomatic peripheral neuropathy to one of three

treatments: 1) 600 mg/day of intravenous a-lipoic acid for 3 weeks followed by

1,800 mg/day of oral a-lipoic acid (600 mg, 3 times/day) for 6 months, 2) 600

mg/day of intravenous a-lipoic acid for 3 weeks followed by oral placebo for 6

months, or 3) intravenous placebo for 3 weeks followed by oral placebo for 6

months _(31)_ (http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref31) .

Although symptom scores did not differ significantly from baseline in any of

the groups, assessments of sensory and motor deficits by trained physicians

were significantly improved after 3 weeks of intravenous a-lipoic acid therapy

and non-significantly improved at the end of 6 months of oral a-lipoic acid

therapy. A smaller randomized controlled trial examined the effect of long-term

oral a-lipoic acid supplementation on the results of electrophysiologic

nerve conduction studies in 65 diabetic patients with symptomatic peripheral

neuropathy _(32)_ (http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref32) .

After two years of follow up, those who took either 600 mg/day or 1,200 mg/day

of a-lipoic acid orally showed significant improvements in 3 out of 4 nerve

conduction assessments compared to those who took placebo.

Overall, the available research suggests that oral doses of at least 600

mg/day of a-lipoic acid may offer some benefit in the alleviation of

neuropathic

symptoms and deficits, especially when used in conjunction with effective

treatment aimed at normalizing blood glucose levels.

Vascular complications: The inner lining of blood vessels, known as the

_endothelium_ (http://lpi.oregonstate.edu/infocenter/glossary.html#endothelium)

,

plays an important role in preventing vascular disease. Endothelial function

in individuals with diabetes (type I and type II) is often impaired, and

diabetics are at increased risk for vascular disease. Several small preliminary

studies in humans have examined the effect of a-lipoic acid administration on

endothelial function. In one study, intra-arterial infusions of a-lipoic acid

improved endothelium-dependent _vasodilation_

(http://lpi.oregonstate.edu/infocenter/glossary.html#vasodilation) (blood

vessel relaxation) in 39 diabetic

patients, but not in 11 healthy controls _(33)_

(http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref33) . Oral

supplementation of 1,200 mg/day of

a-lipoic acid for 6 weeks improved a measure of capillary perfusion in the

fingers

of 8 diabetic patients with peripheral neuropathy _(34)_

(http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref34) . In an

uncontrolled, non-randomized

study of 84 diabetic patients, plasma thrombomodulin levels, a marker of

compromised endothelial function, decreased significantly in the 35 diabetics

that

took 600 mg/day of a-lipoic acid orally over 18 months, while thrombomodulin

levels increased significantly in those that did not take a-lipoic acid over

the same period _(35)_

(http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref35) . While the results

of these small, uncontrolled trials are

encouraging, long-term placebo-controlled studies are needed before it can be

determined

whether a-lipoic acid supplementation can reduce the risk of vascular

complications in individuals with diabetes.

SOURCES

Biosynthesis

a-Lipoic acid can be synthesized by plants and animals. The biosynthetic

pathway for a-lipoic acid is not known, but it appears to be synthesized in the

mitochondria from an 8-carbon _fatty acid_

(http://lpi.oregonstate.edu/infocenter/glossary.html#fatty acid) and elemental

sulfur _(5)_

(http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref5) . It is currently

unclear whether

synthesis by normal _gastrointestinal_

(http://lpi.oregonstate.edu/infocenter/glossary.html#gastrointestinal) bacteria

is a significant source of a-lipoic

acid in humans. Biosynthesis does not appear to result in large amounts of

circulating free a-lipoic acid, the form that is likely to function as an

antioxidant _(3)_ (http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref3) .

Food sources

Most a-lipoic acid in food is derived from lipoamide-containing _enzymes_

(http://lpi.oregonstate.edu/infocenter/glossary.html#enzyme) and is bound to

the _amino acid_ (http://lpi.oregonstate.edu/infocenter/glossary.html#amino

acid) , lysine (lipoyllysine). Animal tissues that are rich in lipoyllysine

include kidney, heart, and liver, while plant sources that are rich in

lipoyllysine include spinach, broccoli, and tomatoes. Somewhat lower amounts of

lipoyllysine have been measured in peas, brussel sprouts, and rice bran _(36)_

(http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref36) . Digestive enzymes

do

not break the bond between a-lipoic acid and lysine very effectively. Thus, it

has been hypothesized that most dietary a-lipoic acid is absorbed as

lipoyllysine, and free a-lipoic acid has not been detected in the circulation

of

humans who are not taking a-lipoic acid supplements _(3)_

(http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref3) . Although a-lipoic

acid is found in a

wide variety of foods from plant and animal sources, quantitative information

on the a-lipoic acid content of food is limited. In the table below, the

a-lipoic acid content of some foods was calculated from measurements of

lipoyllysine in freeze-dried food samples _(36)_

(http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref36) .

Food

Lipoyllysine

(mg/g dry weight)

Serving

a-lipoic acid*/serving

(mg)#

Beef kidney

2.6

3 ounces (85 g)

32

Beef heart

1.5

3 ounces (85 g)

19

Beef liver

0.9

3 ounces (85 g)

14

Spinach

3.2

1 cup raw (30 g)

5

Broccoli

0.9

1 cup raw (71 g)

4

Tomato

0.6

1 medium (123 g)

3

Peas

0.4

1 cup raw (145 g)

7

Brussel sprouts

0.4

1 cup raw (88 g)

3

Rice bran

0.2

1 cup (118 g)

11

Egg yolk

0.05

1 large (17 g)

0.3

*Lipoyllysine x 0.62 = a-lipoic acid _(1)_

(http://lpi.oregonstate.edu/infocenter/othernuts/la/#reference)

#1,000 micrograms (mg) = 1 milligram (mg)

Supplements

Supplemental doses of a-lipoic acid are hundreds of times higher than the

amounts that can be obtained from food, and should be considered _pharmacologic_

(http://lpi.oregonstate.edu/infocenter/glossary.html#pharmacologic dose)

rather than _physiologic doses_

(http://lpi.oregonstate.edu/infocenter/glossary.html#physiologic dose) .

a-Lipoic acid is available by prescription in

Germany, where it is approved for the treatment of diabetic and alcoholic

_neuropathies_ (http://lpi.oregonstate.edu/infocenter/glossary.html#neuropathy)

and

alcoholic liver disease. It is available in the U.S. as a dietary supplement

_(37)_ (http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref37) . Presently,

all supplements available in the U.S. contain racemic a-lipoic acid, also

called R-, S-a-lipoic acid or D-, L-a-lipoic acid.

a-Lipoic acid from supplements is rapidly absorbed, rapidly metabolized, and

rapidly cleared from plasma and tissues, suggesting that it should be taken

in divided doses throughout the day, rather than in a single daily dose. The

bioavailability of an orally administered dose of 200 mg is about 20-30% that

of an intravenous dose _(38, 39)_

(http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref38) . Recommendations

for the use of racemic a-lipoic acid as an

_antioxidant_

(http://lpi.oregonstate.edu/infocenter/glossary.html#antioxidant) range from 50

mg/day to 400 mg/day. In the only published study to

examine the _in vivo_ (http://lpi.oregonstate.edu/infocenter/glossary.html#in

vivo)

antioxidant effects of a-lipoic acid in healthy humans, 600 mg/day for 4

months significantly decreased several _biomarkers_

(http://lpi.oregonstate.edu/infocenter/glossary.html#biomarker) of oxidative

stress compared to baseline

_(40)_ (http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref40) . However,

the antioxidant effects of lower doses have not been well studied in

humans.

Racemic vs. R-a-lipoic acid: There is evidence that the two optical _isomers_

(http://lpi.oregonstate.edu/infocenter/glossary.html#isomers) of a-lipoic

acid have different biological activities. R-a-lipoic acid occurs naturally in

plants and animals and is the only form that functions as a _cofactor_

(http://lpi.oregonstate.edu/infocenter/glossary.html#cofactor) for

mitochondrial

enzymes (see _Function_

(http://lpi.oregonstate.edu/infocenter/othernuts/la/#function) ). Chemical

synthesis of a-lipoic acid results in a 50/50 or racemic

mixture of S-a-lipoic acid and R-a-lipoic acid. Within the _mitochondria_

(http://lpi.oregonstate.edu/infocenter/glossary.html#mitochondria) , R-a-lipoic

acid is reduced to DHLA, the more potent antioxidant, 28 times faster than

S-a-lipoic acid. However, in the cytosol S-a-lipoic acid is reduced to DHLA

twice

as fast as R-a-lipoic acid. One study in humans found R-a-lipoic acid to be

more _bioavailable_

(http://lpi.oregonstate.edu/infocenter/glossary.html#bioavailable) than

S-a-lipoic acid when taken orally _(38)_

(http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref38) . R-lipoic acid was

more effective than

S-lipoic acid in enhancing insulin-stimulated glucose transport and metabolism

in insulin-resistant rat skeletal muscle _(19)_

(http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref19) , and R-a-lipoic

acid was more effective than

racemic a-lipoic acid and S-a-lipoic acid in preventing cataracts in rats

_(41)_ (http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref41) . Almost all

studies of a-lipoic acid supplementation in humans have been performed using

racemic a-lipoic acid. At present, it is not known whether R-a-lipoic acid is

more effective as an antioxidant than racemic lipoic acid when taken by

humans in _pharmacologic doses_

(http://lpi.oregonstate.edu/infocenter/glossary.html#pharmacologic dose) .

SAFETY

Toxicity

In general, a-lipoic acid doses of 600 mg/day have been well tolerated.

Doses as high as 1,200 mg/day (600 mg, 2 times/day) for 2 years and 1,800

mg/day

(600 mg, 3 times/day) for 3 weeks did not result in adverse effects when

given to patients with diabetic neuropathy under medical supervision. There are

no reports of toxicity from a-lipoic acid overdose in humans. In individuals

with diabetes and/or _impaired glucose tolerance_

(http://lpi.oregonstate.edu/infocenter/glossary.html#impaired glucose tolerance)

, a-lipoic acid

supplementation may lower blood glucose levels. Individuals on diabetic

medications

should monitor blood glucose levels. Diabetic medication doses may need to be

adjusted to avoid _hypoglycemia_

(http://lpi.oregonstate.edu/infocenter/glossary.html#hypoglycemia) . Because

controlled safety studies in pregnant and

lactating women are not available, the use of a-lipoic acid supplements by

pregnant or breastfeeding women is not recommended _(37)_

(http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref37) .

Drug Interactions

a-Lipoic acid supplements may affect the optimal dose of medications used to

control blood glucose in diabetics. Individuals on such hypoglycemic agents

should monitor their blood glucose levels and consult their health care

provider for dosage adjustments if necessary to prevent _hypoglycemia_

(http://lpi.oregonstate.edu/infocenter/glossary.html#hypoglycemia) _(37)_

(http://lpi.oregonstate.edu/infocenter/othernuts/la/#ref37) .

SUMMARY

* R-a-lipoic acid functions as a critical _cofactor_

(http://lpi.oregonstate.edu/infocenter/glossary.html#cofactor) in several

important _enzymes_

(http://lpi.oregonstate.edu/infocenter/glossary.html#enzyme) related to

energy metabolism.

* a-Lipoic acid deficiency has not been described, suggesting that

humans are able to synthesize enough to meet their needs for enzyme cofactors.

* In doses achievable through supplementation, a-lipoic acid can act as

an _antioxidant_

(http://lpi.oregonstate.edu/infocenter/glossary.html#antioxidant) .

* Controlled clinical trials indicate that 600 mg/day of racemic

a-lipoic acid may reduce symptoms and neurological deficits associated with

diabetic neuropathy.

* Although recent studies in rats suggest that supplementation with the

combination of R-a-lipoic acid and acetyl-L-carnitine may be beneficial in

preventing age-related declines in energy metabolism and memory, it is not

known whether supplementation with these compounds will help prevent such

age-related declines in humans.

* Although generally well tolerated, a-lipoic acid supplementation may

affect the optimal dose of medications used to control blood glucose in

diabetics or precipitate _hypoglycemia_

(http://lpi.oregonstate.edu/infocenter/glossary.html#hypoglycemia) .

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& dopt=Abstract)

____________________________________

Reviewed by:

_Tory M. Hagen, Ph.D._ (http://lpi.oregonstate.edu/staff/hagenbio.html)

Principal Investigator, Linus ing Institute

Assistant Professor, Dept. of Biochemistry and Biophysics

Oregon State University

Last updated 08/19/2002 Copyright 2002 by The Linus ing Institute

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

3.Alpha Lipolic Acid

May naturally in body cells as byproducts of energy release, A. L. A.

increases levels of intracellular glutathione, and is a natural antioxidant with

free radical scavenging abilities. It has the ability to regenerate oxidize

antioxidants like vitamin C and E. and helps to make them more potent ALA is

also known for its ability to enhance glucose uptake and may help prevent the

cellular damage accompanying the complications of diabetes, it also has

protective effect.

Jeff el

_http://www.msprotocols.netfirms.com/_ (http://www.msprotocols.netfirms.com/)

_http://www.msprotocols.netfirms.com/Getting%20Started.htm_

(http://www.msprotocols.netfirms.com/Getting%20Started.htm)

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Sue I wish you much success, what are you looking to accomplish , maybe I

could steer you in the right direction.

Your not making a mistake for trying this, it is a very good product for

some people it works very well.

Jeff el

_http://www.msprotocols.netfirms.com/_ (http://www.msprotocols.netfirms.com/)

_http://www.msprotocols.netfirms.com/Getting%20Started.htm_

(http://www.msprotocols.netfirms.com/Getting%20Started.htm)

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You may want to research Ginkgo this works on the brain circulation, this

may increase the oxygen. There are other benefits. Sometimes it's combined

with Hawthorne Berry.

Jeff el

_http://www.msprotocols.netfirms.com/_ (http://www.msprotocols.netfirms.com/)

_http://www.msprotocols.netfirms.com/Getting%20Started.htm_

(http://www.msprotocols.netfirms.com/Getting%20Started.htm)

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