Alpha Lipoic Acid

Laura

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I just read "The Alpha Lipoic Acid Breakthrough" and want to recommend the book and the supplement! The author isn't pushing anything, not even his own "plan" so you won't find any recommendations other than very sensible ones that fit well with all we have already learned about diet and detoxing. What is important about this book is the clear way he describes several bio-chemical systems of the body so that anyone can understand what is going on especially in respect of the damage that toxicity can do to your body at the DNA level, and how to ameliorate this.

Alpha Lipoic Acid should, apparently, be high on anyone's list of detox supplements and even when you slack off on many of them, once certain conditions are corrected, you should probably keep taking ALA. It goes directly into the body and works on a cellular level to restore energy metabolism. Many experts say that if you have insulin resistance, fibromyalgia, chronic fatigue, you should be taking this one regularly.

Here are some links to articles about it that are available on the web:

http://www.umm.edu/altmed/articles/alpha-lipoic-000285.htm

Alpha-lipoic acid
Overview:

Alpha-lipoic acid is an antioxidant that is made by the body and is found in every cell, where it helps turn glucose into energy. Antioxidants are substances that work by attacking "free radicals," waste products created when the body turns food into energy. Free radicals cause harmful chemical reactions that can damage cells in the body, making it harder for the body to fight off infections and resulting in damage to organs and tissues.

Alpha-lipoic acid is unique in several ways. Unlike other antioxidants, which work only in water (such as vitamin C) or fatty tissues (such as vitamin E), alpha-lipoic acid is both fat- and water-soluble. That means it can work throughout the body. In addition, antioxidants are depleted as they attack free radicals, but evidence suggests alpha-lipoic acid may help to regenerate these other antioxidants and make them active again.

In the cells of the body, alpha-lipoic acid is converted into dihydrolipoic acid. Alpha-lipoic acid is not the same as alpha linolenic acid, which is an omega-3 fatty acid (see "Alpha linolenic acid") that may help heart health. Confusion can arise because both are sometimes abbreviated Alpha-lipoic acid.

Diabetes

Alpha-lipoic acid can lower blood sugar levels, and its ability to kill free radicals may help reduce pain, burning, itching, tingling, and numbness in people who have nerve damage caused by diabetes (called peripheral neuropathy). Alpha-lipoic acid has been used for years for this purpose in Europe, and at least one study found that intravenous (IV) doses of alpha-lipoic acid helped reduce symptoms. However, the evidence indicating that taking alpha-lipoic acid orally will help is weaker; most studies have been small and poorly designed. One 2006 study did show benefit from taking alpha-lipoic acid for diabetic neuropathy compared to placebo.

Taking alpha-lipoic acid does appear to help another diabetes-related condition, called autonomic neuropathy, which affects the nerves supplying the heart. One study found that 73 people with autonomic neuropathy improved when taking 800 mg of alpha-lipoic acid orally compared to placebo.

Liver Disease

Alpha-lipoic acid has been proposed as a treatment for alcohol-related liver disease, but so far there is no evidence that it works. {actually, there is, but this article is "mainstream" and thus not on the cutting edge.} Alpha-lipoic acid has been administered by IV along with silymarin to treat people who have eaten the poisonous mushroom Amanita, which causes liver damage.

Brain Function and Stroke

Because alpha-lipoic acid can pass easily into the brain, it has protective effects on brain and nerve tissue and is being investigated as a treatment for stroke and other brain disorders involving free radical damage. Animals treated with alpha-lipoic acid, for example, suffered less brain damage and had a four times greater survival rate after a stroke than animals who did not receive this supplement. But more research is needed to understand whether this benefit applies to people as well.

Other

Some preliminary studies suggest alpha-lipoic acid may be helpful in treating glaucoma, but there is not enough evidence to say for sure whether it is beneficial. In test tubes, alpha-lipoic acid appears to inhibit growth of the HIV virus, but it isn't known whether the supplement would have the same effect in people.

Precautions:

Because of the potential for side effects and interactions with medications, dietary supplements should be taken only under the supervision of a health care provider.

No evidence suggests whether or not alpha-lipoic acid is safe for women who are pregnant or breastfeeding, so such women should not take alpha-lipoic acid.

Side effects are generally rare and may include skin rash.

Alpha-lipoic acid can lower blood sugar levels, so people with diabetes should take alpha-lipoic acid only under the supervision of their doctor. (See "Interactions" below.)

Results of animal studies suggest that people who are deficient in thiamine (vitamin B1), a condition often associated with alcoholism, should not take alpha-lipoic acid.

Possible Interactions:

If you are currently being treated with any of the following medications, you should not use alpha-lipoic acid without first talking to your health-care provider.

Insulin and drugs that lower blood sugar -- Apha-lipoic acid can combine with these drugs to further reduce blood sugar levels, resulting in hypoglycemia (low blood sugar). Tell your doctor before taking alpha-lipoic acid and monitor your blood sugar levels closely; your doctor may need to adjust your medication doses.

Thyroid-regulating medications, Levothyroxine -- Apha-lipoic acid may lower levels of thyroid hormone. Blood hormone levels and thyroid function tests should be monitored closely in people taking thyroid hormones who are also taking alpha-lipoic acid.
http://www.the-natural-path.com/alpha-lipoic-acid.html

Alpha Lipoic Acid and Other Treatments for Alzheimer's Disease

Recent research studies have shown that certain nutrients and supplements, such as alpha lipoic acid (ALA), can slow down or even reverse Alzheimer's disease. While a cure has yet to be found, the results are extremely encouraging.

Alpha Lipoic Acid

New research has identified ALA as a critical nutrient in the treatment of Alzheimer’s disease. For example, one study found that alpha lipoic acid protects against Alzheimer’s by preventing oxidative stress and free radical production. In this study 600 milligrams of alpha lipoic acid was given daily to patients with Alzheimer’s disease for roughly a year, helping to stabilize the condition. Alpha lipoic acid and vitamin E work synergistically to prevent free radical damage to brain cells during strokes according to new research. Therefore, take daily supplements of 300 – 600 IU of natural vitamin E, in conjunction with alpha lipoic acid. I recommend you consider Natural Vitamin E. Take one capsule per day.
http://www.chiro.org/nutrition/Alpha_Lipoic_Acid.shtml
{Several good articles linked from the above page}
 

dantem

The Living Force
FOTCM Member
Laura said:
I just read "The Alpha Lipoic Acid Breakthrough" and want to recommend the book and the supplement!

Precautions:

Because of the potential for side effects and interactions with medications, dietary supplements should be taken only under the supervision of a health care provider.

No evidence suggests whether or not alpha-lipoic acid is safe for women who are pregnant or breastfeeding, so such women should not take alpha-lipoic acid.

Side effects are generally rare and may include skin rash.

Alpha-lipoic acid can lower blood sugar levels, so people with diabetes should take alpha-lipoic acid only under the supervision of their doctor. (See "Interactions" below.)

Results of animal studies suggest that people who are deficient in thiamine (vitamin B1), a condition often associated with alcoholism, should not take alpha-lipoic acid.

Possible Interactions:

If you are currently being treated with any of the following medications, you should not use alpha-lipoic acid without first talking to your health-care provider.

Insulin and drugs that lower blood sugar -- Apha-lipoic acid can combine with these drugs to further reduce blood sugar levels, resulting in hypoglycemia (low blood sugar). Tell your doctor before taking alpha-lipoic acid and monitor your blood sugar levels closely; your doctor may need to adjust your medication doses.

Thyroid-regulating medications, Levothyroxine -- Apha-lipoic acid may lower levels of thyroid hormone. Blood hormone levels and thyroid function tests should be monitored closely in people taking thyroid hormones who are also taking alpha-lipoic acid.
http://www.chiro.org/nutrition/Alpha_Lipoic_Acid.shtml
{Several good articles linked from the above page}


Thanks for the Precautions part!

I'm just at page 245 of Blaylok's 'Exitotoxins', where he tells us:

...One of the more interesting and vitally important characteristics of DHLA (Reduced alpha-lipoic acid) is that apperas to be able to regenerate other antioxidants. As mentioned before, when vitamin C and E are used to neutralize free radicals they themselves become oxidized. To be used as antioxidants, they must be returned to a reduced form. DHLA is a powerful regenerator of reduced ascorbate and tocopherol. It is their continuous process of recycling of vitamin C and E to their reduced form by DHLA that prevents the cell membrane from undergoing destructive lipid peroxidation... Alpha-lipoic acid is also known to increase the levels of ubiquinol (coenzyme Q10) during time of oxygen stress (free radical buildup)... increases intracellular glutathione... and glucose transport into cells as well, even without insulin... treating both type I and II diabetes (juvenile and adult onset)
The 'Exitotoxins' book is dealing mostly with brain metabolism here.

This last part seems to contradict or complement the above:

Insulin and drugs that lower blood sugar -- Apha-lipoic acid can combine with these drugs to further reduce blood sugar levels, resulting in hypoglycemia (low blood sugar). Tell your doctor before taking alpha-lipoic acid and monitor your blood sugar levels closely; your doctor may need to adjust your medication doses.
But I need a doctor to clear that one :)
 

Niall

SuperModerator
Moderator
FOTCM Member
Sott carried this article from Dr. Mercola on the benefits of ALA in May:

Alpha Lipoic Acid: The Antioxidant That Can Smash Insulin Resistance and Autoimmune Disease

Why You Need Antioxidants

Your entire body, including your DNA, is under endless, daily assault from a variety of sources, from poor diets to pollution. Think of your cells, including your brain cells, each getting hit by free-radicals thousands of times a day. This violent process is called "oxidation," which damages your cells.

Enter antioxidants. They include vitamins and other nutrients that target free radicals.

Food, particularly fruits and vegetables, is a powerful source of these valiant protectors, and your body produces some itself. Their role is to limit the damage to your cells, which can slow down disease and signs of aging.

In the case of alpha lipoic acid, your body does produce it in minute quantities, but most of it comes from your diet. Some of the best natural sources include grass-fed red meat and organ meats.
Which, if you're following the UltraDiet, you're not going to be receiving much of.

The Benefits of Alpha Lipoic Acid

Alpha lipoic acid (ALA) has many functions, but it's one of the most effective free radical scavengers, and the only one known to easily get into your brain.

It also has the ability to regenerate other antioxidants such as vitamins C, E, and glutathione. So, when your body has used up these antioxidants, if there's ALA around, it helps regenerate them.

You may not know this, but glutathione is another very important antioxidant. You can get it from supplements, but the only form that works effectively is the reduced form, which is difficult to absorb when taken orally. It is much more cost effective to supplement with precursors, or items like alpha lipoic acid that regenerates glutathione.

Alpha lipoic acid also recycles coenzyme Q10 and NAD (nicotinamide adenine dinucleotide).

But, if that wasn't enough, this powerful antioxidant is also:

* A great modifier of gene expression to reduce inflammation
* A very potent heavy metal chelator

* An enhancer of insulin sensitivity

The benefits of ALA can appear near miraculous. For example, according to Dr. Berkson, Russia has successfully used ALA intravenously to reverse ischemia reperfusion injuries by injecting it right after a heart attack or a stroke.

And people with diabetes or metabolic syndrome tend to do much better when taking lipoic acid, as it enhances insulin sensitivity.

There's even been quite a bit of research showing it can restore T cell function. T cells are a type of white blood cells that are of key importance to your immune system, and are at the core of adaptive immunity, the system that tailors your body's immune response to specific pathogens.
 

Helle

Jedi Master
Finally found a place that sells this in Holland. Hurrah for internetshopping! Not cheap though, but from what I can read in the articles, 1 pill a day (400mg) should be enough for one as me, with no diabetes or any other illness at all.


Thanks for the very informative links.
 

adam7117

Jedi Master
FOTCM Member
Laura said:
I just read "The Alpha Lipoic Acid Breakthrough" and want to recommend the book and the supplement! The author isn't pushing anything, not even his own "plan" so you won't find any recommendations other than very sensible ones that fit well with all we have already learned about diet and detoxing. What is important about this book is the clear way he describes several bio-chemical systems of the body so that anyone can understand what is going on especially in respect of the damage that toxicity can do to your body at the DNA level, and how to ameliorate this.
I've gotta say - this supplement is very impressive and works for me. I now jokingly refer to ALA as "my superhero pills".

Having struggled with health problems in the last couple of years, every bit helps. Of course, to really push the body in the right direction, I had to work on the diet, have a few tests done and talk to a doc or three. Once coffee, wheat and dairy were gone from my system, I began to be daring with the more interesting supplements.

This is the first one I tried (not counting melatonin) - on top of the standard mineral mix. It's most fabulous! Since I was severely depleted all around, it's work in progress although one with more ups than downs. The "springiness" in the muscles, improved mental clarity - and getting up refreshed are unmistakeable.

I take 200mg in the morning (with spirulina and minerals) and 200mg before bed. I find that this bedtime dose helps me wake up easier in the morning.

To that, I add 12mg of melatonin a day - 6mg in the morning and 6mg before bed. Although, I have been doing this for years and found that amount to be optimal.

Anywhoo, ALA is staying on my breakfast menu. :cool2:
 

Helle

Jedi Master
Since I have no symptoms or pains or aches anywhere, I don't know if I would be able to tell any difference in taking ALA, but I can certainly read about the benefits, so why not add it to my daily routine. :)
 

Gaby

SuperModerator
Moderator
FOTCM Member
Here is another article, it is more "mainstream", but still some good info and further links (check the original link to see them):

http://lpi.oregonstate.edu/infocenter/othernuts/la/

Summary

* Alpha-lipoic acid (LA), also known as thioctic acid, is a naturally occurring compound that is synthesized in small amounts by humans. More information
* Endogenously synthesized LA is bound to protein and functions as a cofactor for several important mitochondrial enzymes. More information
* Supplementation with high doses of LA transiently increases plasma and cellular levels of free LA. More information
* Although LA is a potent antioxidant in the test tube, LA supplementation may affect health by stimulating glutathione synthesis, enhancing insulin signaling and modulating the activity of other cell signaling molecules and transcription factors. More information
* Overall, the available research indicates that treatment with 600 mg/day of intravenous racemic LA for 3 weeks significantly reduces the symptoms of diabetic peripheral neuropathy. More information
* Although the benefit of long-term oral LA supplementation for diabetic peripheral neuropathy is less clear, there is some evidence that oral supplementation with at least 600 mg/day of racemic LA may be beneficial. More information
* It is not yet known whether LA supplementation is beneficial in the treatment of multiple sclerosis or neurodegenerative diseases, such as Alzheimer’s disease. More information
* If you choose to take LA supplements, the Linus Pauling Institute recommends a daily dose of 200-400 mg/day of racemic LA for generally healthy people.

Introduction

Alpha-lipoic acid (LA), also known as thioctic acid, is a naturally occurring compound that is synthesized in small amounts by plants and animals, including humans (1, 2). Endogenously synthesized LA is covalently bound to specific proteins, which function as cofactors for several important mitochondrial enzyme complexes (see Biological Activities below). In addition to the physiological functions of protein-bound LA, there is increasing scientific and medical interest in potential therapeutic uses of pharmacological doses of free LA (3). LA contains two thiol (sulfur) groups, which may be oxidized or reduced (Figure). The reduced form is known as dihydrolipoic acid (DHLA), while the oxidized form is known as LA (4). LA also contains an asymmetric carbon, meaning there are two possible optical isomers that are mirror images of each other (R-LA and S-LA). Only the R- isomer is endogenously synthesized and bound to protein. Free LA supplements may contain either R-LA or a 50/50 (racemic) mixture of R-LA and S-LA (see Supplements below).

Metabolism and Bioavailability

Endogenous Biosynthesis

LA is synthesized de novo from an 8-carbon fatty acid (octanoic acid) in mitochondria, where protein-bound LA functions as an enzyme cofactor. Recent evidence suggests that LA can be synthesized “on site” from octanoic acid that is already covalently bound to LA-dependent enzymes (5, 6). The final step in LA synthesis is the insertion of two sulfur atoms into octanoic acid. This reaction is catalyzed by lipoyl synthase, an enzyme that contains iron-sulfur clusters, which are thought to act as sulfur donors to LA (7, 8). The gene for lipoyl synthase has recently been cloned, and research is underway to learn more about its regulation (9).

Dietary and Supplemental Alpha-Lipoic Acid

Exogenous LA from the diet can be activated with ATP or GTP by lipoate activating enzyme, and transferred to LA-dependent enzymes by lipoyl transferase (10, 11). Consumption of LA from foods has not yet been found to result in detectable increases of free LA in human plasma or cells (3, 12). In contrast, high oral doses of free LA (50 mg or more) result in significant but transient increases in free LA in plasma and cells. Pharmacokinetic studies in humans have found that about 30-40% of an oral dose of racemic LA is absorbed (12, 13). Oral LA supplements are better absorbed on an empty stomach than with food. Taking racemic LA with food decreased peak plasma LA concentrations by about 30% and total plasma LA concentrations by about 20% compared to fasting (14). After oral dosing with racemic LA, peak plasma concentrations of R-LA were found to be 40-50% higher than S-LA, suggesting R-LA is better absorbed than S-LA (12, 14, 15). Both isomers are rapidly metabolized and excreted. Plasma LA concentrations generally peak in one hour or less and decline rapidly (12, 13, 15, 16). In cells, LA is quickly reduced to DHLA, and studies in vitro indicate that DHLA is rapidly exported from cells (3).

Biological Activities

Protein-Bound Alpha-Lipoic Acid

Enzyme Cofactor

R-LA is an essential cofactor for several mitochondrial enzyme complexes that catalyze critical reactions related to energy production and the catabolism (breakdown) of alpha-keto acids and amino acids (17). In each case, R-LA is covalently bound to a specific lysine residue in one of the proteins in the enzyme complex. The pyruvate dehydrogenase complex catalyzes the conversion of pyruvate to acetyl-coenzyme A (CoA), an important substrate for energy production via the citric acid cycle. The alpha-ketoglutarate dehydrogenase complex catalyzes the conversion of alpha-ketoglutarate to succinyl CoA, another important citric acid cycle intermediate. The activity of the branched-chain ketoacid dehydrogenase complex results in the catabolism of the branched-chain amino acids, leucine, isoleucine and valine (18). The glycine cleavage system is a multi-enzyme complex that catalyzes the oxidation of glycine to form 5,10 methylene tetrahydrofolate, an important cofactor in nucleic acid synthesis (19).

Free Alpha-Lipoic Acid

When considering the biological activities of supplemental free LA, it is important to keep in mind the limited and transient nature of the increases in plasma and tissue LA (see Metabolism and Bioavailability above) (3).

Antioxidant Activities

Scavenging Reactive Oxygen and Nitrogen Species: Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are highly reactive compounds with the potential to damage DNA, proteins and lipids (fats) in cell membranes. Both LA and DHLA can directly scavenge (neutralize) physiologically relevant ROS and RNS in the test tube [reviewed in (3)]. However, it is not clear whether LA acts directly to scavenge ROS and RNS in vivo. The highest tissue concentrations of free LA likely to be achieved through oral supplementation are at least 10 times lower than those of other intracellular antioxidants, such as vitamin C and glutathione. Moreover, free LA is rapidly eliminated from cells, so any increases in direct radical scavenging activity are unlikely to be sustained.

Regeneration of Other Antioxidants: When an antioxidant scavenges a free radical, it becomes oxidized itself and is not able to scavenge additional ROS or RNS until it has been reduced. DHLA is a potent reducing agent with the capacity to reduce the oxidized forms of several important antioxidants, including vitamin C and glutathione (20). DHLA may also reduce the oxidized form of alpha-tocopherol (the alpha-tocopheroxyl radical) directly or indirectly, by reducing the oxidized form of vitamin C (dehydroascorbate), which is able to reduce the alpha-tocopheroxyl radical (21). Coenzyme Q10 is an important component of the mitochondrial electron transport chain that also has antioxidant activity. DHLA can also reduce oxidized forms of coenzyme Q10 (22), which may also reduce the alpha-tocopheroxyl radical (23). Although DHLA has been found to regenerate oxidized antioxidants in the test tube, it is not known whether DHLA effectively regenerates other antioxidants under physiological conditions (3).

Metal Chelation: Redox-active metal ions, such as free iron and copper, can induce oxidative damage by catalyzing reactions that generate highly reactive free radicals (24). Compounds that chelate (bind) free metal ions in a way that prevents them from generating free radicals offer promise in the treatment of neurodegenerative and other chronic diseases, in which metal-induced oxidative damage may play a role (25). Both LA and DHLA have been found to inhibit copper- and iron-mediated oxidative damage in the test tube (26, 27), and to inhibit excess iron and copper accumulation in animal models (28, 29).

Induction of Glutathione Synthesis: Glutathione is an important intracellular antioxidant that also plays a role in the detoxification and elimination of potential carcinogens and toxins. Studies in animals have found that glutathione synthesis and tissue glutathione levels are significantly lower in aged animals than in younger animals, leading to decreased ability of aged animals to respond to oxidative stress or toxin exposure (30). LA has been found to increase glutathione synthesis in cultured cells and in the tissues of aged animals fed LA. Recent research suggests that LA may increase glutathione synthesis in aged animals by increasing the expression of gamma-glutamylcysteine ligase (GCL), the rate-limiting enzyme in glutathione synthesis (31) and by increasing cellular uptake of cysteine, an amino acid required for glutathione synthesis (32).

Modulating Signal Transduction

Insulin Signaling: The binding of insulin to the insulin receptor (IR) triggers the autophosporylation of several tyrosine residues on the IR. Activation of the IR in this manner stimulates a cascade of protein phosphorylations, resulting in the translocation of glucose transporters (GLUT4) to the cell membrane and increased cellular glucose uptake (3, 33). LA has been found to increase GLUT4 translocation to cell membranes and to increase glucose uptake in cultured adipose (fat) and muscle cells (34, 35). Although LA does not appear to bind to the IR like insulin, it can activate the insulin signaling cascade in cultured cells, possibly by acting as a mild oxidizing agent (3, 33).

PKB/Akt-dependent Signaling: In addition to insulin signaling, phosphorylation and dephosphorylation of other cell signaling molecules affect a variety of cellular processes, including metabolism, stress responses, proliferation and survival (3). One such molecule is protein kinase B also known as Akt (PKB/Akt). The addition of LA to cultured cells has been found to activate PKB/Akt-dependent signaling resulting in increased survival of neurons (36). LA administration improved nitric oxide-dependent vasodilation in aged rats by increasing PKB/Akt-dependent phosphorylation of endothelial nitric oxide synthase (eNOS), which increases eNOS catalyzed production of nitric oxide (37).

Redox-Sensitive Transcription Factors: Transcription factors are proteins that bind to specific sequences of DNA and promote or repress the transcription of selected genes. Some transcription factors are sequestered outside the nucleus until some sort of signal induces their translocation to the nucleus. Oxidative stress or changes in the balance between oxidation and reduction (redox status) in a cell can trigger the translocation of redox-sensitive transcription factors to the nucleus. One such family of redox-sensitive transcription factors, known as nuclear factor-kappa B (NF-KB), regulates a number of genes related to inflammation and cell cycle control, which are involved in the pathology of diabetes, atherosclerosis and cancer (19). Physiologically relevant concentrations of LA added to cultured cells have been found to inhibit NF-KB nuclear translocation (38). Another redox-sensitive transcription factor known as Nrf2 enhances the transcription of genes that contain specific DNA sequences known as antioxidant response elements (AREs). LA has been found to enhance the nuclear translocation of Nrf2 and the transcription of genes containing AREs in vivo, including genes for GCL, the rate-limiting enzyme in glutathione synthesis (31).

Deficiency

LA deficiency has not been described, suggesting that humans are able to synthesize enough to meet their needs for enzyme cofactors (39).

Disease Treatment

Diabetes Mellitus

Chronically elevated blood glucose levels are the hallmark of diabetes mellitus (DM). In type 1 DM, insulin production is insufficient due to autoimmune destruction of the insulin-producing beta-cells of the pancreas. Type 1 DM is also known as insulin-dependent DM, because exogenous insulin is required to maintain normal blood glucose levels. In contrast, impaired cellular glucose uptake in response to insulin (insulin resistance) plays a key role in the development of type 2 DM (40). Although individuals with type 2 DM may eventually require insulin, type 2 DM is also known as noninsulin-dependent DM because interventions that enhance insulin sensitivity may be used to maintain normal blood glucose levels.

Glucose Utilization

There is limited evidence that high doses of LA can improve glucose utilization in individuals with type 2 DM. A small clinical trial in 13 patients with type 2 DM found that a single intravenous infusion of 1000 mg of racemic LA improved insulin-stimulated glucose disposal (insulin sensitivity) by 50% compared to a placebo infusion (41). In an uncontrolled pilot study of 20 patients with type 2 DM, intravenous infusion of 500 mg/day of racemic LA for 10 days also improved insulin sensitivity measured 24 hours after the last infusion (42). A placebo-controlled study of 72 patients with type 2 DM found that oral administration of racemic LA at doses of 600 mg/day, 1200 mg/day or 1800 mg/day improved insulin sensitivity by 25% after 4 weeks of treatment (43). There were no significant differences among the three doses of LA, suggesting that 600 mg/day may be the maximum effective dose (40). Data from animal studies suggests that the R-isomer of LA may be more effective in improving insulin sensitivity than the S-isomer (35, 44), but this possibility has not been tested in any published human trials.

The effect of LA supplementation on long-term blood glucose (glycemic) control has not been well-studied. In an uncontrolled pilot study of a controlled-release form of oral racemic LA, 15 patients with type 2 DM took 900 mg/day for 6 weeks and 1200 mg/day for another 6 weeks in addition to their current medications (16). At the end of 12 weeks, plasma fructosamine concentrations decreased by about 10%, but glycosylated hemoglobin (HbA1c) levels did not change. Plasma fructosamine levels reflect blood glucose control over the past 2-3 weeks, while HbA1c values reflect blood glucose control over the past 2-4 months. At present, it is not clear whether oral or intravenous LA therapy improves long-term glycemic control in individuals with type 2 DM.

Vascular Disease

The inner lining of blood vessels, known as the endothelium, plays an important role in preventing vascular disease. Endothelial function is often impaired in diabetic patients, who are at high risk for vascular disease (45). Intra-arterial infusion of racemic LA improved endothelium-dependent vasodilation in 39 diabetic patients, but not in 11 healthy controls (46). Endothelial function can be assessed noninvasively by using ultrasound to measure flow-mediated vasodilation, which is endothelium-dependent (47). A randomized controlled trial assessed the effect of oral LA supplementation on flow-mediated vasodilation in 58 patients diagnosed with the metabolic syndrome, a condition of abnormal glucose and lipid (fat) metabolism (48). Oral supplementation with 300 mg/day of LA for 4 weeks improved flow-mediated vasodilation by 44% compared to placebo. Diabetic patients are also at high risk of microvascular disease, which may contribute to diabetic neuropathy (40). In an uncontrolled study, oral supplementation with 1200 mg/day of racemic LA for 6 weeks improved a measure of capillary perfusion in the fingers of 8 diabetic patients with peripheral neuropathy (49). While these results are encouraging, long-term randomized controlled trials are needed to determine whether LA supplementation can reduce the risk of vascular complications in individuals with diabetes.

Diabetic Neuropathy

Intravenous and oral LA are approved for the treatment of diabetic neuropathy in Germany (4). More than 20% of diabetic patients develop peripheral neuropathy, a type of nerve damage that may result in pain, loss of sensation and weakness, particularly in the lower extremities (40). In addition to the pain and disability caused by diabetic neuropathy, it is a leading cause of lower limb amputation in diabetic patients (50). The results of several large randomized controlled trials indicate that maintaining blood glucose at near normal levels is the most important step in decreasing the risk of diabetic neuropathy (51, 52). However, such intensive blood glucose control may not be achievable in all diabetic patients. A meta-analysis that combined the results of four randomized controlled trials, including 1258 diabetic patients, found that treatment with 600 mg/day of intravenous racemic LA for 3 weeks significantly reduced the symptoms of diabetic neuropathy to a clinically meaningful degree (53).

The efficacy of oral LA in the treatment of diabetic neuropathy is less clear. A short-term study of 24 patients with type 2 DM found that the symptoms of peripheral neuropathy were improved in those who took 1800 mg/day of oral racemic LA for 3 weeks compared to those who took a placebo (54). A much larger clinical trial randomly assigned more than 500 patients with type 2 DM and symptomatic peripheral neuropathy to one of the following treatments: 1) 600 mg/day of intravenous racemic LA for 3 weeks followed by 1800 mg/day of oral racemic LA for 6 months, 2) 600 mg/day of intravenous racemic LA for 3 weeks followed by oral placebo for 6 months, or 3) intravenous placebo for 3 weeks followed by oral placebo for 6 months (55). Although symptom scores did not differ significantly from baseline in any of the groups, assessments of sensory and motor deficits by physicians improved significantly after 3 weeks of intravenous LA therapy. Motor and sensory deficits were also somewhat improved at the end of 6 months of oral LA therapy, but the trend did not reach statistical significance. In the longest controlled trial of oral LA therapy, 299 patients with diabetic peripheral neuropathy were randomly assigned to treatment with 1200 mg/day of racemic LA, 600 mg/day of racemic LA or a placebo (56). However, after 2 years of treatment, only 65 of the original participants were included in the final analysis. In that subgroup, those who took either 1200 mg/day or 600 mg/day of LA showed significant improvement in electrophysiological tests of nerve conduction compared to those who took the placebo.

Another neuropathic complication of diabetes is cardiovascular autonomic neuropathy, which occurs in as many as 25% of diabetic patients (40). Cardiovascular autonomic neuropathy is characterized by reduced heart rate variability, and is associated with increased risk of mortality in diabetic patients. In a randomized controlled trial of 72 patients with type 2 DM and reduced heart rate variability, oral supplementation with 800 mg/day of racemic LA for 4 months resulted in significant improvement in 2 out of 4 measures of heart rate variability compared to placebo (57).

Overall, the available research suggests that treatment with 600 mg/day of intravenous LA for 3 weeks significantly reduces the symptoms of diabetic peripheral neuropathy. Although the benefit of long-term oral LA supplementation is less clear, there is some evidence to suggest that oral LA may be beneficial in the treatment of diabetic peripheral neuropathy (600-1800 mg/day) and cardiovascular autonomic neuropathy (800 mg/day).

Multiple Sclerosis

Feeding high doses of LA to mice with experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS), has been found to slow disease progression (58, 59). In these animals, LA feeding appeared to inhibit the migration of inflammatory T cells into the brain and spinal cord, possibly by inhibiting the activity of an enzyme known as matrix metalloproteinase (MMP)-9. A small pilot study designed to evaluate the safety of LA in 30 people with relapsing or progressive MS found that treatment with 1200-2400 mg/day of oral LA for 2 weeks was generally well-tolerated (see Safety), and that higher peak serum levels of LA were associated with greater decreases in serum MMP-9 levels (60). However, this pilot study was not designed to assess the clinical benefit of LA. Larger, long-term clinical trials are needed to assess the safety and efficacy of LA in the treatment of MS (61).

Cognitive Decline and Dementia

LA alone or in combination with other antioxidants or L-carnitine has been found to improve measures of memory in animal models of age-associated cognitive decline, including rats (62, 63), mice (64) and dogs (65). However, it is not clear whether oral LA supplementation can slow cognitive decline related to aging or other pathology in humans. An uncontrolled, open-label trial in 9 patients with Alzheimer’s disease and related dementias, who were also taking acetylcholinesterase inhibitors, reported that oral supplementation with 600 mg/day of racemic LA appeared to stabilize cognitive function over a one-year period (66). However, the significance of these findings is difficult to assess without a control group for comparison. A randomized controlled trial found that oral supplementation with 1200 mg/day of racemic LA for 10 weeks was of no benefit in treating HIV-associated cognitive impairment (67). Although studies in animals suggest that LA may be helpful in slowing age-related cognitive decline, randomized controlled trials are needed to determine whether LA supplementation is effective in preventing or slowing cognitive decline associated with age or neurodegenerative disease.

Sources

Endogenous Biosynthesis

R-LA is synthesized endogenously by humans and bound to proteins (see Metabolism and Bioavailability above).

Food Sources

R-LA occurs naturally in foods covalently bound to lysine in proteins (lipoyllysine). Although LA is found in a wide variety of foods from plant and animal sources, quantitative information on the LA or lipoyllysine content of food is limited and published databases are lacking. Animal tissues that are rich in lipoyllysine (~1-3 mcg/g dry wt) include kidney, heart and liver, while edible plants that are rich in lipoyllysine include spinach and broccoli (68). Somewhat lower amounts of lipoyllysine (~0.5 mcg/g dry wt) have been measured in tomatoes, peas and Brussels sprouts.

Supplements

Unlike LA in foods, LA in supplements is free, meaning it is not bound to protein. Moreover, the amounts of LA available in dietary supplements (200-600 mg) are likely as much as 1000 times greater than the amounts that could be obtained in the diet. In Germany, LA is approved for the treatment of diabetic neuropathies and is available by prescription (39). LA is available as a dietary supplement without a prescription in the US (69). Most LA supplements contain a racemic (50/50) mixture of R-LA and S-LA (d,l-LA). Supplements that claim to contain only R-LA are usually more expensive, and information regarding their purity is not currently available (70). Since taking LA with a meal decreases its bioavailability, it is generally recommended that LA be taken on an empty stomach (one hour before or two hours after eating).

Racemic vs. R-LA Supplements

R-LA is the isomer that is synthesized by plants and animals and functions as a cofactor for mitochondrial enzymes in its protein bound form (see Biological Activities). Direct comparisons of the bioavailability of oral racemic LA and R-LA supplements have not been published. After oral dosing with racemic LA, peak plasma concentrations of R-LA were found to be 40-50% higher than S-LA, suggesting R-LA is better absorbed than S-LA, but both isomers are rapidly metabolized and eliminated (12, 14, 15). In rats, R-LA was more effective than S-LA in enhancing insulin-stimulated glucose transport and metabolism in skeletal muscle (44), and R-LA was more effective than racemic LA and S-LA in preventing cataracts (71). However, virtually all of the published studies of LA supplementation in humans have used racemic LA. At present, it is not clear whether R-LA supplements are more effective than racemic LA supplements in humans.

Safety

Adverse Effects

In general, LA supplementation has been found to have few serious side effects. Intravenous administration of racemic LA at doses of 600 mg/day for 3 weeks (53) and oral racemic LA at doses as high as 1800 mg/day for 6 months (56) and 1200 mg/day for 2 years (55) did not result in serious adverse effects when used to treat diabetic peripheral neuropathy. Two minor anaphylactoid reactions and one severe anaphylactic reaction, including laryngospasm, were reported after intravenous LA administration (40). The most frequently reported side effects to oral LA supplementation are allergic reactions affecting the skin, including rashes, hives and itching. Gastrointestinal symptoms, including abdominal pain, nausea, vomiting and diarrhea have also been reported. Malodorous urine has also been noted by people taking 1200 mg/day of LA orally (60).

Pregnancy and Lactation

The safety of LA supplements in pregnant and lactating women has not been established.

Drug Interactions

Because there is some evidence that LA supplementation improves insulin-mediated glucose utilization (43), it is possible that LA supplementation could increase the risk of hypoglycemia in diabetic patients using insulin or oral antidiabetic agents. Consequently, blood glucose levels should be monitored closely when LA supplementation is added to diabetes treatment regimens. Co-administration of a single oral dose of racemic LA (600 mg) and the oral antidiabetic agents, glyburide or acarbose, did not result in any significant drug interactions in one study of 24 healthy volunteers (72).

Nutrient Interactions

Biotin

The chemical structure of biotin is similar to that of LA, and there is some evidence that high concentrations of LA can compete with biotin for transport across cell membranes (73). The administration of high doses of LA by injection to rats decreased the activity of two biotin-dependent enzymes by about 30-35% (74), but it is not known whether LA supplementation substantially increases the requirement for biotin in humans (75).

References
 

pete69

A Disturbance in the Force
I'm new to this forum. Just wanted to comment on the ALA, Laura, you should check out Bruce Ames (developer of the Ames test) and his work on the combination of Alpha lipoic acid and ALCAR (acetyl L-carnitine) another potent antioxidant, mitochondrial repair nutrient, as well as a great cognitive and sexual performance nutrient. The combination seems to have a synergistic effect and really reduces oxidative damage as well as being ultra important for liver detox by raising glutathione . There is also some good information in his Nutrigenomics organization.

Most of the research on ALA is from the R-ALA isomer, and there is some controversy over potential problems with regular ALA. I listened to your interview on the infrared sauna and interestingly enough I started taking ALA based on Sherry Rogers suggestion in "Detoxify or Die." I got into the detox thing years ago and even have one of those fold-up far infrared saunas that you sit in with your head sticking out.

Great forum with fantastic information.
 

gwb1995

Jedi
I came across another form of ALA on VRP's site today and am curious if it would not be a better source than just using ALA. The product is described as follows:

"Directly involved with healthy cell regeneration, R-Lipoic Acid is rightly called the ‘mitochondrial antioxidant’.* Lipoic acid is one of the most thoroughly investigated dietary supplements and most healthcare practitioners agree it is a preventive supplement of choice. R-Lipoic Acid is a more potent form – the more biologically active form – of alpha lipoic acid. As such, it offers more benefit with a lower dose. Lipoic acid serves to regenerate vitamins C and E, and helps maintain glutathione levels, a vital cellular antioxidant and liver protectant.* It is a vascular and neuroprotective agent.* It works throughout the body to support vascular integrity often compromised by elevated sugar and fats.* It also promotes eye health and strong immune function.*

I'm not a doctor, so I thought I would ask if anyone here has any thoughts.

Also from the tread on Swine Flu vaccines,

Psyche said:
LQB said:
Dr Blaylock maintains that the worst effects arise from a cytokine storm set off in the brain due to contaminant DNA/RNA, organisms, and viral proteins that lodge in the brain, produce lesions, and chronic brain inflammation. He said that independent studies showed that 60% of vaccine samples tested were positive for contamination. The adjuvants just make everything much worse.
Another couple of antioxidants that should come up very handy in case of vaccination is alpha lipoic acid (ALA) and n-acetylcysteine (NAC).

Alpha lipoic acid (ALA) is also an exc chelator and repairs DNA. ALA also is a safe source of glutathione. ALA recycles other antioxidants such as vit C, vit E, and glutathione. Glutathione may not reliably be augmented by oral supplementation because it cannot always pass over the mitochondrial membrane. Therefore, glutathione must be synthesized within the mitochondrion. Research has demonstrated that ALA and its metabolite DHLA provoke the cell to produce significantly higher levels of glutathione. One study reports that a little ALA could raise the levels of glutathione by 30 to 70%.

NAC (N-acetylcysteine) is also considered a source of glutathione, but what I found interesting when I was researching about brain tumors is that NAC shrinked gliomas (super evil brain tumors) even when gluthatione-blockers where given and its benefits where not really well understood. But after that there has been more research about NAC and its ability to repair DNA as well.
If taking R-Lipoic Acid were the better choice, would one still need to use the NAC as described above. I would think this to be true.

Thanks for any help on this,

gwb
 

Gaby

SuperModerator
Moderator
FOTCM Member
gwb said:
If taking R-Lipoic Acid were the better choice, would one still need to use the NAC as described above. I would think this to be true.

Thanks for any help on this,

gwb
In my opinion, if you are healthy, ALA is enough. You can have NAC in stock in case of sickness or detox.
 

Laurentien2

Dagobah Resident
Hello Helle,

In this thread
http://www.umm.edu/altmed/articles/alpha-lipoic-000285.htm
I found this info for daily dose if taken only as a antioxidant.


Adult

Alpha-lipoic acid can be purchased in doses of 30 - 100 mg tablets. There are no established recommended doses.

* General antioxidant support: 20 - 50 mg per day
* Diabetes and diabetic neuropathy: 800 mg per day in divided doses
Finally found a place that sells this in Holland. Hurrah for internetshopping! Not cheap though, but from what I can read in the articles, 1 pill a day (400mg) should be enough for one as me, with no diabetes or any other illness at all.
Since I have no symptoms or pains or aches anywhere, I don't know if I would be able to tell any difference in taking ALA, but I can certainly read about the benefits, so why not add it to my daily routine. Smiley
Maybe 400mg is to strong a dose if you don't suffer from diabetes.
 

gwb1995

Jedi
Psyche,

Thanks for your response. I was 'seeing' the R-ALP as the ad wanted me to see it, as the BEST. Just another reminder of my mechanical ways. Also, I confused the use of NAC with ALP as necessary for the best effect in all uses. I did not make the connection from the unique threads and just combined them into one meaning.

I have recently ordered the Ultra Simple Diet, and that is the focus for me right now. I am sure I will have more questions soon, and will ask before making assumptions in the future.

gwb
 

Helle

Jedi Master
Laurentien said:
Maybe 400mg is to strong a dose if you don't suffer from diabetes.
Yes I see
Will it hurt though? :shock:

The ALA i bought is a 400mg per pill.

As far as I can read, it says that Side effects are generally rare and may include skin rash.

I certainly get enough then !!
 

genero81

The Living Force
FOTCM Member
Insert Quote
Quote from: Laurentien
Maybe 400mg is to strong a dose if you don't suffer from diabetes.

Yes I see
Will it hurt though?


Should be no problem if you take it with food, and probably no problem even without food. ;)
 

Helle

Jedi Master
Just found out, that my ALA pills comes in a Gelatin capsule containing maltodextrin :/
Will it be ok to open to capsule, and pour out the content yathink?

Geez it's hard to avoid that MSG.
 
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