Alpha-lipoic Acid Ala
 

Alpha Lipoic Acid Introduction

Alpha lipoic acid is useful for a variety of conditions. It is effective as therapy for diabetes, cardiovascular disease, HIV, and is considered a metal chelator. It may be helpful for neurodegenerative disease and has some practicality in cataract and glaucoma treatment. Alpha lipoic acid was once thought to be an essential vitamin for humans and animals. It was then discovered that humans produced it endogenously. Therefore it is not an essential nutrient.

In nature, alpha lipoic acid exists in two entantiomers (forms): the ® or the (s) entantiomer. The ® is the natural and most active form. Supplements of alpha lipoic acid contain a 50/50 ratio of the two forms.[1]

Alpha lipoic acid is absorbed within the small intestine. The natural or ® form is more absorbed than the (s) form. In the body it is reduced to dihydrolipoic acid (DHLA), which works together with alpha lipoic acid.

The endogenous production of alpha lipoic acid serves as a cofactor for two reactions involved in energy production of the Kreb’s cycle. It is a cofactor for the enzymes pyruvate dehydrogenase and alpha ketoglutarate dehydrogenase. Each of these reactions is carried out in the mitochondria. It also enhances energy production by the mitochondria in various tissues throughout the body. Alpha lipoic acid also serves as a cofactor for the production of the branched chain amino acids leucine, isoleucine, and valine.

In the 1980’s, the high antioxidant potential of alpha lipoic acid was discovered. Endogenous production does not supply the body enough to give alpha lipoic acid its antioxidant activity, therefore supplementation is necessary for any effects past those of a cofactor in metabolic reactions. As an antioxidant, alpha lipoic acid scavenges free radicals. It works as a redox pair with DHLA, its reduced form, to fulfill this scavenging action. Both contain the ability to scavenge hydroxyl radicals, nitric oxide radicals, peroxynitrite, hydrogen peroxide, and hypochorite. Alpha lipoic acid alone can scavenge single oxygen; DHLA can scavenge superoxide and peroxyl reactive oxygen species. [2]

Alpha lipoic acid is considered among the universal antioxidants, because it is both water and lipid soluble. It is for this characteristic that alpha lipoic acid is beneficial for conditions that occur in the cellular environment, as well as inside the cell and cell membrane. Another point that makes alpha lipoic acid unique is that it can pass the blood brain barrier, allowing for its antioxidant capabilities to be utilized by the CNS.

Alpha lipoic acid also serves as an antioxidant-recycling molecule. It is involved in the regeneration of Glutathione, Coenzyme Q10, Vitamin C, Vitamin E, and Vitamin A. [3]

Alpha Lipoic Acid Food Sources

Alpha lipoic acid is found in both plant and animal sources. Its highest concentration is in red meat. It can also be found in potatoes, carrots, yams, and sweet potatoes. Interestingly, the amounts found in food are similar to the amounts produced endogenously by humans. The range in food sources varies from 10 - 100 mcg per serving. This is a very small amount compared to the amount found in a supplement, which typically ranges from 50 - 200 milligrams per serving.

Alpha Lipoic Acid Uses

Alpha lipoic acid has many reported uses. It therapeutic origin began in Europe for used pertaining to diabetic neuropathy and polyneuropathy caused by alcoholism. It is now widely used for diabetes, cardiovascular disease, heavy metal poisoning, HIV, and as an antidote to aminta mushroom poisoning. Alpha lipoic acid is gaining stature as agent for uses in Alzheimer's disease and other neurodegenerative conditions, as well as cataracts and glaucoma.

Alpha lipoic acid use in diabetes is well researched. It has been shown to protect against insulin resistance in Type II diabetes or NIDDM. [4] It is believed that oxidative stress may contribute to the development of insulin resistance. Alpha lipoic acid decreases oxidative stress by quenching free radicals. Alpha lipoic acid also increases glucose uptake by the skeletal muscle, assisting in the insulin response. Excess glucose and insulin resistance is also pathological for the development of many other diseases.

The characteristic of increased glucose uptake into skeletal muscles makes alpha lipoic acid extremely popular with athletes and bodybuilders alike. Alpha lipoic acid is often used as a “shuttle,” transporting certain dietary supplements, especially Creatine, into skeletal muscle. This delivery system is considered more effective in developing an increase of muscle mass, as opposed to taking supplements not containing alpha lipoic acid. More research is, however, necessary.

Alpha lipoic acid is very beneficial for individuals suffering from polyneuropathy as a result of diabetes. It has been well researched in animal and human studies. The antioxidant properties improve blood flow and oxygen delivery to the neurons. [5] In study, alpha lipoic acid has also been shown to improve neuropathy clinically, as well as improving the nerve conduction in diabetic patients. [6] Alpha lipoic acid has also been shown to lower blood pressure in diabetics with no other treatment.

The clinical symptoms of diabetic neuropathy include:

  • pain
  • burning
  • tingling
  • and numbness in the affected areas.

Supplementation with alpha lipoic acid has been very effective at significantly reducing these symptoms in most patients. [7] It has also reduced parathesias associated with the neuropathy.

Alpha lipoic acid has been proven to be very useful in cardiovascular disease treatments. Alpha lipoic acid is considered a protective antioxidant and helps to prevent the oxidation of LDL and proteins, which are implicated in the development of cardiovascular disease. [8] This is accomplished via its own antioxidant properties in both lipids and aqueous environments. Its ability to recycle other antioxidants that are protective against cardiovascular disease, such as Coenzyme Q10, Vitamins A, C, and E, and Glutathione, is an equally important characteristic in combating this condition.

Alpha lipoic acid is also protective against the development and progression of atherosclerosis. [9] It uses its antioxidant capabilities to suppress the development of advanced glycation end products (AGE). These AGEs develop due to oxidative stressors and signal molecules that result in the beginning stages of clot formation. Without the initial assault, atherosclerosis is prevented.

Alpha lipoic acid also has benefits for cardiovascular disease following an ischemic event, such as stroke or myocardial infarction (heart attack). In animal studies it was shown to prevent damage caused by reperfusion. [10] When tissue in the heart or brain is without oxygen, the tissue area often suffers from ischemia. When blood flow and oxygen is restored, a reperfusion injury results that is often worse than the ischemic damage. In the body, alpha lipoic acid results in less lactic acid buildup and better mechanical recovery. It also decreases lipid peroxidation from free radicals after an ischemic event.

Alpha lipoic acid has been shown to inhibit the replication of HIV in vitro and is effective at increasing the number of T helper cells. Alpha lipoic acid utilizes it antioxidant capabilities to decrease reactive oxygen species that are responsible for activating NF-kappa B. [11] NF-kappa B is the signaling molecule inside T helper cells that begins transcription of the HIV genome. By inhibiting NF-kappa B, replication of the virus in indirectly inhibited. [12]

Alpha lipoic acid is a potent metal chelator. [13] The most pronounced chelation is that of copper. This makes alpha lipoic acid extremely useful for Wilson’s disease. Wilson’s disease is one of copper excess. Excessive copper is neurotoxic via the production of free radicals inside the brain. Administration of alpha lipoic acid to individuals with Wilson’s disease has resulted in decreased oxidative damage and decreased neuronal cell death. [14]

Alpha lipoic acid is also able to chelate the toxic metals mercury and cadmium. Mercury is the 2nd most common metal toxicity, caused by the high levels in fish and mercury dental amalgams. Alpha lipoic acid serves as an antioxidant and mercury chelator, protecting against neurological and renal damage caused by mercury. [15] It is also protective against the neurological damage and symptoms caused by cadmium poisoning. [16]

Alpha lipoic acid is beneficial for cataracts due to its antioxidant recycling capabilities. Cataracts are often due to a decrease in glutathione, resulting in an increase of cellular damage from free radicals. This oxidative damage is typically higher in the eyes because of the levels of UV light they are exposed to every day. Alpha lipoic acid regenerates glutathione and also quenches free radicals to aid in the prevention of cataracts. [17] It may also be beneficial for those suffering from glaucoma.

More recently, alpha lipoic acid has been studied as a possible treatment for neurodegenerative disorders. It has been successful in reversing a pyruvate dehydrogenase deficiency in patients with vascular dementia, as well as diminishing other symptoms in these individuals. [18] More research is being carried out to test alpha lipoic acid’s efficacy in Alzheimer’s disease, Parkinson’s disease, and Huntington’s.

Alpha Lipoic Acid Dosages

There is no established daily value or adequate intake for alpha lipoic acid. The amounts needed for normal physiologic functioning are produced endogenously by humans. An tolerable upper limit intake has also not been established.

The usual therapeutic dosage of alpha lipoic acid is 600 miiligrams (mg) per day. It has been used in much higher doses for therapeutic benefit without side effect. A normal preventative or maintenance dose is 50 - 100 mg/day for antioxidant protection.

The use of alpha lipoic acid in women who are pregnant or lactating is contraindicated.

Caution is also warranted in diabetic patients on hypoglycemic medications because of alpha lipoic acid’s blood sugar lowering capabilities. There is also potential for hypoglycemia to develop. Blood sugar should be regularly monitored and medications adjusted when alpha lipoic acid is used as a treatment. [19]

Alpha Lipoic Acid Toxicities and Deficiencies

Alpha Lipoic Acid Deficiency

Because humans produce alpha lipoic acid endogenously, there is no documentation of a deficiency state. The amount required as an enzyme cofactor is supplied by the endogenous production. Supplementation of alpha lipoic acid is strictly for its antioxidant effect.

Alpha Lipoic Acid Toxicity

Supplementation with alpha lipoic acid is fairly safe, with little or no side effects. Occasionally, rash or diarrhea has developed with use. There have been no reports of an overdose with alpha lipoic acid.

As mentioned, alpha lipoic acid is also a metal chelator and long-term administration may promote deficiencies of trace minerals such as copper. Additional supplementation with trace minerals may prevent any such deficiency from developing.

In animal studies large doses have been lethal when administered with concurrent Vitamin B1 deficiency. This effect was prevented with treatment of Vitamin B1. Therefore, supplementation with Vitamin B1 or a B-complex compound is recommended to avoid any potential complications. [20]

References

1. http://www.pdrhealth.com/drug_info/nmdrugprofiles/herbaldrugs/101840.shtml Alpha Lipoic Acid. December 2004. 2. http://www.pdrhealth.com/drug_info/nmdrugprofiles/herbaldrugs/101840.shtml Alpha Lipoic Acid. December 2004.

3. http://www.pdrhealth.com/drug_info/nmdrugprofiles/herbaldrugs/101840.shtml Alpha Lipoic Acid. December 2004. 4. Henricksen EJ, Saengsirisuwan V. Exercise training and anti-oxidants: relief from oxidative stress and insulin resistance. Exerc Sport Sci Rev. 2003 Apr; 31(2): 79-84.

5. http://www.pdrhealth.com/drug_info/nmdrugprofiles/herbaldrugs/101840.shtml Alpha lipoic acid. December 2004.

6. Negrisanu G, Rosu M, Bolte B, Lefter D, Dabelea D. Effects of a 3-month treatment with antioxidant alpha lipoic acid in diabetic peripheral neuropathy. Rom J Inter Med. 1999 Jul-Sep; 37(3): 297-306.

7. Ruhnau KJ et al. Effect of a 3-week oral treatment with the antioxidant thioctic acid (alpha lipoic acid) in symptomatic diabetic polyneuropathy. Diabet Med. 1999 Dec; 16(12): 1040-1043.

8. Wollin SD, Jones PJ. Alpha lipoic acid and cardiovascular disease. J Nutr. 2003 Nov; 133(11): 3327-3330.

9. Kunt T et al. Alpha lipoic acid reduces expression of vascular cell adhesion molecule-1 and endothelial adhesion of human monocytes after stimulation with advanced glycation end products. Clin Sci (Lond). 1999 Jan; 96(1): 75-82.

10. Serbinova E, Khwanja S, Reznick AZ, Packer L. Thoictic acid protects against ischemia-reperfusion injury in the isolate perfused langendorff heart. Free Rad Res Commun. 1992; 17(1): 49-58.

11. Suziki YJ, Aggarwal BB, Packer L. Alpha lipoic acid is potent inhibitor of NF-kappa B activation in human T cells. Biochem Biophys Res Commun. 1992 Dec 30; 189(3): 1709-1715.

12. Pande V, Ramos MJ. Nuclear factor kappa B: a potential target for anti HIV chemotherapy. Curr Med Chem. 2003 Aug; 10(16): 1603-1615.

13. Ou P, Tritschler HJ, Wolff SP. Thioctic (lipoic) acid as a therapeutic metal chelating antioxidant? Biochem Pharmacol. 1995 Jun 29; 50(1): 123-126.

14. Sheline CT et al. Cofactors of mitochondrial enzymes attenuate copper induced neuronal cell death in vitro and vivo. Ann Neurol. 2002 Aug; 52(2): 195-204.

15. Patrick L. Mercury toxicity and antioxidants: Part I. Role of glutathione and alpha lipoic acid in the treatment of mercury toxicity. Altern Med Rev. 2002 Dec; 7(6): 456-471.

16. Bludovska M, Kotyzova D, Koutensky J, Eybl V. The influence of alpha lipoic acid on the toxicity of cadmium. Gen Phys Biophys. 1999 Oct 18; Spec No: 28-32.

17. Head KA. Natural therapies for ocular disorders Part II: Cataracts and glaucoma. Altern Med Rev. 2001 Apr; 6(2): 141-166.

18. Frolich L et al. ® but not (s) alpha lipoic acid stimulates deficient brain pyruvate dehydrogenase complex in vascular dementia but not in Alzheimer’s dementia. Neural Transm. 2004 Mar; 111(3): 295-310.

19. http://www.pdrhealth.com/drug_info/nmdrugprofiles/herbaldrugs/101840.shtml Alpha Lipoic Acid. December 2004.

20. Gaby A. Nutritional Therapy in Medical Practice. Nutrition Seminars, Seattle WA. 2001. Alpha Lipoic Acid: page 51.