Alpha lipoic acid is a powerful, natural antioxidant becoming recognized as having some unique properties in the therapy and prevention of a broad range of diseases. In addition to being a powerful antioxidant, this supplement helps the body use glucose, hence it's potential role in improving blood sugar control. ALA reduces complications from a high sugar diet. Lipoic acid is readily absorbed from the diet or as a supplement. This nutrient has a variety of benefits, particularly for diabetics.

The two types
If you're taking a conventional lipoic acid supplement, you're likely only getting half or less of the benefit of natural lipoic acid. The reason for this is that most alpha lipoic acid products on the market have both forms of lipoic acid: the synthetic S form, and the natural R form. R-lipoic acid is much more potent (2 times on average) than commonly sold synthetic lipoic acid which contains both the R and S forms. The S form is chemically the mirror image of the R form and cannot be used by the body, hence it is useless. Thus, 50 mg of R- alpha lipoic acid is equivalent to 100 mg of the synthetic version. 

R Alpha Lipoic Acid product 50 mg capsule, 90 Tablets - Physician Formulas

Highest quality. R-ALA is much more potent than commonly sold synthetic alpha lipoic acid which contains both the R and S forms. The S form is chemically the mirror image of the R form and is not useful to the body.

Supplement Facts
R Alpha Lipoic Acid capsule - 50 mg *

 

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Subscribe to a FREE Supplement Research Update newsletter. Twice a month you will receive an email with a review of several studies on various supplements and natural medicine topics, and their practical interpretation by Ray Sahelian, M.D. We plan to discuss alpha lipoic acid research in the newsletter as more information is published.

Suggested use: For long term use, 10 to 50 mg of R- alpha lipoic acid capsule a few times a week is quite adequate. For smaller amounts, you may open a capsule and put it in water or juice. The capsule is best taken in the morning with breakfast. If you plan to take higher amounts, please do so under medical supervision. Please realize that 50 mg of R Alpha Lipoic acid is as effective or more effective than 100 mg of conventional synthetic ALA.

* Alpha lipoic acid daily value not established. Be good to your body: Use Natural R Alpha Lipoic Acid rather than synthetic.

Dosage
As we found out about vitamin E, high doses of antioxidant supplements may not lead to more benefits. In fact, there comes a point where a supplement, no matter how benign, can become unhealthy if the doses are too high. For this reason I do not recommend more than 10 to 50 mg of alpha lipoic a day. There are products out there that have 300 mg of alpha lipoic per capsule. I am not convinced they are healthy to take, except perhaps to treat an existing medical condition for a specific period of time.    
   Animal research has shown that R ALA can more efficiently than other forms of lipoic acid increase or maintain levels of other antioxidants including COQ 10, vitamin C, vitamin E and glutathione, which often declines with age.

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Alpha lipoic acid benefit as an antioxidant
Lipoic acid can regenerate vitamin C from its oxidized form, dehydroascorbic acid. Lipoic acid can also potentially regenerate other antioxidants. Lipoic acid increases the levels of glutathione, a very important antioxidant normally found in our cells and responsible for mopping up all types of toxins and free radicals. Glutathione supplements, however, are not helpful since glutathione does not have the ability to cross cell membranes. Fortunately, both laboratory and animal studies have shown that alpha lipoic acid can stimulate the production of this antioxidant. This is particularly important during periods of excessive stress or exposure to radiation or toxic substances. Lipoic acid also acts as a powerful antioxidant in the brain and is likely to protect brain cells from toxins.

Conditions where alpha lipoic acid may benefit
Research in humans with lipoic acid is still incomplete. However, alpha lipoic may theoretically be worthwhile to explore in a variety of medical conditions, including diabetes, heart disease, hypertension, high cholesterol, Alzheimer's disease, Parkinson's disease, and Huntington's disease.

Alzheimer's disease
Alpha-lipoic acid as a new treatment option for Alzheimer's disease -- a 48 months follow-up analysis.
J Neural Transm Suppl. 2007. Department of Medical Rehabilitation and Geriatrics, Henriettenstiftung, Hannover, Germany.
In a previous study, 600mg alpha-lipoic acid was given daily to nine patients with Alzheimer's disease (receiving a standard treatment with choline-esterase inhibitors) in an open-label study over an observation period of 12 months. The treatment led to a stabilization of cognitive functions in the study group. Despite the fact that this study was not double-blinded, placebo-controlled and randomized, our data suggest that treatment with alpha-lipoic acid might be a successful 'neuroprotective' therapy option for Alzheimer's disease. However, a state-of-the-art phase II trial is needed urgently.

Alpha lipoic acid side effects
There are no indications that low doses of lipoic acid, such as 5 to 20 mg, have side effects. Higher doses could cause nausea or stomach upset, along with over-stimulation, fatigue, and insomnia. High doses could also potentially lower blood sugar. This is often beneficial to patients who have diabetes, but it requires close monitoring of blood sugar levels. We have had one report of 300 mg of alpha lipoic acid taken 3 times a day for three weeks led to atrial fibrillation. Another person emailed that a 50 mg dose of R lipoic acid made him feel his heart racing, he took it at the same time as his thyroid medication Levothyroid. Those with thyroid problems may consider taking half a capsule of a 50 mg R alpha lipoic acid dose.

Reports from users
Since Nov.2008 I've been taking alpha lipoic acid sustained release 400 mg twice a day and April 2009 the back of my head began itching and slowly got more intense to the point I had scratched till sores were on my head. As that slowly went away I started to itch on my lower back. Then that slowly moved from one place to another, my elbows then the stomach my upper back, knees the back of my legs. I itch all over now. Its not all the time.  I stopped taking it August 2009, now it is October 2009 and still itch sometimes. It is slowly getting better but you should see my body I have sores all over from scratching. always getting blood on my clothes. My doctor thinks I'm allergic to the sustained release in the product, do you think she's right, and how long does sustained release stay in your system? Do you think the dosage was just too high? I have used 15 tubes of hydrocortisone cream. She never suggested a break in taking it either, or taking a week off each month like you do.
    It's difficult to say whether the fillings in the product or ALA itself or the high dosage was the cause of the itching or there is something else that you are ingesting or being exposed to. Nevertheless, it is often a good idea to be cautious in the long term use of supplements.

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Memory
Feeding alpha lipoic acid and acetyl-l-carnitine to old rats improves performance on memory tasks by lowering oxidative damage and improving mitochondrial function.

Influence on thyroid gland
Do you know if there has been any problems with thyroid hormone levels with taking Alpha Lipoic Acid pills?

Effect of alpha-lipoic acid on the peripheral conversion of thyroxine to triiodothyronine and on serum lipid-, protein- and glucose levels.
Arzneimittelforschung. 1991 Dec; Institute of Clinical Biochemistry, University of Bonn, Fed. Rep. of Germany.
The influence of alpha-lipoic acid (LA, thioctic acid) on thyroid hormone metabolism and serum lipid-, protein- and glucose levels was investigated. In the first setup of experiments administration of LA together with thyroxine (T4) for 9 days suppressed the T4 induced increase of T3 generation by 56%. This suppression was similar to that affected by 6-propylthiouracil (54%). LA or T4 alone did not affect the cholesterol level, but together they led to a reduction. LA decreased the triglyceride level by 45%; the decrease induced by T4 or LA plus T4 was not significant. Total protein and albumin levels decreased by LA plus T4 treatment when compared to the LA control. The slight increase in glucose level by LA or T4 alone was not observed when they were administered together. In the second setup of experiments the administration of T4 for 22 days increased the serum T3 level 3-fold. When LA was combined with T4 and the treatment continued, the T3 production decreased by 22%. T4 reduced cholesterol level by 30%, and LA plus T4 further reduced it by 47%. The triglycerides were not affected. A moderate decrease in total protein was observed after treatment with T4 plus LA; T4 and LA plus T4 decreased the albumin level. The decrease in serum glucose by T4 recovers by LA treatment. These results demonstrate that alpha lipoic acid interferes with the production of T3 from T4 when it is co-administered with T4. The elevated level of T3, after T4 administration, is reduced by treatment with LA.   

Alpha lipoic acid and burning mouth syndrome
Burning mouth syndrome (BMS) has features of a neuropathy and could be related to the production of the toxic free radicals that are released in stress situations. Alpha-lipoic acid is an antioxidant able to increase the levels of intracellular glutathione and reduce free radicals. An older study shows benefit from ALA use while a newer study does not show any benefit over placebo. The problem with the newer study is that it was only 20 days long while the older study was for 2 months. Also, in the newer study, both placebo and ALA patients improved.

Alpha lipoic acid in burning mouth syndrome - a randomized double-blind placebo-controlled trial.
J Oral Pathol Med. 2009 Jan 23. Cavalcanti DR, da Silveira FR. Department of Oral Diagnosis, Dentistry School, University of Sao Paulo, Sao Paulo, Brazil.
The purpose of this study was to evaluate the effectiveness of alpha lipoic acid in the management of burning mouth syndrome symptoms through a randomized double-blind placebo-controlled trial. Patients were randomized into two cycles of treatment: one with alpha lipoic acid and one with placebo both administered in identical capsules. These cycles were separated by a washout period of 20 days. The level of reduction on burning was significant for both treatments. Considering the two cycles together, 22 patients reported at least some improvement after ALA use and 23 patients after placebo. Comparison of the oral assessment scores of the two cycles failed to demonstrate the effectiveness of ALA over placebo.

This study aimed to examine the effectiveness of alpha-lipoic acid in the therapy of burning mouth syndrome. This was a double blind, controlled study conducted for two months on 60 patients with constant burning mouth syndrom. Comparing alpha-lipoic acid (test) with cellulose starch (placebo). Following treatment with alpha lipoic acid, there was a symptomatic improvement, compared with placebo, with the majority showing at least some improvement after 2 months, thus supporting the hypothesis that burning mouth syndrome is a neuropathy. This improvement was maintained in over 70% of patients at the 1 year follow-up.

I am taking Alpha Lipoic Acid (400 mg. daily) for burning mouth syndrome. I believe it is helping me. However, I am reading so much on line that is conflicting. Can you tell me if this is a high dosage for me to be taking, and also does ALA cause hair loss?
    We are not in a position to comment on what your particular dosage should be since that is the role of your personal physician. Thus far we have not seen reports of ALA causing hair loss but not enough research is yet available regarding high dosage use for prolonged periods.

Loss of Smell (Olfactory)
Alpha lipoic acid may help regenerate loss of smell after a cold.

Loss of Taste
Researchers at the University of Medicine and Surgery, in Napoli, Italy, selected two homogenous groups, each of 22 patients with idiopathic dysgeusia, an altered perception of taste, matched for age and sex, for an open trial of alpha lipoic acid compared with placebo. The 22 patients in the study group were treated with alpha lipoic acid for 2 months. The 22 patients in the control group were treated for 2 months with carboxymethylcellulose. The latter group was then treated with alpha lipoic acid for 2 months. The results showed significant symptomatic improvements compared with placebo, in both groups of patients with dysgeusia treated with alpha lipoic acid, suggesting that idiopathic dysgeusia may be a neuropathy comparable to the burning mouth syndrome.

Alpha lipoic acid dosage
The ideal dose of alpha lipoic acid is not known at this time. As a daily maintenance, a dose of 10 to 50 mg a few times a week seems reasonable. Higher doses may be required to treat or prevent diabetic complications or other medical conditions. Some manufacturers sell alpha lipoic acid at 300 mg. I believe this is too high a dose to be taken for any length of time and may potentially cause problems.

Dietary supplementation with R alpha lipoic acid reverses the age-related accumulation of iron and depletion of antioxidants in the rat cerebral cortex.
Redox Rep. 2005;10(1):52-60. Suh JH, Moreau R, Heath SH, Hagen TM.
Department Biochemistry and Biophysics, Linus Pauling Institute, Oregon State University, Corvallis, Oregon
Accumulation of divalent metal ions (e.g. iron and copper) has been proposed to contribute to heightened oxidative stress evident in aging and neurodegenerative disorders. To understand the extent of iron accumulation and its effect on antioxidant status, we monitored iron content in the cerebral cortex of F344 rats by inductively coupled plasma atomic emission spectrometry (ICP-AES) and found that the cerebral iron levels in 24-28-month-old rats were increased by 80% relative to 3-month-old rats. Iron accumulation correlated with a decline in glutathione (GSH) and the GSH/GSSG ratio, indicating that iron accumulation altered antioxidant capacity and thiol redox state in aged animals. Because R) alpha Lipoic acid is a potent chelator of divalent metal ions in vitro and also regenerates other antioxidants, we monitored whether feeding R alpha lipoic acid (0.2% [w/w]; 2 weeks) could lower cortical iron and improve antioxidant status. Results show that cerebral iron levels in old R alpha lipoic acid fed animals were lower when compared to controls and were similar to levels seen in young rats. Antioxidant status and thiol redox state also improved markedly in old R alpha lipoic acid fed rats versus controls. These results thus show that R alpha lipoic acid supplementation may be a means to modulate the age-related accumulation of cortical iron content, thereby lowering oxidative stress associated with aging.

Alpha Lipoic acid in multiple sclerosis: a pilot study.
Mult Scler. 2005 Apr;11(2):159-65.
Yadav V, Marracci G, Lovera J, Woodward W, Bogardus K, Marquardt W, Shinto L, Morris C, Bourdette D. Department of Veterans Affairs Medical Center, Portland, OR
Alpha Lipoic acid is an antioxidant that suppresses and treats an animal model of multiple sclerosis, experimental autoimmune encephalomyelitis. The purpose of this study was to determine the pharmacokinetics (PK), tolerability and effects on matrix metalloproteinase-9 (MMP-9) and soluble intercellular adhesion molecule-1 (sICAMP-1) of oral Alpha Lipoic acid in patients with multiple sclerosis. Thirty-seven multiple sclerosis subjects were randomly assigned to one of four groups: placebo, ALA 600 mg twice a day, Alpha Lipoic acid 1200 mg once a day and ALA 1200 mg twice a day. Subjects took study capsules for 14 days. We found that subjects taking 1200 mg Alpha Lipoic acid had substantially higher peak serum Alpha Lipoic acid levels than those taking 600 mg and that peak levels varied considerably among subjects. We also found a significant negative correlation between peak serum ALA levels and mean changes in serum MMP-9 levels. There was a significant dose response relationship between Alpha Lipoic acid and mean change in serum sICAM-1 levels. We conclude that oral Alpha Lipoic acid is generally well tolerated and appears capable of reducing serum MMP-9 and sICAM-1 levels. Alpha Lipoic acid may prove useful in treating multiple sclerosis by inhibiting MMP-9 activity and interfering with T-cell migration into the CNS.

Alpha-Lipoic acid prevents diabetes mellitus in diabetes-prone obese rats.
Biochem Biophys Res Commun. 2005 Jan 7;326(1):197-202.
Several lines of evidence have suggested that triglyceride accumulation in skeletal muscle and pancreatic islets is causally related to type 2 diabetes mellitus. We recently showed that alpha lipoic acid, a potent antioxidant and cofactor of mitochondrial respiratory enzymes, reduces body weight of rodents by suppressing food intake and increasing energy expenditure. We sought to determine if alpha lipoic acid can prevent the development of diabetes mellitus in obese Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Most (78%) untreated OLETF rats showed glycosuria at 40 weeks of age, but this was completely prevented by alpha lipoic acid. Compared with untreated OLETF rats, alpha lipoic acid reduced body weight and protected pancreatic beta-cells from destruction. Alpha lipoic acid also reduced triglyceride accumulation in skeletal muscle and pancreatic islets. These results indicate that alpha lipoic acid prevents diabetes mellitus in obese diabetes-prone rats by reducing lipid accumulation in non-adipose tissue as well as in adipose tissue.

Plasma kinetics, metabolism, and urinary excretion of alpha lipoic acid following oral administration in healthy volunteers.
J Clin Pharmacol. 2003 Nov;43(11):1257-67.
R-alpha-lipoic acid is a natural occurring compound that acts as an essential cofactor for certain dehydrogenase complexes. The redox couple alpha lipoic acid /dihydrolipoic acid possesses potent antioxidant activity. Exogenous racemic alpha lipoic acid orally administered for the symptomatic treatment of diabetic polyneuropathy is readily and nearly completely absorbed, with a limited absolute bioavailability of about 30% caused by high hepatic extraction. Although the pharmacokinetics of the parent drug have been well characterized in humans, relatively little is known regarding the excretion of alpha lipoic acid and the pharmacokinetics of any metabolites in humans. In the present study, plasma concentration-time courses, urinary excreted amounts, and pharmacokinetic parameters of alpha lipoic acid metabolites were evaluated in 9 healthy volunteers after multiple once-daily oral administration of 600 mg racemic alpha lipoic acid. The primary metabolic pathways of alpha lipoic acid in man, S-methylation and beta-oxidation, were quantitatively confirmed by an HPLC-electrochemical assay. Despite the prolonged half-lives of the major metabolites compared to the parent drug, no evidence of accumulation was found. Mean values of 12% of the administered dose were recovered in the urine after 24 hours as the sum of alpha lipoic acid and its metabolites. The results of the present study revealed that urinary excretion of alpha lipoic acid and five of its main metabolites does not play a significant role in the elimination of alpha lipoic acid. Therefore, biliary excretion, further electrochemically inactive degradation products, and complete utilization of alpha lipoic acid as a primary substrate in the endogenous metabolism should be considered.

Randomized, placebo-controlled, double blind study on the clinical efficacy of a cream containing 5% alpha lipoic acid related to photoageing of facial skin.
Br J Dermatol. 2003 Oct;149(4):841-9.
Alpha lipoic acid or the reduced form dihydrolipoate (DHLA) is a potent scavenger with anti-inflammatory properties. Previous uncontrolled studies with topical treatment with 5% alpha-lipoic acid-containing creams indicate a beneficial effect on photoageing skin. The purpose of this study was to investigate whether a cream containing 5% alpha lipoic acid showed any advantages concerning a number of the criteria associated with ageing of the facial skin, compared with an identical cream lacking alpha-lipoic acid. Thirty-three women, mean age 54.4 years, were included in this controlled study. After randomization half the face was treated twice daily for 12 weeks with the alpha lipoic acid cream and the other half with the control cream. The following methods of assessment were used: self-evaluation by the test subjects, clinical evaluation, photographic evaluation and laser profilometry. Profilometry was performed before the start of treatment and at the end. All four methods of assessment showed a statistically significant improvement on the alpha lipoic acid -treated half of the face. Laser profilometry, the most objective method used, showed an average decrease in skin roughness of 50% on the alpha lipoic acid treated side, compared with 40% on the placebo-treated half of the face. It is indicated that 12 weeks of treatment with a cream containing 5% alpha lipoic acid improves clinical characteristics related to photoageing of facial skin.

Alpha Lipoic acid prevents hypertension, hyperglycemia, and the increase in heart mitochondrial superoxide production.
Midaoui AE. University of Montreal, Montreal, Canada. Am J Hypertens 2003 Mar;16(3):173-9.
The present study was designed to investigate whether the effects of dietary supplementation with alpha-lipoic acid could prevent the increase in mitochondrial superoxide production in the heart as well as the enhanced formation of advanced glycation end-products (AGE) that are associated with the development of hypertension and insulin resistance in chronically glucose-fed rats.Sprague Dawley rats were either given or not given a 10% D-glucose solution to drink during 4 weeks, combined either with a normal chow diet or with alpha-lipoic acid supplemented diet. The oxidative stress was evaluated by measuring the heart mitochondrial superoxide production using the lucigenin chemiluminescence method. The formation of AGE was also assessed in plasma and aorta.Chronic administration of glucose resulted in a 29% increase in blood pressure, 30% increase in glycemia, 286% increase in insulinemia, and 408% increase in insulin resistance index. Chronic glucose feeding also resulted in a 22% greater mitochondrial superoxide anion production in heart and in an increase of 63% in AGE content in aorta. Increases in blood pressure, aorta AGE content and heart mitochondrial superoxide production were prevented in the rats fed glucose supplemented with lipoic acid. The simultaneous treatment with lipoic acid also attenuated the rise in insulin levels as well as in insulin resistance in the glucose fed rats.These findings demonstrate that alpha-lipoic acid supplementation prevents development of hypertension and hyperglycemia, presumably through its antioxidative properties, as reflected by prevention of an increase in heart mitochondrial superoxide anion production and in AGE formation in the aorta of chronically glucose treated rats.

Effects of alpha lipoic acid on microcirculation in patients with peripheral diabetic neuropathy.
Haak E,. University Hospital, Frankfurt, Germany.
Diabetic polyneuropathy is a serious complication in patients with diabetes mellitus. In addition to the maintenance of a sufficient metabolic control, alpha-lipoic acid (Thioctacid, Asta Medica) is known to have beneficial effects on diabetic polyneuropathy although the exact mechanism by which alpha-lipoic acid exerts its effect is unknown. In order to study the effect of alpha-lipoic acid on microcirculation in patients with diabetes mellitus and peripheral neuropathy one group of patients received 1200 mg alpha-lipoic acid orally per day over 6 weeks (trial 1). A second group of patients was studied before and after they had received 600 mg alpha lipoic acid or placebo intravenously over 15 minutes in order to investigate whether ALA has an acute effect on microcirculation (trial 2). The results demonstrate that in patients with diabetic polyneuropathy alpha-lipoic acid improves microcirculation as indicated by an increased perfusion reserve on demand. The observed effects are apparently acute effects. With the restriction of the pilot character of this investigation the findings support the assumption that alpha-lipoic acid might exert its beneficial effects at least partially by improving microcirculation which is likely to occur also at the level of the vasa nervorum.

Idiopathic dysgeusia; an open trial of alpha lipoic acid (ALA) therapy. Int J Oral Maxillofac Surg 2002 Dec;31(6):625-8. Stomatology Clinic II, 
Femiano F, Scully C, Gombos F.

Alpha Lipoic acid in the treatment of smell dysfunction following viral infection of the upper respiratory tract. Hummel T. Laryngoscope 2002 Nov;112(11):2076-80. Department of Otorhinolaryngology, University of Dresden Medical School, Germany.

Burning mouth syndrome (BMS): double blind controlled study of alpha-lipoic acid (thioctic acid) therapy. Femiano F, Scully C.
J Oral Pathol Med 2002 May;31(5):267-9. Stomatology Clinic II, University of Medicine and Surgery, Napoli, Italy.

Alpha Lipoic Acid Animal Studies
(R)-alpha-lipoic acid reverses the age-associated increase in susceptibility of hepatocytes to tert-butylhydroperoxide both in vitro and in vivo.
Antioxid Redox Signal. 2000 Fall;2(3):473-83.
Hepatocytes were isolated from young (3-5 months) and old (24-28 months) rats and incubated with various concentrations of tert-butylhydroperoxide (t-BuOOH). The t-BuOOH concentration that killed 50% of cells (LC50) in 2 hr declined nearly two-fold from 721 +/- 32 microM in cells from young rats to 391 +/- 31 microM in cells from old rats. This increased sensitivity of hepatocytes from old rats may be due, in part, to changes in glutathione (GSH) levels, because total cellular and mitochondrial GSH were 37.7% and 58.3% lower, respectively, compared to cells from young rats. Cells from old animals were incubated with either (R)- or (S)-lipoic acid (100 microM) for 30 min prior to the addition of 300 microM t-BuOOH. The physiologically relevant (R)-form, a coenzyme in mitochondria, as opposed to the (S)-form significantly protected hepatocytes against t-BuOOH toxicity. Dietary supplementation of (R)-lipoic acid [0.5% (wt/wt)] for 2 weeks also completely reversed the age-related decline in hepatocellular GSH levels and the increased vulnerability to t-BuOOH as well. An identical supplemental diet fed to young rats did not enhance the resistance to t-BuOOH, indicating that antioxidant protection was already optimal in young rats. Thus, this study shows that cells from old animals are more susceptible to oxidant insult and (R)-lipoic acid, after reduction to an antioxidant in the mitochondria, effectively reverses this age-related increase in oxidant vulnerability.

Alpha-Lipoic acid, an anti-obesity agent?
Expert Opin Investig Drugs. 2004 Dec;13(12):1641-3.
Obesity shortens life expectancy and is a risk factor for hypertension and Type 2 diabetes. When added to the standard chow of Sprague-Dawley or Otsuka Long-Evans Tokushima Fatty rats, alpha-lipoic acid (0.5% weight/weight) reduced body weight and food intake. alpha-Lipoic acid also increased whole-body energy expenditure. It exerts its effects by suppressing hypothalamic AMP-activated protein kinase. Long-term studies to determine whether these anti-obesity effects are maintained in animals are required before alpha-lipoic acid is considered for clinical trial in human obesity.

Effects of alpha-lipoic acid supplementation on maternal diabetes-induced growth retardation and congenital anomalies in rat fetuses.
Mol Cell Biochem. 2004 Jun;261(1-2):123-35.
The mechanism of diabetic embryopathy is not known. Excessive reactive oxygen species (ROS) produced in diabetes may be causally related to fetal anomalies. The objective of this study was to determine whether supplementation with the antioxidant alpha lipoic acid could prevent maternal diabetes-related fetal malformations and intrauterine growth retardation (IUGR) in rats. Pregnant rats were non-treated (Group I) or made diabetic on gestation day (GD) 2 by injecting streptozotocin (Group II). Group III was injected with 20 mg kg(-1) of alpha lipoic acid daily starting on GD 6 and continued through GD 19. Group IV was administered only Tris buffer on the corresponding days. Group V was a set of STZ-treated animals, which were supplemented with a daily dose of 20 mg kg(-1) of alpha lipoic acid from GD 6 through GD 19. All fetuses were collected on GD 20. Alpha Lipoic acid did not affect the blood sugar levels of diabetic animals significantly but improved their body weight gain and reduced food and water consumption. Diabetic group had a high incidence of embryonic resorption, IUGR, craniofacial malformations, supernumerary ribs and skeletal hypoplasia. Alpha Lipoic acid significantly reduced these abnormalities. These data support the hypothesis that ROS are causally related to fetal maldevelopment and IUGR associated with maternal diabetes in the rat. They also highlight the possible role of antioxidants in the normal processes of embryo survival, growth and development.

Alpha-Lipoic acid inhibits airway inflammation and hyperresponsiveness in a mouse model of asthma.
J Allergy Clin Immunol. 2004 Aug;114(2):429-35.
Oxidative stress may play an important role in the pathogenesis of bronchial asthma. OBJECTIVE: We evaluated the therapeutic effect of alpha-lipoic acid, a nonenzymatic antioxidant, in a mouse model of asthma. RESULTS: Compared with untreated asthmatic mice, mice treated with alpha-lipoic acid had significantly reduced airway hyperresponsiveness, a lower proportion of eosinophils among BAL cells, and significantly improved pathologic lesion scores of the lungs. alpha-Lipoic acid also significantly reduced serum OVA-specific IgE concentrations, IL-4 and IL-5 concentrations in BAL fluid, and intracellular reactive oxygen species and nuclear factor kappaB DNA-binding activity. CONCLUSION: These results suggest that oxidative stress plays an important role in asthmatic airway inflammation and that alpha-lipoic acid may be useful as adjuvant therapy for bronchial asthma.

Alpha-lipoic acid increases Na+K+ATPase activity and reduces lipofuscin accumulation in discrete brain regions of aged rats.
Ann N Y Acad Sci. 2004 Jun;1019:350-4.
A convincing link between oxidative stress and neurodegenerative diseases has been found with the knowledge that it actually damages neuronal cells in culture. We analyzed the effect of DL-alpha-lipoic acid on lipofuscin and Na(+)K(+) ATPase in discrete brain regions of young and aged rats. In aged rats, the level of lipofuscin was increased, and the activity of Na(+)K(+)ATPase was decreased. Intraperitoneal administration of lipoic acid to aged rats led to a duration-dependent reduction and elevation in lipofuscin and enzyme activity, respectively, in the cortex, cerebellum, striatum, hippocampus, and hypothalamus of the brain. These results suggest that lipoic acid, a natural metabolic antioxidant, should be useful as a therapeutic tool in preventing neuronal dysfunction in aged individuals.

Alpha Lipoic acid as a potential therapy for chronic diseases associated with oxidative stress.
Smith AR, et al. Dept. of Biochemistry and the Linus Pauling Institute, Oregon State University, Corvallis, Oregon
Curr Med Chem. 2004 May;11(9):1135-46.
alpha-Lipoic acid, a naturally occurring dithiol compound, has long been known as an essential cofactor for mitochondrial bioenergetic enzymes. Aside from its enzymatic role, in vitro and in vivo studies suggest that alpha-Lipoic acid also acts as a powerful micronutrient with diverse pharmacologic and antioxidant properties. Pharmacologically, alpha-Lipoic acid improves glycemic control, polyneuropathies associated with diabetes mellitus, and effectively mitigates toxicities associated with heavy metal poisoning. As an antioxidant, alpha Lipoic acid directly terminates free radicals, chelates transition metal ions (e.g. iron and copper), increases cytosolic glutathione and vitamin C levels and prevents toxicities associated with their loss. These diverse actions suggest that alpha-Lipoic acid acts by multiple mechanisms both physiologically and pharmacologically, many of which are only now being explored. Herein, we review the known biochemical properties of alpha-Lipoic acid with particular reference to how alpha-Lipoic acid may be an effective agent to ameliorate certain pathophysiologies of many chronic diseases.

Alpha Lipoic acid restores antioxidant system in tissues of hyperinsulinaemic rats.
Thirunavukkarasu V. Annamalai University, Annamalai Nagar, Tamil Nadu, India. Indian J Med Res. 2003 Sep;118:134-40.
Feeding rats with high fructose induces insulin resistance, hyperinsulinaemia, elevation of blood glucose level and impaired glucose tolerance. Oxidative stress plays a vital role in pathology associated with insulin resistance. The present study was to investigate the effects of alpha-lipoic acid on the oxidant-antioxidant balance in liver and kidney of high fructose-fed rats. Male Wistar rats (170-180 g) were divided into six groups. The control group received diet containing starch; the fructose group was given a high fructose diet (>60% of total calories); the third and fourth groups were given fructose diet and administered with two different doses of alpha lipoic acid as low dose (35 mg/kg body weight) and high dose (70 mg/kg bw) intraperitoneally using olive oil as vehicle; the fifth group received control diet and was administered with alpha lipoic acid (70 mg/kg bw); the sixth group received the control diet and olive oil. The rats were maintained in their respective dietary regimen for 20 days. Lipid peroxidation indices and antioxidant status in liver and kidney were quantitated. RESULTS: The rats fed fructose showed increased levels of lipid hydroperoxides, thiobarbituric acid reactive substances (TBARS), conjugated dienes, and impaired antioxidant defence potential as evidenced by a decrease in the levels of non-enzymatic and enzymatic antioxidants. Treatment with alpha-lipoic acid to the fructose-fed rats mitigated these alterations and alpha-lipoic acid was effective uniformly at both the closes. Increased lipid peroxidation and inadequate antioxidant system are observed in the high dose fructose-fed rats. ALA administration restored the antioxidant potential and lowered lipid peroxidation. These findings strengthen the utility of alpha-lipoic acid in the management of insulin resistance and associated pathology.

R-alpha-lipoic acid-supplemented old rats have improved mitochondrial function, decreased oxidative damage, and increased metabolic rate.
FASEB J. 1999 Feb;13(2):411-8.
A diet supplemented with R lipoic acid, a mitochondrial coenzyme, was fed to old rats to determine its efficacy in reversing the decline in metabolism seen with age. Young (3 to 5 months) and old (24 to 26 months) rats were fed an AIN-93M diet with or without (R)-lipoic acid (0.5% w/w) for 2 wk, killed, and their liver parenchymal cells were isolated. Hepatocytes from untreated old rats vs. young controls had significantly lower oxygen consumption (P<0. 03) and mitochondrial membrane potential. (R)-Alpha Lipoic acid supplementation reversed the age-related decline in O2 consumption and increased mitochondrial membrane potential. Ambulatory activity, a measure of general metabolic activity, was almost threefold lower in untreated old rats vs. controls, but this decline was reversed (P<0.005) in old rats fed (R)-lipoic acid. Both glutathione and ascorbic acid levels declined in hepatocytes with age, but their loss was completely reversed with (R)-lipoic acid supplementation. Thus, R-lipoic acid supplementation improves indices of metabolic activity as well as lowers oxidative stress and damage evident in aging.

Alpha Lipoic acid laboratory studies
(R)-alpha-lipoic acid reverses the age-related loss in GSH redox status in post-mitotic tissues: evidence for increased cysteine requirement for GSH synthesis.
Arch Biochem Biophys. 2004 Mar 1;423(1):126-35.
Age-related depletion of GSH levels and perturbations in its redox state may be especially deleterious to metabolically active tissues, such as the heart and brain. We examined the extent and the mechanisms underlying the potential age-related changes in cerebral and myocardial GSH status in young and old F344 rats and whether administration of (R)-alpha-lipoic acid (LA) can reverse these changes. These results demonstrate that LA is an effective agent to restore both the age-associated decline in thiol redox ratio as well as increase cerebral GSH levels that otherwise decline with age.

Alpha Lipoic acid review abstract
Lipoic acid as a potential first agent for protection from mycotoxins and treatment of mycotoxicosis.
Arch Environ Health. 2003 Aug;58(8):528-32.
Mycotoxins -- toxic substances produced by fungi or molds -- are ubiquitous in the environment and are capable of damaging multiple biochemical mechanisms, resulting in a variety of human symptoms referred to collectively as "mycotoxicosis." In fact, mycotoxins mimic multiple xenobiotics, not only with respect to their ultimate damage, but also in their routes of detoxification. This suggests potential therapeutic options for the challenging treatment of mycotoxicosis. In this brief review, the author examines the use of alpha lipoic acid as an example of an inexpensive and available nutrient that has been shown to protect against, or reverse, the adverse health effects of mycotoxins.

Alpha Lipoic cream and Skin
Alpha Lipoic acid 5% skin cream can reduce damage from sun exposure.

A brief history
In the fall of 1950, a team of scientists headed by Dr. Lester Reed, from the Department of Chemistry at the University of Texas in Austin, isolated a compound that affected the metabolism of glucose. They named this compound alpha-lipoic acid. The term lipoic refers to "lipid" or fat, since Alpha lipoic acid was not soluble in water. Since 1950, hundreds of articles have been published on Alpha lipoic acid. Initially, scientists focused on the role of Alpha lipoic acid in sugar metabolism. However, in the Alpha lipoic acidte 1980s, Alpha lipoic acid’s powerful antioxidant capabilities were discovered. The research with this nutrient has accelerated over the past few years. Various patents have been taken, and researchers are testing Alpha lipoic acid for its potential in fighting infections and inflammation, protecting nerve cells, treating cardiovascular diseases, tumors, allergies, shielding against stomach ulcers, and so on. Naturally, there’s no guarantee that Alpha lipoic acid will turn out to be appropriate for all these conditions.
 
The ideal antioxidant?
Our foods, especially fruits and vegetables, contain countless antioxidants. They are all important, and taking Alpha lipoic acid is certainly not a substitute for eating a diet loaded with refined sugars, desserts, and high-fat junk.
However, Alpha lipoic acid offers some benefits you won’t find in other antioxidants. In a 1995 review article published in the journal Free Radical Biology and Medicine, one of the leading scientists in the area of antioxidant chemistry, Lester Packer, Ph.D., from the University of California at Berkeley, reports on the uniqueness of Alpha lipoic acid. He even comes close to calling Alpha lipoic acid the "ideal" antioxidant, for the following reasons:
Alpha lipoic acid is readily absorbed from the diet or as a supplement.
It can regenerate vitamin C from dehydroascorbic acid, its oxidized form.
It can potentially regenerate other antioxidants.
It increases the levels of glutathione, a very important antioxidant normally found in our cells.
It can be used therapeutically in a variety of medical diseases.
Alpha lipoic acid can enhance the synthesis of glutathione, the main antioxidant within our cells. Glutathione effectively mops up all types of toxins and free radicals. However, we cannot take supplements of this antioxidant since it is unable to cross cell membranes. Fortunately, both laboratory and animal studies have shown that Alpha lipoic acid can stimulate the production of glutathione. This is particularly important during periods of excessive stress or exposure to toxic substances, or even exposure to radiation.
It seems that Alpha lipoic acid can even pitch in and help when the body is lacking vitamin E. When laboratory animals were depleted of their vitamin E stores because their diet lacked this nutrient, they displayed obvious symptoms of vitamin E deficiency. However, when their diet was supplemented with Alpha lipoic acid, the animals were completely protected.

What about side effects?
Low doses of Alpha lipoic acid, such as 10 to 50 mg, do not cause side effects of any significance. However, higher doses could cause gastrointestinal symptoms of nausea or stomach upset. Extremely high doses could potentially lead to very low blood sugar. For long-term use, we do not recommend that you take more than 100 mg a day until extensive human studies are completed. People don’t always realize that even a good thing can turn bad. Some antioxidants are thought to turn into pro-oxidants (oxidation-causing) in excessive dosages. Also, the body needs some oxidation-type chemicals in order to fight off certain germs. It may be unwise to mop up all oxidants in the body, since some may play certain key roles. It would certainly be wise to make your healthcare practitioner aware of the supplements you are taking.

Alpha Lipoic acid and aging
Glucose (sugar) has been implicated in the aging process because of its ability to react with some proteins, such as collagen, to produce glycation. That is, the glucose molecule attaches to some amino acids of a protein and makes the protein less functional, leading to malfunction. The initial phase of this attachment is called glycation.
As we age, the amount of glycation of the proteins in our bodies tends to increase. We should also note that blood sugar generally increases as we age. The glycation of the collagen in our tendons and arteries increases with age, in proportion to the increase in blood glucose that occurs with aging.
However, restricting calories can help prevent this age-related increase in glycation. In other words, avoiding excess sugar and excess calorie consumption could theoretically, over the years and decades, help our proteins stay healthier. Practical ways to use this information include:
Eat small, frequent meals throughout the day instead of one or two excessively large ones. Eating these small meals, or snacks, will help maintain your blood sugar at a relatively steady state, instead of wide fluctuations.
Make sure to get some protein with each meal. Avoid a purely carbohydrate meal, except when you want to induce sleep at night. Carbohydrates, eaten an hour or two before bed, will help you feel sleepy.
Even relatively "healthy" drinks, such as fruit juices, can increase blood sugar significantly when consumed in large amounts, such as six ounces or more. Many people quickly gulp down eight ounces of orange juice in the morning, in addition to a cup of coffee laced with a teaspoon or two of sugar.
Alpha lipoic acid could also help lower the rate of glycation. According to a study published in 1997, Alpha lipoic acid was found to reduce glycation of proteins in human tissues. This is an important finding not only for diabetics, but for all of us.

For prevention and anti-aging
Because of its effectiveness as an antioxidant, it would seem logical for anyone who takes supplemental antioxidants to consider adding Alpha lipoic acid to his or her regimen. The ideal dose of Alpha lipoic acid as an antioxidant has not been determined. However, 50 mg a day, or every other day, would certainly be reasonable. (Note: Taking more for bodybuilding purposes has been show to be okay.) You may also need Alpha lipoic acid in times of stress, infection, or other types of illness. As with many nutrients and medicines, our philosophy is to take occasional breaks and not use them for a few days.

How will Alpha lipoic acid make you feel?
We, the authors, have noted that the ingestion of Alpha lipoic acid can often lead to a mild, real feeling of well-being. Interestingly, there’s also a slight visual enhancement that occurs. However, this visual enhancement is not as dramatic as that of Eyesight Rx.

Final note
Alpha lpoic acid is an exciting addition to the list of nutrients, herbs, and hormones that can treat disease in a safer and more natural way, and help you become healthier. This nutrieint offers many benefits, but, as with any medicine, we should not think of it as a magic bullet that can cure all types of diseases. The human body is complicated, with countless chemical reactions going on at any one time. Alpha lipoic acid, when used appropriately, can – either by itself or in combination with proper exercise and diet – offer additional therapeutic benefits.
   Over the next few years, we are likely to see the research in this field accelerate. In the meantime, we hope that Alpha lipoic acid can help you with your particular medical condition.

Alpha Lipoic Acid supplement emails
Q. Hello Dr. Sahelian, I love your  newsletter. Could you please talk about the difference between alpha lipoic acid and the R+ alpha lipoic acid. I have done extensive research and can't understand why the R+ is not being used. Are you using the R+ in your products?? The regular alpha lopic is 50% synthetic, and 50% pure alpha lopic. The R+ is 100% pure alpha lipoic acid, and can enter the mitochondria 100%. Using the other, only the 50% which is pure can enter the mitochondria.
   A. We have a new product by Physician Formulas which is R- Alpha Lipoic Acid and pure so that we do not waste half of a capsule on synthetic lipoic acid.

Q. What do you recommend as a daily intake of supplemental lipoic acid?
   A. Nobody really knows what the ideal daily intake of apha lipoic acid should be. I would guess based on my knowledge that a dose of 10 to 20 mg a day of lipoic acid would be a cautious was to supplement. Or, a 50 mg tablet could be taken a couple of times a week.

Q. I recently read of a study perfromed in Germany using Alpha Lipoic Acid in the treatment of patients with Alzheimers Disease. In the study it was found that the study group took 600mg of ALA daily and their symptoms were halted without further deteriation. The dosage included 50mc of Biotin per 100 mg of alpha lipoic acid. In reading Dr. Sahelian's comments on the website regarding alpha lipoic acid, I am curious if he has heard of the study since his feeling on high dosages of alpha lipoic acid is not recommended.
   A. Usually when studies are done, a high amount of a substance, such as alpha lipoic acid, is used since the researchers want to measure a difference. However this does not mean that this is the right dosage to take forever, since 600 mg alpha lipoic acid may be good for a short while but could create other problems if used for months or years. There is also a difference in dosage of a supplement depending on whether it is used therapeutically or just a health promoting maintenance dosage.

Q. I have been taking alpha lipoic acid R now for over a month and I see no effect from it at all. I am 59, work out twice a week with strength training and I also coach and play field hockey once a week. I was hoping that the r alpha lipoic capsules would help reduce the fat accumulation around my waist but they appear to have had no effect. I would really like to remove the fat from around my waist since it can cause all kinds of complications as one gets older.
   A. R alpha lipoic acid is not a supplement indicated for weight loss. To lose weight, walking an hour a day is the best option, along with eating less, particularly at night.

Q. I read that you recommend no more than 10-50mg/day of alpha-lipoic acid supplement. At the advice of a consultant at a GNC store, I started taking 900 mg (3-300mg tabs/day) of alpha-lipoic acid supplement on May 2nd. On May 18th I suffered atrial fibrillation/flutter which required hospitalization to get my heart in normal sinus rhythm. I've got a trans-esophageal echogram and an ablation scheduled. I am post-menopausal, healthy, non-smoking, active, normal weight. I had open heart/bypass surgery in 2001 for a blocked LADA, but was discharged from cardiac follow-up. Apparently this has no bearing on the current incident. This is just for your information, in that I believe the high doses of alpha-lipoic acid had everything to do with this incident.
   A. Please keep us updated.

Q. I was wondering why you have formulated acetyl l-carnitine in 300 mg capsules and alpha lipoic acid in only 50 mg capsules. I've heard that acetyl l-carnitine needs to be taken with alpha lipoic acid supplement and had imagined they would need to be taken at a ratio of 1:1, so that your body has enough anti-oxidant to match with the acetyl l-carnitine?
   A. People have a misconception that the more antioxidants they take, the better, but this is not true, side effects can occur on high doses.

Q. I noticed a Doctor's Best ad promoting a "stabilized" R-lipoic acid as much better absorbed -- any thoughts?
   A. We don't know what them mean by this. R lipoic acid is quite potent and effective as is, we don't see the need to make any changes. In fact, many people may be overdosing themselves using too high dosages of alpha lipoic acid, and hence better absorption, even if true (which we seriously doubt), does not seem such a good idea.

Q. Does alpha lipoic acid cause weight loss?
   A. We have not seen such research but is is possible that high alpha lipoic dosage can cause decrease in appetite, whether taking alpha lipoic acid supplement leads to long term weight loss is not known. High dosages can lead to side effects.

Q. I am looking at taking Lipoic CR which has 800mg of alpha-lipoic acid and 200 mcg biotin in one tablet. I have diabetes and this product helps.
   A. There may be heart rhythm problems taking 800 mg of alpha lipoic acid.

I had been taking 800 mg. of ALA for months to lower my blood sugar under the care of a practitioner. I stopped a few weeks ago when I read in your website that this high dosage could cause atrial fibrillation and arrhythmia. Consequently, my sugar has shot up even though I'm very conscientious about what I eat. I also have open angle glaucoma. I'm 56 years old. I'd like to understand the connection between alpha lipoic acid and atrial fibrillation and arrhythmia. How could ala bring these about?
    I am not sure how this occurs, and it does not happen in everyone. Some people are able to tolerate high dosages without heart rhythm disturbances whereas others are very susceptible.