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Jan, 2004

LIPOIC ACID

LIPOIC ACID:  Lipoic acid may positively affect the hippocampus, associated with memory.  In mice, it reduces weight, improves muscle mass, and lowers triglycerides.  They are doing a clinical trial where people take 600 mg a day, in the morning on an empty stomach.  So people could experience dizziness initially. (Link: Lipoic acid: Source: Linus Pauling Institute Research Newsletter Spring/Summer 2009; added 6/2009)

 Alpha-Lipoic acid, known as ALA, is a critical catalytic part of the key enzymes which produce energy in the body, both pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase. Without ALA, energy producing metabolism would shut down. Even a shortage would leave one feeling tired. To compensate for the inability to burn fat effectively, fat molecules will be stored, producing obesity. Taken together with N-Acetyl-carnitine, this nutrient can turn old rats into young ones. See the essay on carnitine which explains this.

"Cigarette smoking is a risk factor for atherosclerosis. It is conceivable that reactive chemical components in cigarette smoke may adversely affect reverse cholesterol transport at the level of lecithin: cholesterol acyltransferase (LCAT) and promote atherogenesis. .. Addition of glutathione, but not ascorbate, to plasma prevented loss of LCAT activity caused by cigarette smoke." Chen C; Loo G, "Inhibition of lecithin: cholesterol acyltransferase activity in human blood plasma by cigarette smoke extract and reactive aldehydes", J Biochem Toxicol 1995 Jun;10(3):121-8

Ziegler D; Schatz H; Conrad F; Gries FA; Ulrich H; Reichel G, "Effects of treatment with the antioxidant alpha-lipoic acid on cardiac autonomic neuropathy in NIDDM patients. A 4-month randomized controlled multicenter trial (DEKAN Study). Deutsche Kardiale Autonome Neuropathie", Diabetes Care 1997 Mar;20(3):369-73

"To evaluate the efficacy and safety of oral treatment with the antioxidant alpha-lipoic acid (ALA) in NIDDM patients with cardiac autonomic neuropathy (CAN), assessed by heart rate variability. (HRV). ..In a randomized, double-blind placebo-controlled multicenter trial (Deutsche Kardiale Autonome Neuropathie [DEKAN] Study), NIDDM patients with reduced HRV were randomly assigned to treatment with daily oral dose of 800 mg ALA (n = 39) or placebo (n = 34) for 4 months... Seventeen patients dropped out of the study (ALA n = 10; placebo n = 7). Mean blood pressure and HbA1 levels did not differ between the groups at baseline and during the study, but heart rate at baseline was higher in the group treated with ALA (P < 0.05). .. These findings suggest that treatment with ALA using a well-tolerated oral dose of 800 mg/day for 4 months may slightly improve CAN in NIDDM patients.

Schleicher ED; Wagner E; Nerlich AG, "Increased accumulation of the glycoxidation product N(epsilon)-(carboxymethyl)lysine in human tissues in diabetes and aging", J Clin Invest 1997 Feb 1;99(3):457-68

ABSTRACT: N(epsilon)-(Carboxymethyl)lysine (CML), a major product of oxidative modification of glycated proteins, has been suggested to represent a general marker of oxidative stress and long-term damage to proteins in aging, atherosclerosis, and diabetes. To investigate the occurrence and distribution of CML in humans an antiserum specifically recognizing protein-bound CML was generated. The oxidative formation of CML from glycated proteins was reduced by lipoic acid, aminoguanidine, superoxide dismutase, catalase, and particularly vitamin E and desferrioxamine. Immunolocalization of CML in skin, lung, heart, kidney, intestine, intervertebral discs, and particularly in arteries provided evidence for an age-dependent increase in CML accumulation in distinct locations, and acceleration of this process in diabetes. "

Jacob S; Henriksen EJ; Tritschler HJ; Augustin HJ; Dietze GJ, "Improvement of insulin-stimulated glucose-disposal in type 2 diabetes after repeated parenteral administration of thioctic acid" [note thioctic acid is lipoic acid], Exp Clin Endocrinol Diabetes 1996;104(3):284-8

"Insulin resistance of skeletal muscle glucose uptake is a prominent feature of Type II diabetes (NIDDM); therefore, pharmacological intervention should aim to improve insulin sensitivity. Thioctic acid (TA, which is the same as lipoic acid), a naturally occurring compound, was shown to enhance glucose utilization in various experimental models after acute and chronic administration. It also increased insulin-stimulated glucose disposal in patients with NIDDM after acute administration. ... This is the first clinical study to show that a ten day administration of TA is able to improve resistance of insulin-stimulated glucose disposal in NIDDM. Experimental data suggest several mechanisms in the mode of action. As the present investigation was an uncontrolled pilot trial, the encouraging results call for controlled studies to further elucidate the clinical relevance of the findings and the mode of action of this compound."

Ziegler D; Hanefeld M; Ruhnau KJ; Meissner HP; Lobisch M; Schutte K; Gries FA, "Treatment of symptomatic diabetic peripheral neuropathy with the anti-oxidant alpha-lipoic acid. A 3-week multicentre randomized controlled trial (ALADIN Study)", Diabetologia 1995 Dec;38(12):1425-33

"Anti-oxidant treatment has been shown to prevent nerve dysfunction in experimental diabetes mellitus, thus providing a rationale of potential therapeutic value for diabetic patients. The effects of the anti-oxidant alpha-lipoic acid (thioctic acid) were studied in a 3-week multicentre, randomized, double-blind placebo-controlled trial (Alpha-Lipoic Acid in Diabetic Neuropathy; ALADIN) in 328 non-insulin-dependent diabetic patients with symptomatic peripheral neuropathy who were randomly assigned to treatment with intravenous infusion of alpha-lipoic acid using three doses (1200, 600, or 100 mg ALA) or placebo (PLAC). Neuropathic symptoms (pain, burning, paraesthesiae, and numbness) were scored at baseline and at each visit (days 2-5, 8-12, and 15-19) prior to infusion. .. The response rates after 19 days, defined as an improvement in the total symptom score of at least 30%, were 70.8% in ALA 1200, 82.5% in ALA 600, 65.2% in ALA 100, and 57.6% in PLAC (ALA 600 vs PLAC; p = 0.002). The total scale of the Pain Adjective List was significantly reduced in ALA 1200 and ALA 600 as compared with PLAC after 19 days (both p < 0.01). The rates of adverse events were 32.6% in ALA 1200, 18.2% in ALA 600, 13.6% in ALA 100, and 20.7% in PLAC. These findings substantiate that intravenous treatment with alpha-lipoic acid using a dose of 600 mg/day over 3 weeks is superior to placebo in reducing symptoms of diabetic peripheral neuropathy, without causing significant adverse reactions."

TITLE: [Lipoic acid as a means of metabolic therapy of open-angle glaucoma]

AUTHOR: Filina AA; Davydova NG; Endrikhovskii SN; Shamshinova AM

SOURCE: Vestn Oftalmol 1995 Oct-Dec;111(4):6-8

"A total of 45 patients (90 eyes) with stages I and II open-angle glaucoma (OAG) were examined, 26 of these were administered lipoic acid in a daily dose of 0.075 g for 2 months and 19 were given 0.15 g daily for 1 month. Control group consisted of 31 patients with OAG... Improvement was attained in approximately 45-47.5% of examined eyes, and was more often seen in patients with stage II OAG: in 57-58% eyes. The effect of lipoic acid may be explained by its antioxidant properties and direct influence on ocular tissue metabolism."

Barbiroli B; Medori R; Tritschler HJ; Klopstock T; Seibel P; Reichmann H; Iotti S; Lodi R; Zaniol P, "Lipoic (thioctic) acid increases brain energy availability and skeletal muscle performance as shown by in vivo 31P-MRS in a patient with mitochondrial cytopathy",, J Neurol 1995 Jul;242(7):472-7

"A woman affected by chronic progressive external ophthalmoplegia and muscle mitochondrial DNA deletion was studied by phosphorus magnetic resonance spectroscopy (31P-MRS) prior to and after 1 and 7 months of treatment with oral lipoic acid. Before treatment a decreased phosphocreatine (PCr) content was found... All of these findings indicated a deficit of mitochondrial function in both brain and muscle. Treatment with 600 mg lipoic acid daily for 1 month resulted in a 55% increase of brain [PCr], 72% increase of phosphorylation potential, and a decrease of calculated [ADP] and rate of energy metabolism. After 7 months of treatment MRS data and mitochondrial function had improved further. Treatment with lipoate also led to a 64% increase in the initial slope of the work-energy cost transfer function in the working calf muscle and worsened the rate of PCr resynthesis during recovery. The patient reported subjective improvement of general conditions and muscle performance after therapy. Our results indicate that treatment with lipoate caused a relevant increase in levels of energy available in brain and skeletal muscle during exercise."

Jacob S; Henriksen EJ; Schiemann AL; Simon I; Clancy DE; Tritschler HJ; Jung WI; Augustin HJ; Dietze GJ, "Enhancement of glucose disposal in patients with type 2 diabetes by alpha-lipoic acid", Arzneimittelforschung 1995 Aug;45(8):872-4

"Insulin resistance of skeletal muscle glucose uptake is a prominent feature of Type II diabetes (NIDDM); therefore pharmacological interventions should aim to improve insulin sensitivity. Alpha-lipoic acid (CAS 62-46-4, thioctic acid, ALA), a natural occurring compound frequently used for treatment of diabetic polyneuropathy, enhances glucose utilization in various experimental models. To see whether this compound also augments insulin mediated glucose disposal in NIDDM, 13 patients received either ALA (1000 mg/Thioctacid/500 ml NaCl, n = 7) or vehicle only ..Both groups were comparable in age, body-mass index and duration of diabetes and had a similar degree of insulin resistance at baseline. Acute parenteral administration of ALA resulted in a significant increase of insulin-stimulated glucose disposal;.. This is the first clinical study to show that alpha-lipoic acid increases insulin stimulated glucose disposal in NIDDM. The mode of action of ALA and its potential use as an antihyperglycemic agent require further investigation."

Nutrition
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