By Benjamin V. Treadwell, Ph.D.

Alpha lipoic acid (ALA) is a vitamin-like nutrient that is essential for life. The conversion of food to energy within our cells derives predominantly from a series of reactions within the mitochondria, commonly referred to as the Krebs Cycle. Alpha Lipoic Acid acts like a catalytic converter for the reactions that involve two key enzyme complexes, without which the Cycle would shut down and the cell would die. (For more information visit the following articles Alpha Lipoic Acid: A Marvelous Nutrient, and The Two Faces of Alpha Lipoic Acid.)

Although this conversion of food to energy is its primary function, recent studies have shown that Alpha Lipoic Acid may also be effective in treating many chronic health problems.

Cell culture and animal research, along with human clinical trials and anecdotal evidence, seem to support Alpha Lipoic Acid's therapeutic value for migraine headache, macular degeneration, obesity, inflammation, cataracts, multiple sclerosis, neurodegenerative, cardiovascular and liver disease, and, in particular, type II diabetes.

ALA The Cell Protector
Pain, numbness, tingling, burning sensations.. .the exact mechanism by which Alpha Lipoic Acid lessens these diabetic symptoms is not yet known. However, results from recent cell culture and animal studies appear to provide some exciting clues.

A study examining the effects of Alpha Lipoic Acid on preventing the death of liver cells, after exposure to a death-promoting inflammatory substance produced by the cell (TNF alpha), demonstrated a new function for Alpha Lipoic Acid: the ability to bind to a specific area (tyrosine kinase domain) of the insulin receptor, which results in its activation. Once activated, the receptor initiates a series of reactions forming a biochemical pathway (PI3-K/Akt pathway) in the cell that acts to counter the TNF alpha-induced death pathway.

The investigators also noted that the PI3-K/Akt pathway, although primary, was not the only cell-saving mechanism. Their results indicated that the antioxidant property associated with Alpha Lipoic Acid (ALA) plays some role in preventing cellular death as well. Moreover, only ALA, and not other antioxidants, binds to the insulin receptor and activates the life-saving PI3-K/Akt pathway.

Less Cellular Stress
These results provide valuable insight into how ALA may function to improve the symptoms of diabetic neuropathies and increase insulin receptor sensitivity.

Animal studies of tissue under diabetic conditions have also demonstrated how cellular stress is produced by increased oxidative stress. Similar to what happened in the liver cell study, this stress promotes inflammation and the production of inflammatory substances like TNF alpha. The end-result is damage to nerve tissues and eventual death of some nervous system cells.

Translation: The painful condition of the peripheral nervous system experienced by diabetic patients may be partially caused by this inflammation-induced damage. ALA may neutralize the inflammatory pathway via binding to the insulin receptor which activates the PI3-K/Akt, or pro-survival, pathway.

As to increased insulin sensitivity and its glucose regulating benefits, this, too, seems to be a result of ALA's ability to support insulin in activating the receptor. You might say that ALA converts a rusty non-compliant insulin receptor to a hair-trigger receptor that is more easily set-off, i.e., activated, in response to insulin.

ALA and Us
Recent human clinical trials seem to support cell culture and animal study findings. Patients with certain nervous system pathologies associated with type II diabetes have experienced significant improvement from taking ALA in oral doses (600 mg/day). Clinical trials also indicate that ALA does improve insulin sensitivity.

Whether the actual mechanisms responsible for the positive effects in humans are explained by the results obtained from animal and cell culture studies remains to be determined. However, it is clear from these and other studies on ALA that additional research on this vitamin-like compound is warranted.

Twelve German, Russian, American and Israeli researchers recently conducted a multicenter, double-blind, placebo-controlled clinical trial to examine the effects of alpha lipoic acid (ALA) on neuropathic symptoms in type II diabetic patients. The summary of their methods, findings and conclusions can be found in the November, 2006, issue of Diabetes Care.

During the trial, 181 patients in Russia and Israel received daily oral doses of ALA or a placebo for five weeks. The primary outcome measure was the change from baseline of the Total Symptom Score (TSS), including measurements of stabbing pain, burning pain, paresthesia (tingling or pricking), and numbness of the feet.

In addition to demonstrating an improvement in TSS with ALA doses of 600 mg to 1800 mg per day, the research also identified 600 mg as the dose with the optimum risk-to-benefit ratio. The authors make note of a low incidence of side effects.

To read the abstract, click here.
"Oral Treatment With alpha-Lipoic Acid Improves Symptomatic Diabetic Polyneuropathy."
Diabetes Care 29:2365-2370, 2006.

This Research Update column highlights articles related to recent scientific inquiry into the process of human aging. It is not intended to promote any specific ingredient, regimen, or use and should not be construed as evidence of the safety, effectiveness, or intended uses of the Juvenon product. The Juvenon label should be consulted for intended uses and appropriate directions for use of the product.

QUESTION: How does Juvenon™ Cellular Health Supplement affect blood pressure, if at all? — J.P.

ANSWER: Juvenon has little or no effect on normal people with normal blood pressure. However, for those with mild hypertension, Juvenon does appear to have a slight but positive effect. A recent study, demonstrating the effect of the Juvenon supplement on mildly hypertensive patients, is being published in the Journal of Clinical Hypertension, vol.9, pp 249-255 (2007).

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Benjamin V. Treadwell, Ph.D., is a former Harvard Medical School associate professor and member of Juvenon's Scientific Advisory Board.