Lipoic Acid, the 'Antioxidant's Antioxidant'

The power and versatility of this molecule are amazing - 
and probably life-extending

Remember that TV commercial in which, when a certain brokerage company spoke, people listened? Well, when Dr. Lester Packer speaks on the subject of antioxidants, scientists listen. Dr. Packer, a professor of molecular and cell biology at the University of California, Berkeley, and director of the Packer Laboratory there, is one of the world's leading authorities on antioxidants.

So when Dr. Packer says that "Lipoic acid is the most versatile and powerful antioxidant in the entire antioxidant defense network," our ears should perk up. If they listen hard, they might even hear the sounds of our body's cells as they bang their little spoons on the table and cry, "More lipoic acid! More! More!"

Well, suppose we gave it to them. What good would that do? In last month's issue of Life Enhancement, we saw that lipoic acid was beneficial in combating acute mountain sickness in climbers on a Mount Everest expedition. But that was the merest tip of the mountain, so to speak. And since most of us are not mountain climbers anyway, what can lipoic acid do for us? Let us count the ways, as described by Dr. Packer in his recent book, The Antioxidant Miracle (from which most of the information and all the quotations in this article are taken).1

Lipoic acid offers powerful antioxidant protection against three common afflictions (two of them potentially disastrous) associated with aging: stroke, heart attack, and cataracts. It does this by suppressing the action of free radicals in the cells of the brain, heart, and eyes. Free radicals are highly reactive molecules, mostly derived from oxygen, that put our cells under oxidative stress. Think of this stress as a kind of pervasive chemical "pressure" that damages the cells' vital molecules, such as lipids, proteins, and nucleic acids. The resulting deterioration of cellular function is one of the hallmarks of aging.

Lipoic acid has an unusual relationship with four other important antioxidants: glutathione, coenzyme Q10, vitamin C, and vitamin E. Dr. Packer's extensive research has shown that together these five compounds form a unique "antioxidant network": they interact with each other in such a way as to regenerate their antioxidant capacities after they have successfully neutralized free radicals. In other words, they can be used over and over again as antioxidants. Without this regenerative process, these molecules (like most other antioxidants) would be lost to metabolic processes once they had reacted with free radicals. Because lipoic acid is the linchpin in this process - it's the only one that can recycle the other four (and the only one that can do this to itself) - Dr.Packer calls it "the antioxidant's antioxidant."

Memory loss is not considered to be a disease - at least not until it's a component of a full-fledged dementia, such as Alzheimer's disease - but it is certainly another hallmark of aging. As such, it too can be ameliorated by antioxidants such as lipoic acid - particularly lipoic acid, in fact, because this remarkable compound is one of the relatively few antioxidants that can cross the so-called blood/brain barrier and gain direct access to the brain's cells.

Whether you're an athlete or a couch potato, your brain cells are among the hardest working in your body, with insatiable demands for energy. Energy production requires abundant oxygen (as well as glucose, of course), and the resulting oxidation reactions yield an abundance of free radicals. That's the downside of oxygen, which gives life with one hand and takes it, albeit slowly, with the other (but see the sidebar for a different angle on the time scale).

A Lifespan Measured in Minutes?

nlike lipoic acid, other antioxidants are either primarily water-soluble or fat-soluble, but not both. This means that they have different (but often overlapping) domains as free radical scavengers. Most forms of vitamin C, e.g., are water-soluble and patrol our aqueous environments, such as blood and "aqueous humor" - the fluid inside our eyes. Vitamin E is fat-soluble and is characteristically found protecting our cell membranes, which consist primarily of fats (water-soluble vitamin C is of little use there).

The remaining two members of the antioxidant network, glutathione and coenzyme Q10, are found inside our cells near the mitochondrial membranes, where they scarf up the torrents of free radicals produced as the mitochondria convert our food into energy. Without these two vital intracellular antioxidants - particularly glutathione - which our bodies make on their own, the free radicals would overrun our cells like Attila's hordes (a typical cell takes about 20 billion free radical hits per day as it is), attacking and destroying everything in their path.

Our best hope for a long life would then not be about 100 years, but, with luck, about 100 minutes. So much for life enhancement.


Normally - and especially when we're young - the brain's natural antioxidant defense system repels the onslaught of free radicals, minimizing oxidative stress and helping to keep our memory and other faculties sharp. The chief defender here is glutathione, the body's most abundant and most important antioxidant. (Glutathione cannot be taken as a supplement, by the way, because it breaks down in the digestive tract.) As we age, however - and what a familiar refrain this is - the antioxidant system gradually weakens and deteriorates, becoming ever less productive and efficient. The result is . . . uh . . .well, I've forgotten, but I know it's not good.

What is good is that lipoic acid not only acts as a primary antioxidant in brain cells but also serves to boost glutathione levels through the antioxidant network interactions mentioned above. Dr. Packer believes this may be lipoic acid's principal virtue, in fact, because the role of glutathione in maintaining our health - and life itself - is so overwhelmingly important. At any age, low glutathione levels are a biological "marker" for death. These levels are drastically depleted in chronic illnesses such as cancer, autoimmune diseases (e.g., lupus and rheumatoid arthritis), and AIDS.

In Dr. Packer's words, "The fact that lipoic acid can boost glutathione levels so quickly and so well has important application in the prevention and treatment of numerous diseases that afflict human beings. I believe that the practice of medicine in the twenty-first century will focus less on curing disease from the outside with drugs that are foreign to our bodies, and more on empowering the body from within by boosting the disease-fighting powers of the antioxidant network."

Diabetes, a terrible yet largely preventable disease, is practically epidemic in the Western world, especially the United States, because of our tendency to obesity due to poor diet and lack of exercise. In European medical practice, which is typically far ahead of ours in the enlightened use of nutritional supplements, lipoic acid has been used for over two decades to prevent and alleviate the symptoms of diabetes. It does not cure the disease itself, but, in Dr. Packer's words, "it is highly likely that lipoic acid supplements may help prevent the onset of type 2 diabetes in the first place." (Type 2 diabetes is also called age-related diabetes or non-insulin-dependent diabetes.)


 Lipoic acid

Dr. Packer says, "Much of the destruction that is inflicted by this disease is caused either directly or indirectly by free radicals. . . . Diabetes is very much an oxidative stress disease - that is, people who are diabetic have significantly lower levels of antioxidants than normal." One example of the use of lipoic acid in diabetes is for alleviating peripheral neuropathy, a weakening of the muscles caused by damage to the nerves. This common complication of diabetes can be very painful and is directly related to a lack of antioxidants.

Yes, lipoic acid fights age, but it also fights AGE. The latter stands for advanced glycation end products, chemical complexes that result from highly undesirable but all too common reactions between blood sugars, such as glucose, and proteins in many parts of our bodies. These sugar-protein complexes become chemically cross-linked and "gum up the works" in our cells. They are thought to be an important factor in the aging process.

"Lipoic acid is the most 
versatile and powerful 
antioxidant in the entire 
antioxidant defense network."

All people suffer from AGE, especially with advancing age, but diabetics are particularly vulnerable because of their chronically high glucose levels, which hasten the process. Dr. Packer states that lipoic acid helps reduce the damage caused by AGE and can help improve the utilization of glucose by muscle cells. The hemoglobin in our blood is susceptible to becoming "AGEd," as is collagen, the most prevalent structural protein in the body. Collagen is found not only in our bones, skin, and connective tissue, but also in such delicate and vital organs as our eyes and kidneys.

Gene therapy promises to be one of the most exciting and fruitful avenues of medical practice in the twenty-first century. Still in its infancy, gene therapy entails, among other things, the activation of "good" genes and the suppression of "bad" genes through pharmacological intervention. The agents may be synthetic drugs, but they may also be natural products found in our own bodies or in plant or animal sources.

One such intervention is the use of niacinamide, a safe and natural form of vitamin B3, to boost the body's levels of a compound called NAD, which helps suppress the activity of certain genes that are implicated in the aging process.

Another intervention, according to Dr. Packer, is the use of lipoic acid to help suppress the activity of a protein called Nuclear Factor Kappa B, which is known to activate hundreds of different genes. When properly regulated, this remarkable protein can help the body fight disease and perform other critical functions. If it is "turned on" too strongly, however (as can be brought about by free radicals), it can cause problems such as dampening immune function, promoting heart disease, and accelerating the aging of skin. Antioxidants in general, but lipoic acid in particular, are effective in keeping the activity of NF Kappa B under control.

There is still more in lipoic acid's cornucopia of tricks, such as its ability to counteract radiation poisoning (the Russians used it to treat irradiated children after the Chernobyl disaster in 1986) and its use as a cure for the otherwise incurable poisoning caused by the deadly Amanita mushroom. But let us move on to two other questions that may have occurred to you: What is lipoic acid, anyway, and how much of it should we be getting?

Lipoic acid (technically, alpha-lipoic acid, also known as thioctic acid) was first isolated in 1951 and was initially thought to be a vitamin of the B group (it's very similar in structure to biotin). We now know, however, that our bodies synthesize it, so it is not a vitamin. Chemically, lipoic acid (its name comes from the Greek word for fat) is a saturated fatty acid that has an unusual ring structure containing two sulfur atoms at one end of the molecule. Among all the major antioxidants, only lipoic acid has the ability to dissolve in both water and lipids (fatty substances). This means that it can penetrate both the aqueous and lipidic portions of our cells to neutralize the free radicals that are found there - a versatility that is uniquely its own.

Lipoic acid offers powerful 
antioxidant protection against 
three common afflictions 
associated with aging: stroke, 
heart attack, and cataracts.

"Saturated fatty acid" is a term that raises red flags for those who care about their health. But every rule has its exceptions, and lipoic acid is certainly one of them. By now it should be obvious that lipoic acid is a very good saturated fatty acid in many important ways. In every cell of our bodies, e.g., it not only acts as a superantioxidant, it also participates as a vital coenzyme in the Krebs cycle, the complex series of chemical reactions responsible for generating energy through cellular respiration.

Our bodies synthesize lipoic acid in adequate amounts for the Krebs cycle. But are these amounts also adequate for antioxidant activity? "Adequate" and "optimal" can be miles apart, as Linus Pauling and other scientists recognized long ago. Their prescription for closing the gap is supplementation with the nutrients our bodies would love to have more of than they generally get. Which brings us back to our cells' plaintive cries for more lipoic acid. Dr. Packer recommends taking 100 mg per day for its function as a superantioxidant. The tiny supplemental amounts we can get from food - mainly spinach, potatoes, and red meat - are nowhere near adequate for optimal antioxidant activity.

You will be doing every cell in your body a big favor by giving it some lipoic acid.

Next month: A report on new research by Dr. Packer demonstrating the benefits of lipoic acid in reducing oxidative stress, and what that means for your heart in particular.


  1. Packer L, Colman C. The Antioxidant Miracle. John Wiley & Sons, New York, 1999.

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