“The antioxidant’s antioxidant” mimics insulin action and repairs nerve damage

I don’t want to achieve immortality through my work. 
I want to achieve it through not dying.
 — Woody Allen

Made you laugh? Did you know that laughing could lower your blood sugar? No, really! (Stop laughing.) Japanese researchers reported recently that people who laughed after a meal had lower blood sugar levels than people who didn’t laugh. They don’t know why, but it must be one of those mind-over-matter deals. Maybe Woody Allen knows.

So eat (sensibly), drink (in moderation), and try to be merry! Lord knows, we need all the laughs we can get these days, what with the war on terror, the political mudslinging, and a children’s book written by Madonna. As if all that weren’t bad enough, epidemiologists are warning that diabetes threatens to become the greatest worldwide public health crisis of the twenty-first century, dwarfing AIDS in its social and economic impact. Diabetes is a leading cause of kidney failure and blindness and is a gateway to many other afflictions, including heart attacks and strokes, which are about two to four times as likely to occur in diabetics as in nondiabetics.

Diabetes Is Becoming a Pandemic

The experts predict that by 2025 the number of people with diabetes—mainly type 2, or adult-onset, diabetes (which accounts for up to 95% of all cases in the USA)—will balloon from the current 194 million to 333 million worldwide.1 The cost to society will be staggering: between $213 billion and $396 billion, according to some estimates. The disease is already killing about 100 million people a year.

The pandemic is expected to hit hardest in developing countries, for various reasons. Americans should take no comfort in that prediction, however, because diabetes is already epidemic in the United States—the obesity capital of the world—where it is the seventh leading cause of death. (See the sidebar “What’s the Risk?”) An estimated 15 million people have it, and about half of them don’t even know it. Millions more are on the fat track to diabetes.

What’s the Risk?

Here are some stark figures. It is estimated that the number of diagnosed cases of diabetes in the United States will increase by 165% during the next half-century, with the fastest increases occurring in older and minority populations. According to a new statistical analysis, for individuals born in 2000, the estimated lifetime risk of developing diabetes is 33% for males and 39% for females (who are at somewhat higher risk than males at all ages).1

Those who do develop the disease will have large reductions in life expectancy. For example, a man diagnosed at age 40 will likely lose 12 years of his life (19 years in terms of so-called quality-adjusted life-years, or QALY), compared with a man who does not get the disease, and a woman diagnosed at that same age will likely lose 14 years of her life (22 QALY).

Part of the reason for the high lifetime risks of developing diabetes is the shocking rise in its incidence among younger people nowadays—not just young adults, but even young children, owing to their atrocious junk-food diets and lack of exercise. The study’s authors estimated that, on average, boys diagnosed with diabetes at age 10 will lose 19 years of life (31 QALY), and girls will lose 19 years of life (33 QALY).

How incredibly sad—and how easily preventable.

  1. Narayan KMV, Boyle JP, Thompson TJ, Sorensen SW, Williamson DF. Lifetime risk for diabetes mellitus in the United States. JAMA 2003 Oct 8;290(14):1884-90.

Obesity Leads to Insulin Resistance and the Metabolic Syndrome

That was not a misprint in the previous sentence. As a people, we are exceedingly fat, and part of the price we’re paying for it is type 2 diabetes, which is caused almost exclusively by that one factor. With obesity often comes the insidious condition of insulin resistance, the tendency for our cells to resist this vital hormone’s normal—and critical—function. (Insulin resistance is also age-related.) That function is to facilitate the transport of glucose (blood sugar) through the cell walls into the interior, where it becomes the primary fuel molecule for powering all of our life processes.

Thus, obesity-driven insulin resistance leads to increased blood sugar levels, which over the long term are extremely damaging to our health. At the same time, obesity also typically leads to high cholesterol and triglyceride (fat) levels, and to high blood pressure. Together these factors constitute a nasty condition called the metabolic syndrome (sometimes called syndrome X in the popular literature), which is a steppingstone to diabetes, heart disease, and potentially to stroke, kidney failure, and cancer (particularly colon cancer) as well.* It is a major threat to public health in the United States and throughout the world.

*The form of obesity most strongly linked to these degenerative diseases is abdominal obesity—a pronounced bulge in the midriff. So if you have a potbelly, think of it as something that could kill you. That should motivate you to get rid of it.

Lipoic Acid—The Antioxidant’s Antioxidant

So what’s the solution to the diabetes crisis? For most people (i.e., those who don’t have a genetic predisposition to diabetes), it’s incredibly simple: avoid obesity. (See the sidebar “How Fat Is Obese?”) That means diet and exercise, the Dynamic Duo of good health. But for those whose good intentions are paving their personal road to Hell and who don’t want to become dependent on expensive pharmaceuticals, there are safe and effective nutritional supplements that can help them get onto the road to better Health. One such supplement is the powerful and versatile antioxidant lipoic acid (also called alpha-lipoic acid, and sometimes thioctic acid).

How Fat Is Obese?

Obesity is being way too fat—we all know that. A better definition is being more than 20% above the normal, desirable weight for one’s height. Probably the best definition of obesity is having a body-fat percentage greater than 25%, for men, or greater than 30%, for women. (Oddly, feminists are not complaining about this double standard.)

A common measure of obesity is body mass index (BMI), which provides a rough measure of health and life expectancy. To calculate your BMI, divide your weight in pounds by the square of your height in inches, and multiply the result by 703. (In metric units, divide your weight in kilograms by the square of your height in meters.) The ideal range is about 19–22, but 23–24 is still good. A value in the 25–29 range indicates that you’re overweight—a moderate threat to your health and longevity. If your BMI is 30 or more, you’re obese, and you’re at serious risk of life-threatening diseases.

Yet another window on obesity is your waist/hip ratio (WHR), which gives an indication of where you’re carrying excess fat. Too much around the middle is a definite risk factor for disease or disability. Measure your waist, measure your hips at the widest point, and then divide the waist by the hips. Men should have a WHR of less than 1.0; for women, it should be less than 0.8.

Lipoic acid is one hell of a supplement, if you’ll forgive the expression. This stems from its unique role as the linchpin in the body’s so-called antioxidant network, a web of mutually beneficial chemical interactions among five of the most important antioxidant molecules known: vitamin C, vitamin E, coenzyme Q10, glutathione, and . . . lipoic acid. Lipoic acid is called “the antioxidant’s antioxidant” because of the key role that it plays in regenerating the other four.

Lipoic Acid Is Astonishingly Versatile

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.

One of the world’s leading antioxidant researchers is Dr. Lester Packer, a professor of molecular and cell biology at the University of California, Berkeley. In his book The Antioxidant Miracle, he discusses the varied benefits of lipoic acid (among other antioxidants) at length.2 Among other things, lipoic acid:

  • Helps protect us from diseases of aging and some of their dire consequences—most notably cardiovascular disease (heart attack), cerebrovascular disease (stroke), and cataracts (blindness).
  • Helps inhibit age-related memory loss, a function it performs particularly well because it’s one of the relatively few antioxidants that can cross the blood/brain barrier and gain direct access to the brain’s cells.
  • Boosts glutathione levels through the antioxidant network interactions mentioned above. This may be lipoic acid’s principal virtue, in fact, because the role of glutathione in maintaining our health—and our life—is so overwhelmingly important.
  • Helps regulate the activity of a beneficial disease-fighting protein called nuclear factor kappa B that, when it becomes overactive (through oxidative stress, e.g.), can cause problems such as suppressing immune function, promoting heart disease, and accelerating the aging of skin.
  • Helps reduce the damage caused by AGE, which stands for advanced glycation end products. These are deleterious molecular complexes resulting from chemical reactions between blood sugars and proteins in many vital parts of our bodies, such as the blood, bones, skin, connective tissue, kidneys, and eyes. AGE formation is thought to be an important factor in the aging process.

All people suffer from AGE, but some are particularly vulnerable because of their chronically high glucose levels, which hasten the process. Those people are, of course, diabetics (or prediabetics). And that brings us to the role of lipoic acid in diabetes itself.

Lipoic Acid Seems to Mimic Insulin’s Action

In European medical practice (which is in some ways far ahead of ours in the enlightened use of nutritional supplements, although the politics of nutrients in Europe is bizarre), lipoic acid has been used for over two decades to prevent and alleviate the symptoms of diabetes. It is known, e.g., to improve glucose metabolism3 and increase insulin sensitivity4 in diabetic patients; it also enhances glucose transport into rat skeletal muscle cells5 and into mouse fat cells.6

In these regards, lipoic acid seems to mimic the functions of insulin. That’s a neat biochemical trick, for which a remarkable molecule found in cinnamon, called MHCP(methylhydroxychalcone polymer), is also known; MHCP and lipoic acid probably do not act via the same mechanism, however.

Lipoic acid does not cure diabetes, 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.” He goes on to say, “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.”

The response to the treatment was 
very good or good in 67% of the 
lipoic acid group, compared with 
only 2% in the control group.

One example of the use of lipoic acid in treating diabetes is for diabetic neuropathy, a term that means functional disturbances in the extremities (usually the legs) caused by damage to the nerves. Since chronic elevation of blood sugar levels is one cause of such damage, neuropathy is common in later stages of type 2 diabetes. It usually manifests as either pain (stabbing, burning, aching, etc.) or a loss of sensation, depending on the nature and extent of the damage.

Lipoic Acid Improves Damaged Nerves

In a randomized, placebo-controlled, double-blind study conducted recently by a team of researchers from the United States, Russia, Germany, and Croatia, 120 adult patients (average age 56) suffering from painful diabetic neuropathy were given lipoic acid or placebo intravenously (600 mg/day) 14 times over a 3-week period (it’s not clear why it was not given orally).7 Lipoic acid was chosen because of its known efficacy and extremely low toxicity, and its extensive use in medical practice, including oral diabetes therapy, in Europe.

By the fourth day of treatment, the patients receiving lipoic acid began feeling significantly better (as measured by a standard pain index called the Total Symptoms Score) than those on placebo, and this gap in the results continued to widen thereafter. After 3 weeks, the evaluating physician rated the response to the treatment as very good or good in 67% of the lipoic acid group, compared with only 2% in the control group. The figures for a rating of satisfactory were 33% and 68% for these two groups, respectively, and the remainder of the control group had ratings of unsatisfactory (27%) or not assessable (3%).

These figures attest to the antioxidant power of lipoic acid, which the researchers believe is the source of its beneficial effect on neuropathy. In other words, lipoic acid was acting not as a painkiller (which it isn’t) but as a therapeutic agent in improving the pathophysiology of the damaged nerves. The researchers stated:

The present study appears to show an unequivocal and large beneficial effect of intravenous racemic alpha-lipoic acid on the frequency and severity of the positive neuropathic sensory symptoms due to diabetic polyneuropathy . . . .

(“Racemic” refers to an equal mixture of two different forms of lipoic acid). Beneath the technical jargon, the researchers are saying that lipoic acid is very helpful to diabetics suffering from the pain caused by nerve damage. That’s something to cheer about!

What’s So Funny?

So don’t forget to take your lipoic acid supplement. The tiny amounts you get at dinnertime—mainly from spinach, potatoes, and red meat—aren’t nearly adequate for optimal antioxidant activity. And to help keep your blood sugar in check, remember to laugh after dinner.

A priest and a rabbi go into a biker bar . . . .


  1. Sithole E. World facing diabetes catastrophe: experts. Reuters Health report, Paris, Aug. 25, 2003.
  2. Packer L, Colman C. The Antioxidant Miracle. John Wiley & Sons, New York, 1999.
  3. 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;45(8):872-4.
  4. Jacob S, Ruus P, Hermann R, Tritschler HJ, Maerker E, Renn W, Augustin HJ, Dietze GJ, Rett K. Oral administration of rac-alpha-lipoic acid modulates insulin sensitivity in patients with type 2 diabetes mellitus: a placebo-controlled pilot trial. Free Rad Biol Med 1999;27(3/4):309-14.
  5. Henriksen EJ, Jacob S, Streeper RS, Fogt DL, Hokama JY, Tritschler HJ. Stimulation by alpha-lipoic acid of glucose transport activity in skeletal muscle of lean and obese Zucker rats. Life Sci 1997;61(8):805-12.
  6. Cho K-J, Moini H, Shon H-K, Chung A-S, Packer L. A-Lipoic acid decreases thiol reactivity of the insulin receptor and protein tyrosine phosphatase 1B in 3T3-L1 adipocytes. Biochem Pharmacol 2003;66:849-58.
  7. The Sydney Trial Authors, for the Sydney Trial Study Group: Ametov AS, Barinov A, Dyck PJ, et al. The sensory symptoms of diabetic polyneuropathy are improved with A-lipoic acid: the Sydney Trial. Diabetes Care 2003 Mar;26(3):770-6.