The Power of Lipoic Acid
The “antioxidant’s antioxidant” protects a
molecule that plays a key role in sexual function
By Richard P. Huemer, M.D.
Time was when every American boy looked forward to getting an Erector Set for Christmas or his birthday. One Hollywood star, however (a certain aging screen idol), had to wait longer than usual for his. When he entered into a May-December marriage, his best friend, a comedian, waggishly sent him an Erector Set as a wedding gift.
No doubt the prank elicited some knowing smiles and chuckles among the wedding guests. But impotence is no laughing matter. Also called erectile dysfunction, it may affect as many as 30 million American men. Its incidence increases with age. By one estimate, over half of men between the ages of 40 and 70 have it to some degree, ranging from minimal to severe.
It’s Not All in Your Head
Impotence used to be considered a psychosomatic disorder, but doctors now believe that most cases, perhaps 70%, have organic roots. Some cases arise from physical trauma, such as spinal injury or injury to the penile artery from bike riding. Others are due to drugs, both recreational and therapeutic (the main offenders in the latter category are antihypertensives and antidepressants). Most impotence, however, arises from neurologic, vascular, and metabolic diseases.
Listing the diseases that can cause impotence is like compiling a list of the 10 most wanted criminals, except that this is a list of the least wanted. In the neurologic category, there are strokes, multiple sclerosis, and Parkinsonism; in the vascular category, hypertension, atherosclerosis, and heart disease; and in the metabolic category, alcoholism, kidney failure, hormone deficiencies, and diabetes.
Diabetes Is a Major Risk Factor
An estimated 30 to 50% of diabetic men are afflicted with impotence. The reason is that diabetes entails widespread vascular and neurological damage. This impairs the ability to achieve and maintain an erection, which requires healthy blood vessels and nerves. Damage to blood vessels can also lead to such disparate outcomes as stroke, heart attack, hypertension, kidney failure, blindness, and gangrenous digits that may ultimately require amputation.
Nerve damage in diabetes usually manifests as polyneuropathy, which is a nontraumatic, generalized disorder of peripheral nerves that is due partly to poor blood circulation. It usually begins at the outermost extremities and can entail pain, burning, paresthesia (a prickling or tingling sensation), and numbness. That’s bad enough, but nerve damage in diabetes can even interfere with heart function.
Some of the complications of diabetes are caused by the disease’s sharp acceleration of a degenerative process that already occurs to some extent as a normal part of aging. It’s a chemical process called glycation, which degrades many kinds of proteins throughout the body—in the blood and in organs such as the skin, kidneys, and eyes. (See the article on page 24 of this issue for how glycation leads to cataracts.)
Lipoic Acid—Linchpin Antioxidant
Following your doctor’s orders regarding diet, exercise, and medication is the best way to control diabetic complications, but sometimes more help is useful, in the form of nutritional supplements. It has long been known that lipoic acid, a sulfur-containing saturated fatty acid, is an effective treatment for diabetic polyneuropathy. At least, this has been known to most European doctors, and lipoic acid is approved in Germany as a drug for treating this condition. The American medical community has, however, remained largely unaware of (or uninterested in) lipoic acid’s many health benefits.
There are good reasons to suppose that lipoic acid (aka alpha-lipoic acid or thioctic acid) should be effective not just against polyneuropathy but also against a wide array of other diabetic complications. Lipoic acid is a powerful antioxidant, one of five members of the body’s vital antioxidant network, the other four being glutathione, coenzyme Q10, and vitamins C and E. These antioxidants have the capacity for regenerating each other (to varying degrees) after they’ve reacted with pro-oxidants, such as free radicals. Because lipoic acid plays the central role in this interactive network, it is known as the “antioxidant’s antioxidant.”
Lipoic Acid Mitigates Diabetic Complications …
That term was coined by the world’s leading antioxidant researcher, Lester Packer, who has said, “Available data strongly suggest that lipoic acid, because of its antioxidant properties, is particularly suited to the prevention and/or treatment of diabetic complications that arise from an overproduction of reactive oxygen and nitrogen species.” In other words, oxidative chemical reactions run rampant in the diabetic body; these reactions cause complications attributable to the disease; and they can be mitigated by lipoic acid.
Dr. Packer and his colleagues have cited abundant evidence that diabetic patients show increased amounts of oxidative damage to lipids (fats and fatty substances) and DNA; perhaps not surprisingly, these patients have reduced levels of protective antioxidants.The chemical chaos comes from high glucose (blood sugar)—a hallmark of diabetes—which leads to glycation and the formation of destructive free radicals. The authors cited experimental and clinical studies showing that lipoic acid “markedly reduced the symptoms of diabetic pathologies, including cataract formation, vascular damage, and polyneuropathy,” as well as a study showing that it inhibits protein glycation. (For more on these matters, see “Lipoic Acid, the ‘Antioxidant’s Antioxidant’” in the July 2001 issue.)
. . . Including Impotence (in Lab Experiments)
If lipoic acid can do all that, could it also alleviate impotence? The answer may be yes, based, at least, on laboratory studies conducted by researchers at the University of Aberdeen in Scotland. Their aim was to determine the effects of diabetes and long-term lipoic acid treatment on vascular and neurological function in the penises of diabetic rats. In contrast to humans, who usually require years of wretched eating habits and lack of exercise to acquire type 2 diabetes, rats can be made diabetic overnight by a single injection of the drug streptozotocin.
The researchers did that, and they treated the diabetic rats with lipoic acid—some for 8 weeks starting immediately, and some only for the last 4 of those 8 weeks. When they killed the rats after 8 weeks, they dissected the penises to isolate the corpora cavernosa, the two parallel columns of spongelike erectile tissue, whose engorgement with blood causes an erection (in a sense, it is the erection). After using a drug, phenylephrine, to cause the cavernosal tissue to contract, the researchers administered acetylcholine to induce its relaxation (which, in real life, is necessary for erection to occur).
Relaxation of the tissue was 41% less in untreated diabetic rats than in normal, nondiabetic rats. In the diabetic rats that had been treated with lipoic acid for the full 8 weeks, however, this deficit was prevented with 94% efficiency. In the group that had been treated only for the last 4 weeks of the diabetic period, the deficit was corrected with 65% efficiency. The authors stated,
The antioxidant lipoic acid provided a high level of protection and partially reversed an established defect. This is the first report of successful treatment of impaired corpus cavernosum endothelial responses [impotence] in experimental diabetes.
No NO? Lipoic Acid Can Help
The “endothelial responses” they alluded to, and the molecule involved, are the crux of the matter. The endothelium is the layer of smooth, flat cells that line the inner walls of our blood vessels, including the penile arteries. Endothelial cells are partly responsible for inducing the arteries to relax (dilate) when needed, such as when an erection is desired. This effect is mediated by nitric oxide, a very simple but potent molecule whose formula is NO (one atom each of nitrogen and oxygen). NO is generated in our cells from the amino acid arginine by a chemical reaction catalyzed by the enzyme endothelial nitric oxide synthase (eNOS).
In related experiments, the authors showed that the relaxation of cavernosal tissue is also brought about in part by neurons of the nitrergic nervous system. The principal neurotransmitter for these neurons is NO, and the reaction that produces it is catalyzed by the enzyme neuronal nitric oxide synthase (nNOS). (For more on NO, see the sidebar “Will the Real Erectile Molecule Please Stand Up?”)
Will the Real Erectile Molecule Please Stand Up?
Scientists understood in considerable detail how babies develop from fertilized eggs more than a century before they had a full explanation of a critical process that immediately precedes fertilization. Nobody knew until fairly recently that a simple gaseous molecule, nitric oxide, was necessary for penile erection, because nobody had any inkling of the existence of the nitrergic nervous system, in which NO is the neurotransmitter. Scientists believed that the well known adrenergic (noradrenaline-based) and cholinergic (acetylcholine-based) nervous systems were the whole story when it came to erections.
Now we know that nitrergic nerves join those other nerves in instant-messaging a male’s nether region and that these stimuli, along with NO originating within the endothelium of the penile arteries, dilate the arteries and relax smooth muscle tissue in the corpora cavernosa. The corpora expand as they fill with blood from the dilated arteries, and erection is maintained for as long as the turgidity of the corpora shuts off the venous outflow from the penis by compressing the veins.
It’s worth noting that the well-known impotence drugs all act by inhibiting an enzyme, phosphodiesterase-5, that interferes, in a roundabout way, with NO activity. It’s also worth noting that in July 2005, these three drugs were the subject of an FDA warning regarding the possibility of sudden blindness as a result of ischemic optic neuropathy (damage to the optic nerve caused by impaired blood flow).
We think that the natural approach to sex is best, and clearly, NO news is good news. Considering the unique importance of this vital compound to mankind’s favorite pastime, we propose renaming the molecule YES, but we realize we’re bucking long-established chemical tradition here.
To say that NO molecules are important for erections would be hard to dispute. NO function is impaired in diabetes, and the authors suggested that this may be due not to decreased levels of the NOS enzymes (a controversial matter), but rather to reduced activity of NO itself, caused by reactive oxygen species, such as free radicals. (Ironically, NO is itself a free radical.) The strong protective action of the antioxidant lipoic acid therefore makes sense.
There’s More to Lipoic Acid than Sex
Whether or not the findings on lipoic acid’s possible value in impotence will, um, measure up is anyone’s guess. We do not know if any clinical studies are in the works, but a reasonable approach would be to quantify nocturnal penile tumescence (erections occurring during sleep) under controlled conditions, with and without lipoic acid. A null outcome seems unlikely, in view of lipoic acid’s other known benefits in diabetes and for good health in general.
Those benefits include the aforementioned neurovascular, antioxidant, and antiglycation effects, and more: increasing insulin sensitivity, improving glucose metabolism, boosting levels of the antioxidant glutathione, and inhibiting the activation of a proinflammatory protein called NF-kappaB. Lipoic acid helps inhibit age-related memory loss, improves the senses of taste and smell, and boosts immunity. Although it is made naturally in healthy bodies, supplementation with this remarkable compound becomes more beneficial with age, especially in the presence of diseases, such as diabetes, that deplete its natural levels.
Laughter + Love = Longevity
By the way, the comedian who presented his pal with the Erector Set lived to a ripe old age. Some of his longevity must surely be attributable to laughter, which has a positive impact on health. As we reported in these pages, it can even lower your blood sugar (see “Lipoic Acid Helps Fight Diabetes,” December 2003). By extension, the joys of successful coitus might add to the duration of life as well as to its quality.
- Packer L, Kraemer K, Rimbach G. Molecular aspects of lipoic acid in the prevention of diabetes complications. Nutrition 2001;17:888-95.
- Keegan A, Cotter MA, Cameron NE. Effects of diabetes and treatment with the antioxidant alpha-lipoic acid on endothelial and neurogenic responses of corpus cavernosum in rats. Diabetologia 1999;42:343-50.
- Roy P, Venkat Ramana G, Naidu MU, Usha Rani P. Recent trends in the nitrergic nervous system. Indian J Pharmacol 2005;37:69-76.
The Human Faces of Diabetes
Onward they march toward an early grave—a brigade of the blind, halt, and lame, whose ranks swell daily with ever younger recruits: victims and would-be victors of the diabetes epidemic. Over 90% of them have type 2 diabetes, which used to be called adult-onset diabetes before so many children started showing up with it. Genetics is a factor in some cases, but genes don’t evolve fast enough to explain the burgeoning epidemic. The primary culprit is our supersized fast-food meals of refined carbohydrates and fats, together with our couch-potato lifestyle.
The human cost is heartbreaking: here, a 10-year-old with a blood sugar of 400; there, a middle-aged woman who’s had a mild stroke and is blind in one eye; over there, a man on dialysis whose foot has been amputated. A New York endocrinologist predicted the likely condition of the American workforce in 50 years, if things don’t change: “fat, one-legged, and blind.”
Diabetes is the main cause of blindness in adults, not only because of cataracts but also because of retinopathy (pathological changes in blood vessels in the retina). The only treatments are laser surgery and drugs injected into the eyeball.
One middle-aged woman, whom we’ll call Cecelia M, has had overt diabetes for 10 years. A vision specialist by profession, she was slowly going blind from retinopathy. After starting a nutritional supplement program that included 1000 mg of lipoic acid daily, she got good news from her laser surgeon: “Keep up whatever you’re doing, because the degeneration has slowed way down.” She doesn’t know which element of a complex program may have helped her, so she doesn’t dare quit any of her supplements.
Caution: If you have diabetes, do not take any supplement that may affect your blood sugar levels without first consulting your physician. Diabetes is a serious disease requiring careful professional management.
Dr. Richard P. Huemer received his M.D. from UCLA and did postdoctoral research in cancer immunology at CalTech. He has specialized in orthomolecular medicine for most of his career, has written and lectured extensively on alternative medicine, and has served on the editorial boards of professional journals. His published books include The Roots of Molecular Medicine: A Tribute to Linus Pauling and, with coauthor Jack Challem, The Natural Health Guide to Beating the Supergerms.