Findings from Scientists from the Linus Pauling Institute

The evidence suggests that Lipoic Acid is actually a low-level stressor that turns on the basic cellular defenses of the body, including some of those that naturally decline with age,” said Tory Hagen, an LPI researcher and associate professor of biochemistry and biophysics at OSU. “In particular, it tends to restore levels of glutathione, a protective antioxidant and detoxification compound, to those of a young animal.”

Researchers at LPI are studying vitamins, dietary approaches and micro-nutrients that may be implicated in the aging or degenerative disease process and say that Lipoic Acid appears to be one of those with the most compelling promise.

According to Hagen, research on the natural processes of aging, and steps that could slow it or improve health until near the end of life, are of growing importance.

“We’re coming into the middle of an aging epidemic in the country,” he said. “In a short time more than 70 million Americans will be over 65. This is partly because of the Baby Boom, but also people are living longer, being saved with antibiotics and other medical treatments. In any
case, it will be an unprecedented number of elderly people in this nation.

The goal of LPI research, Hagen said is to address issues of “healthspan,” not just lifespan – meaning the ability to live a long life with comparatively good health and vigor, free of degenerative disease, until very near death. The best mechanisms to accomplish that, scientists
say, have everything to do with diet, exercise, healthy lifestyle habits and micro-nutrient intake.

At the moment, Hagen said, that’s not the way things appear to be headed – diabetes is skyrocketing, about 50 percent of people over 65 have high blood pressure, heart disease often leads to permanent disability, and almost half of the elderly people in America have malnutrition that is easily preventable.

No single intervention can address all of these issues, Hagen said, but one that scientists keep coming back to is Lipoic Acid.

“Our studies have shown that mice supplemented with Lipoic Acid have a cognitive ability, behavior, and genetic expression of almost 100 detoxification and antioxidant genes that are comparable to that of young animals,” Hagen said. “They aren’t just living longer, they are living
better – and that’s the goal we’re after.”

What the OSU researchers now believe is that the role of Lipoic Acid is not so much a direct one to benefit cells, but rather an indirect aid that “kick starts” declining function in cells and helps them recover the functions that came more easily and naturally in young animals.

In various effects, Lipoic Acid appears to help restore a cellular “signaling” process that tends to break down in older blood vessels. It reduces mitochondrial decay in cells, which is closely linked to the symptoms of aging. With age, glutathione levels naturally decline, making older animals more susceptible to both free radicals and other environmental toxins – but Lipoic Acid can restore glutathione function to near normal. And the expression and function of other genes seems to come back to life.

“We never really expected such a surprising range of benefits from one compound,” Hagen said. “This is really unprecedented, and we’re pretty excited about it.”

Lipoic Acid could help reduce atherosclerosis, weight gain

A new study done with mice has discovered that supplements of Lipoic Acid can inhibit formation of arterial lesions, lower triglycerides, and reduce blood vessel inflammation and weight gain – all key issues for addressing cardiovascular disease.

Although the results cannot be directly extrapolated beyond the laboratory, researchers report that “they strongly suggest that Lipoic Acid supplementation may be useful as an inexpensive but effective intervention strategy . . . reducing known risk factors for the development of atherosclerosis and other inflammatory vascular diseases in humans.

Heart disease is the leading cause of death in the United States

The study found that Lipoic Acid supplements reduced atherosclerotic lesion formation in two types of mice that are widely used to study cardiovascular disease, by 55 percent and 40 percent, respectively. The supplements were also associated with almost 40 percent less body weight gain, and lower levels of triglycerides in very low-density lipoproteins.

As a result, the authors concluded that “Lipoic Acid may be a useful adjunct in the prevention and treatment of atherosclerotic vascular diseases.” “We are excited about these results, particularly since the supplements of Lipoic Acid appear to provide several different mechanisms to improve cardiovascular health,” said Balz Frei, professor and director of the Linus Pauling Institute. “They are helping in a fundamental way to reset and normalize metabolic processes, in ways that could help address one of the most significant health problems in the Western world.

“These findings also reinforce the need for more comprehensive human studies,” Frei said. “That will be the next step in our research, in double-blind, randomized, clinical studies during the next five years with Oregon Health and Science University.”

Alpha Lipoic Acid is a naturally occurring nutrient found at low levels in green leafy vegetables,
potatoes and meats, especially organ meats such as kidney, heart or liver. The amounts used in this research would not be obtainable by any normal diet, researchers said, and for human consumption might equate to supplements of about 2,000 milligrams per day. Even at low, normal, dietary levels, the compound can play a key role in energy metabolism.

Atherosclerosis, or what used to be called “hardening of the arteries,” is a long-term process that
is now seen as a chronic inflammatory disease, which begins when certain types of white blood
cells called monocytes bind to “adhesion molecules” on the walls of arteries. This in turn allows
the monocytes to enter the arterial wall, there they become inflammatory macrophages that, in
the presence of low density lipoprotein, or LDL, can transform into lipid-laden foam cells –
ultimately, an arterial fat deposit.

This chronic process often begins during adolescence, can continue for a lifetime, and has been
linked to obesity, poor diet, lack of exercise, diabetes, high blood pressure, genetic predisposition
and other causes. The fatty deposits in arteries can ultimately trigger a heart attack or stroke

Researchers now believe that high levels of Alpha Lipoic Acid can be particularly useful in
preventing this process, by inhibiting the formation of the adhesion molecules. It can also lower
triglycerides, another important risk factor for cardiovascular disease. It may also function as an
antioxidant, and helps to normalize insulin signaling and glucose metabolism.

“From what we understand, this supplement would be most valuable as a preventive mechanism
before people have advanced cardiovascular disease,” Frei said. “However, it may help retard the
process at any stage, and may also be of value in treating diabetic complications.”

Also of considerable interest, Frei said, is the apparent role of Lipoic Acid supplementation in
reducing weight gain. It appears to have this effect both through appetite suppression, an
enhanced metabolic rate, and – at least in laboratory animals – has been shown to stimulate
higher levels of physical activity, which again would increase caloric expenditure and further
reduce weight.

Mice given Lipoic Acid supplements simply chose to eat less than a control group that did not
receive supplements, suggesting a reduced appetite. In another test, mice that received
supplements gained less weight than other mice in a control group that were given identical
amounts to eat, suggesting a higher metabolic rate and enhanced activity levels.

Weight gain and obesity is a major risk factor for atherosclerosis and heart disease, and lower
weight and abdominal fat may be one of the mechanisms by which Lipoic Acid has beneficial
effects, Frei said. The study concluded that “Lipoic Acid supplementation may be a promising
approach to prevent weight gain and to lower cardiovascular disease risk in humans.”

Although some of the most compelling research with Lipoic Acid research has been done in
mouse models, scientists say, there should be a reasonable extrapolation to humans, because the lipoprotein profile is similar, as well as the composition of the atherosclerotic lesions. These
mouse models are routinely used in studies of human atherosclerosis

Only 4 out of 40 Antioxidants Are Any Use: Lipoic Acid is One of the Four

First the good news: a study by scientists at the Buck Institute for Age Research shows four common antioxidants extended lifespan in the nematode worm C. elegans. And the not such good news: those four were among 40 antioxidants tested, the majority of which did nothing or caused harm to the microscopic worms. The findings highlight the complexity of biological processes involved in aging and sends a cautionary signal to consumers who take antioxidants assuming the supplements will help them live longer, healthier lives. Results of the study now appear in the online edition of Experimental Gerontology.

In 2000, Buck Institute scientists made the landmark discovery that a chemical compound could extend the lifespan of simple animals. This discovery fueled speculation that human lifespan could be extended with similar antioxidant compounds. In this follow up study, the scientists chose antioxidants readily available at health food stores along with those commonly used by chemists in various skin care or food products. The four which extended lifespan (by 15% – 20%) in the nematodes are Lipoic Acid, Propyl gallate, Trolox and Taxifolin.

References

1. Lipoic Acid improves hypertriglyceridemia by stimulating triacylglycerol clearance and downregulating liver triacylglycerol secretion. Judy A. Butlera, Tory M. Hagena, b, Régis Moreaua. Archives of Biochemistry and Biophysics Volume 485, Issue 1, 1 May 2009, Pages 63–71

2. Dietary Alpha-Lipoic Acid supplementation inhibits atherosclerotic lesion development in apolipoprotein E-deficient and apolipoprotein E/low-density lipoprotein receptordeficient mice. Zhang WJ, Bird KE, McMillen TS, LeBoeuf RC, Hagen TM, Frei B. Circulation. 2008 Jan 22;117(3):421-8.