HOME > Doctor’s Health Advice > Alpha lipoic acid is crucial for boosting glutathione production, particularly for the elderly

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  • Yuzo Endo, M.D., Ph.D.
  • Masahito Hitosugi, M.D., Ph.D.
  • John E. Lewis, Ph.D.

Doctor’s Health Advice

Doctor’s Health Advice

Food, Nutrition, and Exercise for Healthy Living


Alpha lipoic acid is crucial for boosting glutathione production, particularly for the elderly

As we have discussed previously in this series of articles, inflammation and oxidative stress are two significant factors that contribute to accelerated aging. To counteract these effects, we need to ensure that we have sufficiently high levels of antioxidants in our diet to stave off aging-associated complications.  In addition, when we are growing as a child and adolescent and even through young adulthood, many physiological processes are at peak capacity, such as the body’s ability to synthesize antioxidants from our food or dietary supplements to counteract oxidative stress, inflammation, and other complications.  Another important physiological function occurs metabolically through the function of enzymes.  Enzymes, through enzymatic pathways, are necessary for every biochemical reaction in our cells to sustain our lives. As we age, we slowly lose the capacity to perform these functions, particularly if we do not eat well, exercise, and engage in other health-protecting behaviors.  Gene transcription is also important to our survival, as our genes daily carry out the biochemical activities of life.  We want to provide our genes with the best information, i.e., proper nutrition, so that our genetic expression is one of health, not disease.  Thus, we need to know what nutrients are important for counteracting these ill effects of aging and prevent the diseases and disorders commonly associated with aging.

Within the context of preventing oxidative stress and inflammation and ensuring enzymatic and genetic pathways are functioning properly, alpha lipoic acid is a molecule intimately involved in these activities and others. Alpha lipoic acid continues to gain popularity in both the scientific community and the dietary supplement industry due to the discoveries being made that show its effects on many different genetic, enzymatic, and cellular functions.  For example, alpha lipoic acid is considered to be a potent antioxidant by its action on reactive oxygen species, which are free radicals produced through common cellular aerobic respiration or metabolism.  Reactive oxygen species have a significant impact on our endothelium, the lining of our vascular system, which is a significant risk factor for eventual cardiovascular disease, particularly as we age.  Thus, alpha lipoic acid’s ultimate effect on the prevention of cardiovascular disease should be considered.  It is also known that alpha lipoic acid is readily absorbed, quickly metabolized, and does not tend to accumulate significantly in tissue.  Thus, could its effects be more than just acting as a quick-hitting antioxidant without influencing other molecules or metabolic pathways?  Fortunately, the answer to that question appears to be “yes!”  Alpha lipoic acid is able to do much more than just scavenge free radicals in the short-term, as it has the capability to influence the overall genetic and cellular environments for the long-term, given its other effects on metabolic pathways and gene transcription.

Glutathione is considered by many to be the “master antioxidant” for the body’s defense mechanisms against oxidative stress and other insults. Several lines of research suggest that alpha lipoic acid is intimately involved in increasing the total amount and capacity of glutathione through its enzymatic actions.  Alpha lipoic acid acts on the genetic level as what is known as an inducer, meaning that it works to transcribe a gene, to enable synthesis of glutathione and ultimately to impact the amount of glutathione that is available at the cellular level.  As the inducer, alpha lipoic acid works in conjunction with Nrf2, which is important for regulating antioxidant and detoxification genes.  Alpha lipoic acid has been shown to increase the level of hepatic (liver) Nrf2.  Another recent study showed that alpha lipoic acid also had an effect on Nrf2 through the SIRT1 pathway to reduce the amount of fat and triglycerides in the liver.  Thus, alpha lipoic acid appears to have a significant impact on the synthesis of glutathione through this important gene transcription process.  Alpha lipoic acid also functions as a mediating factor to create more cysteine, which is an amino acid that is crucial for the synthesis of glutathione.  Evidence suggests that this cysteine effect may be occurring through the Nrf2 pathway as well.

Another important key molecule that is involved in various oxidative stress and inflammatory pathways is NF-κB, which is an inducer of genes that are responsible for such insults. It is now known that alpha lipoic acid inhibits the production of NF-κB, and it also decreases the ability of TNF-α to produce NF-κB as well.  TNF-α is a widely studied protein called a cytokine that is well-known for its role within the immune system and how it affects inflammation.  Thus, alpha lipoic acid may play a huge role in helping to prevent pathological levels of inflammation through its direct and indirect inhibition of NF-κB.

Although clinical trials in humans testing the effect of alpha lipoic acid are limited, it has been tested in several studies for diabetic neuropathy. Neuropathy is one of the leading complications of diabetes, not only from the perspective of pain and suffering from the individual, but also due to the financial cost to the patient and society.  Currently, conventional medical treatments for neuropathy are very limited and not very effective.  Alpha lipoic acid has been found to improve several outcomes related to diabetic neuropathy, including pain, burning, tingling, and lack of sensation.  In addition to alpha lipoic acid’s ability to influence these outcomes, it improves glucose metabolism as well.  Thus, it should likely be considered as a key tool for any person battling diabetes.

In summary, alpha lipoic acid is an important known regulatory molecule involved in many metabolic processes at the genetic, enzymatic, and cellular levels. It functions both directly and indirectly on other markers of oxidative and inflammatory status.  Unfortunately, it declines with age, which may predispose us to these aforementioned complications that could lead to cardiovascular disease, among others, through endothelial dysfunction and dysregulated immune and redox systems.  Fortunately, it has been shown in older animals that supplementing their diet with alpha lipoic acid reversed the age-related decline of glutathione, which improves the overall antioxidant status of the host.  Thus, taking a high-quality alpha lipoic acid dietary supplement is recommended as we age to counteract the natural decline associated with the aging process.  Preventing senescence in the pathways where alpha lipoic acid exerts its effects is crucial for reducing the risk of common diseases of aging.  Because alpha lipoic acid does not readily accumulate in the tissues, it is important to make it part of the daily regimen.  Lipoic acid is also typically low in foods and what is present is not readily absorbable, so being so lacking in the diet makes taking it in a supplemental form even more important.  Alpha lipoic acid is generally considered to be safe and tolerable for long-term use without any significant side effects up to 1,200 mg/day.  Consider taking 200-300 mg/day for most uses in a product that has been formulated with enhanced technology, such as a micelle or liposome, to enable your body to absorb more of it.


John E. Lewis, Ph.D.

John E. Lewis, Ph.D.
Associate Professor, University of Miami

Associate Professor of Psychiatry and Behavioral Sciences at the University of Miami Miller School of Medicine
Director of Research for the Center for Complementary and Integrative Medicine at the University of Miami Miller School of Medicine
Advisor, Diplomat, and Faculty member of the Medical Wellness Association

1990 B.S., Business Administration, University of Tennessee
1992 M.S., Exercise Physiology, University of Tennessee
1995 Ph.D., Education and Psychological Studies, University of Miami

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