Occurrence and importance

Structure of α-lipoic acid

α-Lipoic acid (engl. alpha linoic acid, ALA for short), also known as thioctic acid, is a short-chain fatty acid which, according to studies, has a promising potential to counteract the development and progression of dementias such as Alzheimer’s disease. The fatty acid can be produced by the human body itself, but can also be absorbed from animal and plant foods. Particularly good sources are meat and organs such as the heart, liver and kidneys, which are rich in mitochondria. ALA is also found in fruit and vegetables, with different types of cabbage in particular being a rich source.

With ALA, a distinction is made between R-α-lipoic acid and S-α-lipoic acid. R-α-lipoic acid occurs naturally in plants, animals and humans, while S-α-lipoic acid is produced synthetically. It is important to note that R-α-lipoic acid is better recognized and metabolized by the body than S-α-lipoic acid. For this reason, R-α-lipoic acid is considered to be the more biologically active form [8].

α-Lipoic acid and its effects in the brain

Antioxidant effect

As an antioxidant, ALA can scavenge free oxygen radicals (ROS), which are formed to an above-average extent in Alzheimer’s patients in particular. Too many ROS lead to a condition known as oxidative stress, i.e. an imbalance between ROS and antioxidant forces in the body. Among other things, ROS damage nerve cells, lead to their premature death and can thus contribute to the development of Alzheimer’s disease. Unlike other antioxidants, ALA is both water- and fat-soluble due to its chemical structure. ALA can therefore cross cell membranes as well as the blood-brain barrier.

As the most powerful natural antioxidant, ALA also has the ability to chemically reduce other antioxidants, such as glutathione, coenzyme Q10, vitamin C and E, and thus recycle them into their biologically active form. ALA therefore increases the cellular availability and functionality of these substances without having to substitute them [10].

Glutathione in particular is the most important antioxidant in the brain when it is present in its reduced form. If (reduced) glutathione scavenges ROS in the brain, this can reduce plaque formation and improve the memory performance of Alzheimer’s patients. However, glutathione itself is oxidized and consumed in the process and must therefore be restored to its biologically active form. According to study data, increased consumption of intracellular glutathione can be fully or partially compensated for by the administration of ALA [10]. ALA can also bind redox-active metals such as copper, iron or zinc. These promote ROS formation and plaque formation between the nerve cells [1, 7].

Neurotransmitter synthesis

Neurotransmitters such as acetylcholine (ACh) are messenger substances that transmit signals between nerve cells. ACh is formed from choline and acetyl-CoA, the end product of glycolysis (energy production from sugar). A lack of acetylcholine has been observed in Alzheimer’s patients, which can be triggered by a disturbance in sugar metabolism. In addition, the enzyme acetylcholinesterase breaks down acetylcholine at an above-average rate in Alzheimer’s patients. ALA can influence the activity of this enzyme and thus counteract the breakdown of acetylcholine and help to maintain memory performance [1, 7].

Energy metabolism

ALA is also an important co-factor in many enzymes of the energy metabolism. For example, the fatty acid can increase the formation of glucose transporters in the brain, which increases glucose uptake into the neuronal cells. This counteracts a glucose deficiency in the brain, which is also a cause of the onset and development of Alzheimer’s disease. At the same time, ALA has an important function in energy production in the mitochondria. It acts as an electron acceptor in enzyme complexes of the respiratory chain in the mitochondrial membrane and protects it from oxidative stress [1, 7].

Detoxification

ALA can also support the excretion of foreign substances. In particular, it can dissolve metal ions such as lead, mercury, copper, iron and platinum from their binding to sulphur-containing proteins in the tissue and excrete them via the bile. Due to its fat solubility, ALA also reaches intracellular compartments and penetrates the blood-brain barrier, which is of particular importance in the prevention of Alzheimer’s disease [2].

The effect of α-lipoic acid on Alzheimer’s patients

The effectiveness of ALA in Alzheimer’s patients has already been demonstrated in numerous studies [4]. Cognitive abilities are assessed in these studies using the Mini-Mental Status Examination (MMSE) or the Alzheimer’s Disease Cognitive Subscale (ADAScog). These cognitive tests include spatial and temporal orientation, language comprehension and use, calculation skills and basic motor skills. Based on the score achieved, the extent of cognitive impairment can be assessed from severe (≤9 points) to moderate (10-18 points) to mild (19-23 points). In addition, certain biomarkers in the body can be examined in order to investigate the effect of ALA.

  • In one study, patients were divided into three groups: Group 1 with mild dementia, Group 2 with moderate dementia in the early stages and Group 3 with moderate dementia in the advanced stages. Over a period of 48 months, all three groups received 600 mg of ALA daily as well as acetylcholinesterase inhibitors and cognitive training. Compared to other studies, patients who also took ALA showed a slower progression of the disease. Particularly in patients with mild and moderate dementia in the early stages, the course of the disease slowed significantly and after three years the progression of the disease was comparatively slower [6].
  • Similar results were obtained in a study by Hager et al. achieved. In this study, 9 Alzheimer’s patients received 600 mg ALA daily for 12 months. With the help of the MMSE and ADAScog, it was shown that cognitive functions stabilized after the intervention. This analysis was extended 6 years later with 43 patients over an observation period of 48 months. The progression of Alzheimer’s disease was slower in patients who supplemented with ALA than in untreated patients [5].
  • In the study by Shinto et al. 39 Alzheimer’s patients were divided into three groups. Group 1 received a placebo, while group 2 received omega-3 fatty acids (ω-3), which also show a therapeutic effect on Alzheimer’s disease. Group 3 received a combination of ω-3 and ALA . Compared to the placebo group, patients who supplemented with ω-3+ALA achieved reduced cognitive decline and an improved ability to carry out everyday activities independently [11].
  • In another study by Galasko et al. 78 Alzheimer’s patients were divided into three groups. Group 1 received a combination of vitamin E (800 IU), vitamin C (500 mg) and ALA (900 mg) per day. Group 2 received coenzyme Q (1200 mg) daily and group 3 a placebo. Group 1 had reduced biomarkers of oxidative stress after the intervention, which in turn indicates reduced oxidative stress in the brain. In addition, group 1 showed less cognitive decline compared to the placebo group [4].
  • However, in an open-label pilot study in cognitively intact older adults, no significant effects of ALA (600 mg/day) on cognition or mood were observed after 12 weeks. This suggests that the benefits of ALA may be more pronounced in people with existing cognitive impairment [1]

These studies show that supplementation with ALA can slow down cognitive decline in Alzheimer’s patients and preserve their ability to perform everyday activities. A combination with other antioxidants such as vitamin E or omega-3 fatty acids can also be beneficial. Studies suggest that a dosage of 600-1200 mg ALA per day is suitable for Alzheimer’s patients. However, this dose cannot be covered by a diet rich in ALA, but must also be supplemented with food supplements.

It is important to mention that ALA cannot cure dementia. However, as the intervention studies show, it can be used preventively or therapeutically to counteract the progression of the disease.

If you want to find out more about other beneficial fatty acids or which fats you should avoid if you have dementia, click here. To find out more about ALA and other therapeutic uses, click here.

References

  1. Basile, G. A., Iannuzzo, F., Xerra, F., Genovese, G., Pandolfo, G., Cedro, C., Muscatello, M. R. A., & Bruno, A. (2023). Cognitive and Mood Effect of Alpha-Lipoic Acid Supplementation in a Nonclinical Elder Sample: An Open-Label Pilot Study. International Journal of Environmental Research and Public Health, 20 (3), 2358. https://doi.org/10.3390/ijerph20032358
  2. Ciftci, H., & Bakal, U. (2009). The Effect of Lipoic Acid on Macro and Trace Metal Levels in Living Tissues Exposed to Oxidative Stress. Anti-Cancer Agents in Medicinal Chemistry, 9 (5), 560-568. https://pubmed.ncbi.nlm.nih.gov/19519297/
  3. De Sousa, C. N. S., da Silva Leite, C. M. G., da Silva Medeiros, I., Vasconcelos, L. C., Cabral, L. M., Patrocínio, C. F. V., Patrocínio, M. L. V., Mouaffak, F., Kebir, O., Macedo, D., Patrocínio, M. C. A., & Vasconcelos, S. M. M. (2019). Alpha-lipoic acid in the treatment of psychiatric and neurological disorders: A systematic review. Metabolic Brain Disease, 34 (1), 39-52. https://doi.org/10.1007/s11011-018-0344-x
  4. Galasko, D. R., Peskind, E., Clark, C. M., Quinn, J. F., Ringman, J. M., Jicha, G. A., Cotman, C., Cottrell, B., Montine, T. J., Thomas, R. G., Aisen, P., & Alzheimer’s Disease Cooperative Study, for the. (2012). Antioxidants for Alzheimer Disease: A Randomized Clinical Trial With Cerebrospinal Fluid Biomarker Measures. Archives of Neurology, 69 (7), 836-841. https://doi.org/10.1001/archneurol.2012.85
  5. Hager, K., Kenklies, M., McAfoose, J., Engel, J., & Münch, G. (2007). Alpha-lipoic acid as a new treatment option for Alzheimer’s disease-A 48 months follow-up analysis. Journal of Neural Transmission. Supplement, 72, 189-193. https://doi.org/10.1007/978-3-211-73574-9_24
  6. Hager, K., Marahrens, A., Kenklies, M., Riederer, P., & Münch, G. (2001). Alpha-lipoic acid as a new treatment option for Azheimer type dementia. Archives of Gerontology and Geriatrics, 32(3), 275-282. https://doi.org/10.1016/S0167-4943(01)00104-2
  7. Kaur, D., Behl, T., Sehgal, A., Singh, S., Sharma, N., Chigurupati, S., Alhowail, A., Abdeen, A., Ibrahim, S. F., Vargas-De-La-Cruz, C., Sachdeva, M., Bhatia, S., Al-Harrasi, A., & Bungau, S. (2021). Decrypting the potential role of α-lipoic acid in Alzheimer’s disease. Life Sciences, 284 , 119899. https://doi.org/10.1016/j.lfs.2021.119899
  8. Liu, Q., Li, W., Huang, S., Zhao, L., Zhang, J., Ji, C., & Ma, Q. (2022). R- Is Superior to S-Form of α -Lipoic Acid in Anti-Inflammatory and Antioxidant Effects in Laying Hens. Antioxidants, 11 (8), Article 8. https://doi.org/10.3390/antiox11081530
  9. Patrick, L. (2002). Mercury toxicity and antioxidants: Part 1: role of glutathione and alpha-lipoic acid in the treatment of mercury toxicity. Alternative Medicine Review: A Journal of Clinical Therapeutic, 7 (6), 456-471. https://pubmed.ncbi.nlm.nih.gov/12495372/
  10. Salehi, B., Berkay Yılmaz, Y., Antika, G., Boyunegmez Tumer, T., Fawzi Mahomoodally, M., Lobine, D., Akram, M., Riaz, M., Capanoglu, E., Sharopov, F., Martins, N., Cho, W. C., & Sharifi-Rad, J. (2019). Insights on the Use of α-Lipoic Acid for Therapeutic Purposes. Biomolecules, 9 (8), Article 8. https://doi.org/10.3390/biom9080356
  11. Shinto, L., Quinn, J., Montine, T., Dodge, H. H., Woodward, W., Baldauf-Wagner, S., Waichunas, D., Bumgarner, L., Bourdette, D., Silbert, L., & Kaye, J. (2014). A Randomized Placebo-Controlled Pilot Trial of Omega-3 Fatty Acids and Alpha Lipoic Acid in Alzheimer’s Disease. Journal of Alzheimer’s : JAD, 38 (1), 10.3233/JAD-130722. https://doi.org/10.3233/JAD-130722

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