ALPHA LIPOIC ACID
Written by Slawomir (“Swavak”) Gromadzki, MPH
WHAT IS ALPHA LIPOIC ACID?
Alpha lipoic acid (ALA), also known as lipoic acid or thioctic acid, is a sulphur-containing vitamin-like antioxidant which was first isolated in 1957. It is produced naturally in human body where it has dual role; it is a key component for producing cellular energy (ATP) and a powerful antioxidant. ALA can deliver its effect to any type of cell or tissue, and at the same time it can also accumulate in the body to be used according to the needs. This universal action and benefit of this powerful enzyme is even further extended by the fact that it can function in both its forms oxidised (lipoic acid) and reduced (dihydrolipoic acid).
In some European countries ALA has been used for decades to help regulate blood glucose levels or to prevent and reduce heart damage and cataract. In Germany, for instance, ALA has been approved as a drug recommended and prescribed for the treatment of neuropathies such as peripheral neuropathy (a damaging side effect of high chemotherapy, chronic blood sugar levels or cholesterol-lowering drugs such as statins).
As an antioxidant, ALA is unique because it is both fat- and water-soluble; thus it can be used throughout human organism. ALA is also a superior anti-inflammatory agent because it is able to penetrate all parts of the cell. Inside our cells, it is broken down to dihydrolipoic acid, which is regarded as even more powerful free-radical scavenger.
Since ALA is both fat- and water-soluble, it is effective against much broader range of free radicals than other antioxidants such as vitamin C (only water soluble) or vitamin E (only fat-soluble). That is why taking ALA supplements has been proven to be an effective treatment against scurvy, in spite of the fact that scurvy is caused by vitamin C deficiency. Due to its unique and universal properties ALA can be effectively used in all regions of the human body, whereas other antioxidants, with few exceptions, can only protect isolated areas. Increased levels of ALA regenerates ascorbic acid (vitamin C) from its oxidised form (dehydroascorbic acid) thus increasing the levels of cellular vitamin C. It does exactly the same job with vitamin E.
MOST EFFECTIVE WAY TO INCREASE GLUTATHIONE
There are many reasons to assume that the most important antioxidant to overall health and longevity in our body is glutathione. Unfortunately, glutathione supplementation has not been proven to be an effective way due to poor absorption and because it has low ability to accumulate in our brain. Fortunately, ALA has been shown an excellent ability to increase intracellular glutathione levels. As a matter of fact, it is regarded as the most effective way to boost this critical antioxidant, and in one study it even managed to increase glutathione by about 70%! It does it by both regenerating glutathione from its oxidised form and by providing cysteine for the synthesis of glutathione. For instance, in a study conducted by Dr. Fuchs and colleagues, almost all participants who received 150 mg of ALA supplement three times a day for only two weeks significantly increased total glutathione levels in all seven patients. In addition, it has been discovered that ALA is also able to enhance and extend the effectiveness of other common antioxidants.
In addition, ALA increases levels of coenzyme Q10, another powerful antioxidant which is present in every cell in our body (especially in the heart) where it also plays an important role in energy production.
DETOXIFICATION AGENT & HEAVY METAL CHELATOR
ALA is regarded as one of the most effective detoxification aids as it can reduce chemical toxicity in tissues and counteract subsequent oxidative stress changes. This benefit of ALA has been shown with regards to cyanate poisoning, ifosfamide (chemotherapy drug), and toxic mushroom poisoning.
ALA works as a chelator (remover) of toxic minerals and heavy metals (such as lead or mercury) from our body. It is also able to chelate iron which tends to be catalysed into a harmful activity by the antibiotic gentamicin (combination of gentamicin and iron leads to the formation of free radicals). Unfortunately, iron sometimes works as a pro-oxidant, and therefore it can significantly increase the harmful free-radical activity. It means that Alpha lipoic acid has also the ability to disarm the harmful iron!
BLOOD GLUCOSE REGULATOR & METABOLISM BOOSTER
ALA is involved in the metabolic process of converting sugar into energy. When carbohydrates are metabolized to generate energy, they are converted to glucose and glucose into pyruvic acid (pyruvate), which is farther broken down by an enzyme complex that contains thiamine, niacin, and ALA. In this way ALA is involved in our body in the process of maintaining healthy metabolism and blood glucose levels.
ALA demonstrated its ability to stimulate sugar uptake by muscle cells in a similar way as insulin, which indicates it can be beneficial in managing hyperinsulinaemia and insulin resistance. Insulin resistance is a hazardous condition as it increases the risk of other problems such as high blood pressure, heart attack, stroke or overweight and obesity. In insulin resistance our cells do not uptake enough sugar from the blood in response to the action of normal blood insulin levels. As a result a higher levels of this hormone are required in the blood to force cells to absorb more glucose. Unfortunately, the more insulin in the blood the more weight we tend to gain and we also struggle to efficiently convert fuel into energy. Consequently, we not only store more fat but feel tired and therefore crave sugar as it is a quick source of energy. Since ALA can improve insulin sensitivity and has a positive effect on blood sugar it has been often recommended for diabetics. In one study, for instance, a daily dosage of 1200mg of ALA (600mg twice a day) for one month significantly increased insulin sensitivity and glucose uptake by body cells in both obese and lean subjects.
In addition, when there are sufficient levels of this antioxidant in our body, there is a need for increased energy expenditure, and excess calories are needed to be burned. In this way ALA helps us to boost metabolism and maintain a healthy body weight.
HEALTHY SKIN PROMOTER
By maintaining normal blood sugar levels ALA also reduces glycation process in which proteins react with excess sugar resulting in a harmful effect which is compared to oxidative damage triggered by free radicals. In this way ALA helps our body to slow down the ageing process and also offers a significant benefit in improving condition of our skin. This effect is explained by the fact that through increasing glutathione ALA actually helps prevent glycation (the free radical damage caused by sugar’s toxic effects) and collagen ‘cross-linking’. When collagen cross-links, it becomes stiff and inflexible, leading to the wrinkling and stiffness of the skin.
NERVOUS SYSTEM & BRAIN SUPPORT
All the time our bodies experience what is referred to as oxidative damage caused by free radicals. This damage takes place when our organism is unable to detoxify itself and neutralise the harmful effect of free radicals at an appropriate rate, and when it is exposed to too many harmful factors and inflammations. ALA, however, being a powerful antioxidant which is used throughout the body, is capable of reducing the damage caused by free radicals and even increase nerve regeneration rates. It can, therefore, be also of aid to nervous system injuries. Since ALA has demonstrated neuro-protective abilities and proved to be effective in improving blood flow to the peripheral nerves and stimulating regeneration of nerve fibres, it is being studied in the treatment of multiple sclerosis (MS), Parkinson’s disease or Alzheimer’s. For instance, ALA can benefit the brain by reducing amyloid-beta-induced inflammation (factor present in the onset and degeneration of Alzheimer’s disease) and increasing neurotransmitter activity within the brain via chemical signalling molecules. ALA also helps maintain glutathione levels which are found to be depleted in conditions such as Parkinson’s disease. A 2015 research paper, which analysed previous scientific data on ALA, concluded that the antioxidant showed the most consistent benefit for multiple sclerosis (MS) in preclinical studies. According to a 2016 study ALA and carnitine had a beneficial role in the prevention of MS associated with development of type 2 diabetes. Examination of current medical research reveals protective effects of ALA also in cerebral ischemia-reperfusion, mitochondrial dysfunction, inborn errors of metabolism, excitotoxic amino acid brain injury, neuropathies, and other causes of chronic or acute damage to nerve tissue including brain.
REJUVENATING & ENERGISING EFFECT
Scientists have discovered that teamwork between Alpha lipoic acid and Acetyl L-carnitine can increase energy in muscle cells allowing to lead a more active lifestyle. According to a study conducted at the University of California, Berkeley, Research Institute Alpha lipoic acid together with Acetyl L-carnitine were able to impose a huge energising and rejuvenating effect on ageing rats, and might do the same for ageing humans. A team of scientists led by Bruce N. Ames, professor of molecular and cell biology at UC Berkeley, supplemented old rats with ALA and Acetyl-L-carnitine. As a result, not only the memory of the rats was significantly improved, but they also had much more energy. According to Professor Ames, “With the two supplements together, these old rats got up and did the Macarena. The brain looked better, they were full of energy – everything we looked at looks more like a young animal!”
Also another scientist associated with the same study, Professor Tory M. Hagen, suggested that they actually observed “a reversal in loss of memory” and “a dual-track improvement which was significant and unique that is really starting to explode and move out of the realm of basic research into people. We significantly reversed the decline in overall activity typical of aged rats to what you see in a middle-aged to young adult rat. This is equivalent to making an 80-year-old individual act as middle-aged person!”
Both chemicals are normally used in mitochondria, which is regarded as the “weak link in ageing”, because deterioration of mitochondria, triggered mainly by free radicals, is an important cause of ageing, fatigue and impaired cognitive functions of the brain. The study, however, demonstrated that the two chemicals are able to “fix” the energy-producing mitochondria and greatly improve its function thus increasing the efficiency of mitochondria in empowering all cells, including brain cells. Ageing is caused by oxidizing certain proteins in mitochondria causing them to lose their activity. The supplementation with ALA and Acetyl L-carnitine, however, can reduce or even reverse the process to certain extent, because Acetyl L-carnitine at higher concentrations can even enable them to work again, while ALA does not allow radicals to damage them. It means each antioxidant solves a different problem and therefore when they are used together they produce better results than either one alone.
In another experiment the same group of scientists fed old rats a similar diet with the two supplements and looked at memory function. They found that supplementation improved both spatial and temporal memory, and reduced the amount of oxidative damage to RNA in the brain’s hippocampus, an area important in memory. In electron microscope pictures of cells from the hippocampus and mitochondria showed less structural decay in old rats that had received the two supplements.
OTHER HEALTH BENEFITS
According to the results of a study published in 2013, ALA and superoxide dismutase appeared to be beneficial in the treatment of chronic low back pain. The study found over 65% decrease in subjects requiring pain killers. The supplementation with both antioxidants also significantly reduced pain and disability among participants.
In 2008 it was shown ALA and Acetyl-L-carnitine can reduce sciatic pain caused by a herniated disc.
ALA has been shown the ability to reduce the degree of bone loss in osteoporosis in women during menopause.
In 2007 ALA together with Acetyl L-carnitine appeared to lower blood pressure and was able to improve vascular function in patients with coronary artery disease.
ALA is known to prevent Nuclear Factor kappa-B complex found in our cells from activating oncogenes that contribute to cell proliferation which increases the risk of malignant cancer. When these oncogenes are altered and activated by carcinogens or NF kappa-B, they can transform a previously benign cells into malignant cancer cells.
ALA has been demonstrated the ability to strengthen the immune system by improving antibody response in immunosuppressed animals.
A 2010 study demonstrated ALA had a therapeutic effect in lean, nondiabetic patients with polycystic ovary syndrome.
In an animal study ALA reduced ethanol self-administration in rats suggesting it might be beneficial for people who are addicted to alcohol.
Medical research suggests ALA supplements to be beneficial in other conditions including heart disease, liver cirrhosis or cataracts.
Taking into consideration all the mentioned above possible tremendous health benefits of ALA, there is no doubt it should be regarded as one of the most important dietary supplements for anyone who aims at slowing down the ageing process, increasing energy, protecting and strengthening nervous system or maintaining healthy blood glucose levels and metabolism.
Ingested in the form of a supplement ALA is converted to its reduced form of dihydrolipoic acid (DHLA) in most of the body’s tissues and used wherever it is required.
It is believed that although under normal circumstances human body can make enough ALA (from fatty acids and cysteine) to prevent recognisable deficiency symptoms, yet due to various factors the demand for this antioxidant is much higher. Unfortunately, also the fact that ALA can be naturally found in certain foods (especially spinach and brewer’s yeast) doesn’t seem to solve the problem as even these foods are still too low in ALA, and in addition, a typical refined Western diet is usually deprived of this antioxidant. A proper dietary supplementation is, therefore, the best way to prevent the deficiency, all the more since it has been suggested that ALA in the form of a 200mg-600mg supplement can provide 1000 times the amount of ALA consumed with most diets.
The optimal level of ALA varies with each person depending on the level of oxidative stress, lifestyle, diet, age, health conditions, pollution, toxins and other factors that lead to deficiency of this most vital antioxidant. It is therefore believed that an average person, especially in developed countries, is usually deficient in ALA and requires supplementation in order to meet all its metabolic and antioxidant needs.
There’s no straightforward or strict recommendation with regards to dosage as each one of us may have different needs. Usually 200 to 1800 mg per day are recommended. But there are individuals who take up to 3,000 mg of ALA per day, claiming this dose is most effective for them. Most experts suggest starting from a smaller dosage of about 200mg a day which should be slowly increased according to the needs and professional recommendations.
The best time to take ALA supplements seem to be about 30 minutes before meals as lower levels of absorption are observed when consumed with food due to a degree of competition for the carrier proteins required for absorption.
There are reasons to believe it is much better to divide ALA into at least three smaller dosages during the day instead of taking one larger.
It is also beneficial to stop taking the supplement for a week after each month and for a month or so after every 3 months, as otherwise our body may get an impression it doesn’t have to make own lipoic acid since there is a constant and sufficient supply.
With regards to supplementation it is important to choose one from a reliable source to make sure you get product of a high quality. ALA should be packed in capsules because it is an unstable molecule (easily degraded when exposed to the atmosphere and light), and therefore any ALA in a powdered form can be questionable.
SAFETY & CONTRAINDICATIONS
Alpha lipoic acid supplementation is regarded as very safe. During decades of testing and extensive use in numerous clinical trials in the treatment of various neuropathies, there have been no reports describing side effects caused by normal doses of this antioxidant. Large scale human studies demonstrated that taking up to 2400mg per day caused no adverse effects even when used for over 6 months.
The dosage should be based on professional recommendations, the needs, health conditions, reaction and experience of each person following ingestion.
As a precaution, and until sufficient data is available, ALA is generally not recommended for pregnant women.
In addition, according to some experts such as Dr. Packer, ALA may compete with Biotin and interfere with its activity in human organism. For this reason, Biotin supplementation is recommended if the daily intake of ALA exceeds 200mg.
Rochette L, Ghibu S, Richard C, et al. (2013) Direct and indirect antioxidant properties of α-lipoic acid and therapeutic potential. Molecular Nutrition & Food Research 57:114-125. PMID
Goraca A, Huk-Kolega H, Piechota A, et al. (2011) Lipoic acid—biological activity and therapeutic potential. Pharmacological Reports 63:849-858. PMID: 22001972
Berkson, B. 1998, The Alpha Lipoic Acid Breakthrough. Rockilin, CA: Prima Publishing.
Packer L, Tritschler H, Wessel K (1997) Neuroprotection by the metabolic antioxidant alpha-lipoic acid. Free Radical Biology & Medicine 22:359-378. PMID: 8958163
Fuchs, J. et al. (1993) Studies on lipoate effects on blood redox state in human immunodeficiency virus (HIV 1) replication. Arzeim Forsch 43, 1359-1362,1993.
Han D, Tritschler H, Packer L (1995) Alpha-lipoic acid increases intracellular glutathione in a human T-lyphocyte Jurkat cell line. Biochemical and Biophysical Research Communications 207:258-264. PMID: 7857274
Golan, R.1995. Optimal Wellness. New York: Ballentine books.
Jacob, S. et al., Enhancement of Glucose Disposal in Patients with Type 2 diabetes by Alpha Lipoic Acid. Arzeim Forsch 45,872-874,1995.
Klip, A. et al.,Glucose Transporters of Muscle Cells in Culture. Molecular Biology of Diabetes. N.J.: Humana Press, 1994.
Murray, M. 1996. Encyclopedia of Nutritional Supplements. Rocklin, Ca: Prima Publishing.
Murray, M. & Pizzorno, J. 1998, Encyclopedia of Natural Medicine. Rocklin, CA: Prima Publishing.
Packer, L. (1994) Antioxidant Properties of Lipoic Acid and its Therapeutic Effects in Prevention of Diabetes Complications and Cataracts. Annals NY Acad Sci 738, 257-264, 1994.
Packer, L.& Tritschler, H. (1995) Alpha Lipoic as a Biological Antioxidant. Free Rad Biol Med 19, 227-250, 1995.
Passwater, R. 1995. Lipoic Acid: The Metabolic Antioxidant.New Canaan, Conneticut: Keats Publishing.
Quillin, P. & N. 1998. Beating Cancer with Nutrition. Tulsa, OK.: Nutrtion Times Press.
Quillin, P. & Reynolds, A. 1988. The La Costa Book of Nutrition. New york: Pharos Books.
Quillin, P. 1989. Healing Nutrients. New York: Random House.
Scott, B. et al., (1994) Lipoic and Dihydrolipoic Acids as Antioxidants: A Critical Review. Free Rad Res 20, 119-133, 1994.
Somer, E. 1995. The Essential Guide to Vitamins and Minerals. New York: Harper Collins.
Wagh, S. et al. (1987) Mode of Action of Lipoic Acid in Diabetes. Journal of Bioscience. 11:59-75 (1987).
McCarty M, Barroso-Aranda J, Contreras F (2009) The “rejuvenatory” impact of lipoic acid on mitochondrial function in aging rats may reflect induction and activation of PPAR-gamma coactivator-1alpha. Medical Hypotheses 72:29-33. PMID: 18789599
Dietary supplements make old rats youthful, may help rejuvenate aging humans, according to UC Berkeley study. 19 February 2002: http://www.berkeley.edu/news/media/releases/2002/02/19_diet.html
Masharani U, Gjerde C, Evans JL, Youngren JF, Goldfine ID (2010) Effects of controlled-release alpha lipoic acid in lean, nondiabetic patients with polycystic ovary syndrome. J Diabetes Sci Technol. 2010 Mar 1;4(2):359-64.
Antonio Memeo, Mario Loiero (2008) Thioctic acid and acetyl-L-carnitine in the treatment of sciatic pain caused by a herniated disc: a randomized, double-blind, comparative study. Clin Drug Investig. 2008; 28(8):495-500. PMID: 18598095
Hala M Abdelkarem, Laila H Fadda, Abeer A G Hassan (2016) Potential Intervention ofα- Lipoic Acid and Carnitine on Insulin Sensitivity and Anti-Inflammatory Cytokines Levels in Fructose-Fed Rats, a Model of Metabolic Syndrome. J Diet Suppl. 2016 Aug 5:1-11. Epub 2016 Aug 5. PMID: 27494173
Konrad T, Vicini P, Kusterer K, et al. Alpha-lipoic acid treatment decreases serum lactate and pyruvate concentrations and improves glucose effectiveness in lean and obese patients with type 2 diabetes. Diabetes Care 1999;22:280-287.
Plemel JR, Juzwik CA, Benson CA, Monks M, Harris C, Ploughman M. (2015) Over-the-counter anti-oxidant therapies for use in multiple sclerosis: A systematic review. Mult Scler. 2015 Oct;21(12):1485-95. doi: 10.1177/1352458515601513. Epub 2015 Aug 18.
Singh U, Jialal I (2008) Alpha-lipoic acid supplementation and diabetes. Nutrition Reviews66:646-657. PMID: 19019027
Ranieri M, Sciuscio M, Cortese AM, Santamato A, Di Teo L, Ianieri G, Bellomo RG, Stasi M, Megna M. (2009) The use of alpha-lipoic acid (ALA), gamma linolenic acid (GLA) and rehabilitation in the treatment of back pain: effect on health-related quality of life. Int J Immunopathol Pharmacol. 2009 Jul-Sep;22(3 Suppl): 45-50.
Priuska EM, Schacht J. (1995) Formation of free radicals by gentamicin and iron and evidence for an iron/gentamicin complex. Biochem Pharmacol. 1995 Nov 27;50(11):1749-52.
Battisti E, Albanese A, Guerra L, et al. (2013) Alpha lipoic acid and superoxide dismutase in the treatment of chronic low back pain. European Journal of Physical and Rehabilitation Medicine Jul 9 [Epub ahead of print] PMID: 23860422
Li R, Ji W, Pang J, et al. (2013) Alpha-lipoic acid ameliorates oxidative stress by increasing aldehyde dehydrogenase-2 activity in patients with acute coronary syndrome. The Tohoku Journal of Experimental Medicine 229:45-51. PMID: 23238616
Kleinkauf-Rocha J, Bobermin L, Machado M, et al. (2013) Lipoic acid increases glutamate uptake, glutamine synthetase activity and glutathione content in C6 astrocyte cell line. International Journal of Developmental Neuroscience 31:165-170. PMID: 23286972
Peana A, Muggironi G, Fois G, Diana M (2013) Alpha-lipoic acid reduces ethanol self-administration in rats. Alchoholism, Clinical and Experimental Research Jun 26 [Epub ahead of print] PMID: 23802909
Sokolowska M, Lorenc-Koci E, Bilska A, Iciek M (2013) The effect of lipoic acid on cyanate toxicity in different structures of the rat brain. Neurotoxicity Research 24:345-357. PMID: 23625581
Singh U, Jialal I (2008) Alpha-lipoic acid supplementation and diabetes. Nutrition Reviews66:646-657. PMID: 19019027
Patrick L (2002) Mercury toxicity and antioxidants: part I: role of glutathione and alpha-lipoic acid in the treatment of mercury toxicity. Alternative Medicine Review 7:456-471. PMID: 12495372
Kapoor S (2013) The anti-neoplastic effects of alpha-lipoic acid: clinical benefits in system tumors besides lung carcinomas. The Korean Journal of Thoracic and Cardiovascular Surgery 46:162-163. PMID: 23614108
Michikoshi H, Nakamura T, Sakai K, et al. (2013) α-Lipoic acid-induced inhibition of proliferation and met phosphorylation in human nonsmall cell lung cancer cells. Cancer Letters 335:472-478. PMID: 23507559