Alpha Lipoic Acid (ALA) is an antioxidant which has been used for stabilizing blood sugar levels, reducing inflammation, promoting cardiovascular health, improving nerve function, and to slow general aging.
A Powerful Antioxidant
Antioxidants are substances that attack “free radicals”. Free radicals in the body play a part in biochemical reactions that damage cells and body tissues. As such they damage our organs, reducing their
functioning. Some antioxidants are either water soluble (such as vitamin C) or fat soluble (such as vitamin E). Alpha-lipoic acid is both fat- and water- soluble, which means that it can work throughout the body. ALA or its reduced form (dihydrolipoic acid) quenches several oxygen-free radical species in both aqueous and lipid phases (Sacks et al. 2018). As antioxidants become depleted in the body as they are used up in their fight against free radicals, alpha-lipoic acid can help to regenerate other antioxidants, making them active again. One example of this is its ability to recycle glutathione – one of the body’s essential antioxidants in its fight against free radicals.
ALA has been extensively studied since the 1950’s, when its antioxidant properties were first discovered [100]. It has been demonstrated that ALA is effective in relieving some of the symptoms or complications related to certain diseases, such as diabetes, age-related cardiovascular and neuromuscular defects, and metabolic obesity [29,89,101,102]. Its potential effects on different types of diseases have drawn attention especially in the field of neurodegenerative conditions [103].
ALA has been recommended for:
- Chronic Fatigue Syndrome (CFS)
- Peripheral Artery Disease (PAD)
- Diabetes
- Dementia
- Liver Disease
- Cardiac Autonomic dysfunction
- Degenerative Neurological Diseases
- Neuropathy
- Cataracts
- Kidney Disease
- Cardiovascular Disease
- Intermittent Claudication
- https://pmc.ncbi.nlm.nih.gov/articles/PMC2756298/
https://drsobo.com/lipoic-acid-ivs/
The Effects of α-Lipoic Acid on Diabetic Patients with Neuropathy
The complications of diabetes fall into two categories: macrovascular and microvascular complications. Retinopathy, nephropathy, and neuropathy are well-characterized microvascular complications, and the development of neuropathy is closely related to the severity and duration of hyperglycemia [105]. Diabetic neuropathy has also been recognized as a major cause of both morbidity and mortality [106].
Beneficial effects of ALA on diabetes-associated neuropathy have been demonstrated by numerous clinical trials . In a randomized, double-blind, placebo-controlled, multicenter study by Ziegler et al. [107], ALA was shown to be effective against mild-to-moderate diabetic sensorimotor polyneuropathy (DSPN). The treatment of diabetic patients with mild-to-moderate DSPN were given 600 mg of ALA orally per day, measurably improved the condition. This trial showed that ALA might have the potential to prevent neuropathic impairments and slow progression with regular long-term administration.
https://pmc.ncbi.nlm.nih.gov/articles/PMC9904877/
ALA’s Neuroprotective Effect
Free radical induced damage plays a role in secondary neuronal brain injury in stroke (Dwivedi 2019).The antioxidant properties of α-lipoic acid are associated with its neurorestorative and neuroprotective effects. It has been shown that intraveon α-Lipoic acid administration provides neuroprotection by increasing neurogenesis and brain cell metabolism (Choi et al. 2013). ALA modulates the expression of the pro-inflammatory cytokines IL-6, IL-1, IL-10, and tumor necrosis factor (TNF).
Neurodegeneration
Several studies have found that combining α-lipoic acid and omega-3 fatty acids has a synergistic effect in slowing functional and cognitive decline in Alzheimer’s disease (Shinto et al. 2014).
In Parkinson’s disease oxidative stress is responsible for the degeneration of dopaminergic neurons in Parkinson’s disease. ALA acid may prove useful here, and in other neurodegenerative diseases like Huntington’s disease and ataxia telangiectasia (Andreassen et al. 2001).[103].
Cardiovascular Disease
Oxidative stress and inflammation promoting activities give rise to hydroxyl radicals, peroxides, and superoxides inside the endothelium (the inner lining of blood vessels), which accelerates the progression of cardiovascular disease. Alpha lipoic acid has blood lipid modulating characteristics, protecting against LDL oxidation (and plaque formation), and modulation hypertension. Thus, administering α-lipoic acid as a protective agent might retard the development of cardiovascular disease. (Wollin and Jones 2003). The incidence of cardiovascular diseases decreases as the dietary intake of α-lipoic acid increases.
Kidney-Related Disease
In worsening chronic kidney disease, cellular metabolic changes occur leading to the production of free radicals that further the development of renal damage. The generation of lipid hydroperoxide results in oxidative damage in lipoproteins, cell membranes, and other lipid-containing structures (Girotti and Kriska 2004). a number of studies have shown that administration of α-lipoic acid (600 mg/day) with antioxidants such as α-tocopherol (Vitamin E) 300–1000 mg/day, and N-acetylcysteine (600–1200 mg/day) can help dialysis patients with elevated oxidative stress (Lim et al. 1999; Nazrul et al. 2000; Roob et al. 2000; Leehey et al. 2005).
The antioxidant activities of α-lipoic acid were shown to be more effective than N-acetylcysteine at curing oxidative stress, including diabetic neuropathy and glomerular injury. ALA administration lead may lead to a reduction in measurable oxidative stress markers. In one study, patients with autosomal dominant polycystic kidney disease treated with α-lipoic acid had a significant improvement in metabolic and endothelial functions (Lai et al. 2020).
Inflammatory Disease
Alpha-lipoic acid is synthesized inside the human body to work as an antioxidant, safeguarding body cells from injury, and helping restore other antioxidants, like vitamins C and E (Moura et al.) 2021. It can also act as a chemopreventive agent because it inhibits inflammation which is linked to carcinogenesis (Moon 2016). Administration of α-Lipoic acid may reduce the inflammatory markers of heart disease, where oxidative stress is thought to be a significant factor. Oxidative stress increases during the aging process, resulting in either enhanced Reactive Oxygen Species (ROS) and diminished antioxidant safeguards. Aging is also related to oxidative stress, which in turn leads to hastened cellular senescence and organ dysfunction. Antioxidants may assist in reducing the incidence of some of the pathologies of heart disease (Wollin and Jones 2003). It has been found that α-lipoic acid can protect the liver from inflammatory disorders as well. In this context ALA may help reduce the blood levels of several inflammatory markers, such as IL-6 (Liu et al. 2015). No side effects seem to occur after long term supplementation. (Liu et al. 2015).
Infertility
Sperm function may be negatively impacted by free radicals (Thuwanut et al. 2010). Excessive generation of ROS may promote defective spermatozoa production and contribute to infertility (Gharagozloo and Aitken 2011). Male infertility has been associated with a lower intake of antioxidant nutrients, such as carnitine, selenium, folate and vitamins A, C, and E, (Buhling and Laakmann 2014).This suggests that α-lipoic acid could improve the sperm motility rate, reduce sperm DNA damage, and thereby improve sperm quality (Ibrahim et al. 2008). Also, ALA may have a positive effect on oocyte maturation, embryo development, and reproductive outcomes (Dong et al. 2019; di Tucci et al. 2021). Regular administration of α-lipoic acid has helped to reduce the pelvic pain in those with endometriosis and normalize menstrual blood flow. Therefore, ALA represents a promising new molecule for infertility More clinical study has to be done to confirm this.
More Clinical Trials with Alpha Lipoic Acid
https://pmc.ncbi.nlm.nih.gov/articles/PMC6723188/
Effects of ALA in Overweight/Obese Patients
Obesity is a complex disorder, consisting in abnormal fat storage that may lead to serious disease. Dysfunctional adipose tissue is a major factor in obesity as well as other secondary chronic diseases as a result of insulin resistance, chronic inflammation and altered adipokines secretion [112]. The effects of ALA on weight control have been investigated by clinical trials, which have shown promising results.
In the study of Huerta et al. [114], 77 healthy overweight/obese women with BMI values between 27.5 and 40 were studied. All participants were randomly divided into 4 groups, treated with 1300 mg eicosapentaenoic acid (EPA) or 300 mg of ALA or 1300 mg of EPA plus 300 mg of ALA or placebo daily for 10 weeks. All individuals were given a 30% energy-restricted diet. The results were that the ALA treated group showed significantly higher body weight loss and an important drop in leptin levels from the first week of treatment onward. No unfavorable effects occurred.
Effects of α-Lipoic Acid in Patients with Multiple Sclerosis
Multiple sclerosis is a disabling degenerative disorder of the central nervous system (CNS) attributable to inflammation which leads to demyelination of CNS [124]. Inflammation in MS is developed by the invasion of T cells into the CNS, then they produce metalloproteinase-9 (MMP-9), which has been found to be correlated with MS relapse. Some studies proposed that ALA may be a useful drug for MS [125,126].
MS with changing periods of the appearance of further neurological damage and then recovery periods is described as a relapsing-remitting MS (RRMS), which is the most familiar type of MS. The attention on improving therapeutic agents to restrain the progressive phases of MS is expanding in recent years [127]. The effects of ALA in this aspect were also investigated through a few number of clinical trials, as shown in Table 4. In the study performed by Khalili et al. [128] the anti-inflammatory effects of daily ALA consumption on RRMS patients were investigated. Forty-six patients were separated into an ALA group, receiving 1200 mg ALA or the placebo group, which received a placebo for 12 weeks. A significant decrease in INF-γ, TGF-β, ICAM-1, and IL-4 levels was observed in the ALA group but not in the placebo group.
