Alpha Lipoic Acid

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Alpha Lipoic Acid

Alpha lipoic acid (ALA) is a sulfur-containing fatty acid compound that is naturally produced by plants and animals. In humans, it is synthesized in the mitochondria, where it functions as an essential cofactor for enzymes that participate in mitochondrial energy metabolism. However, when ALA is ingested from dietary sources, instead of functioning as an enzyme cofactor it appears to have a broader range of effects and a therapeutic potential for treating conditions such as neurodegenerative, auto-immune, and cardiovascular issues as well as liver regeneration and CFCs.

In a cell, ALA is reduced to dihydrolipoic acid (DHLA), which acts as a potent antioxidant and therefore modulates oxidative stress and inflammatory pathways. Studies done with ALA have revealed several effects that can be used to eliminate CFCs by targeting metabolic pathways essential and specific for them and to support healthy body functions of the person treated. Some of the benefits of ALA are:

Supporting Antioxidative and Detoxification Processes

ALA has been found to reduce oxidative stress by restoring levels of antioxidants such as vitamin C and glutathione and chelating metals and removing them from blood. ALA also enhances the production of phase II detoxifying enzymes such as glutathione S-transferases and NAD(P)H: quinone oxidoreductase which are specialized for neutralizing a variety of carcinogenic compounds that can eventually lead to the development of CFCs. ALA induces synthesis of the enzymes by activating a transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2). Nrf2 binds to the antioxidant response element (ARE) which in turn activates the expression of genes for phase II enzymes. Experimental studies on mice have demonstrated the necessity of these enzymes in preventing the formation of CFCs since mice lacking Nfr2 activity are unable to produce these enzymes in response to carcinogens and consequently develop CFCs significantly more often. 

ALA can prevent the formation and accumulation of advanced glycation (adding sugar) end products (AGEs). AGEs are formed in protein glycation, also known as the Maillard reaction, which is a complex chemical reaction between reducing sugars and amino acids of proteins. This process occurs in the body but AGEs can also be ingested from dietary sources, especially from foods cooked in high temperatures. AGEs are a significant source of oxidative damage in the body as they accumulate in tissues and generate ‘free radicals’ or what are known as reactive oxygen species (ROS). They also bind to a receptor called receptor for advanced glycation end products (RAGE) which triggers signaling pathways that lead to activation of NF-κB that drives major processes in CFC formation and progression. Excessive formation of AGEs and their accumulation in various tissues is associated with the development of chronic conditions such as diabetes and CFCs in humans.

Improving Blood Sugar Levels

Studies on people with type 2 diabetes have shown that ALA treatment can reduce serum lactate and pyruvate levels and improve glucose effectiveness. Lactate is the end product of fermentation and pyruvate is what glucose becomes once it enters a cell. One mechanism by which ALA may achieve this is by enhancing glucose uptake by the cell, achieved by increasing the number of glucose transporters on the cell membranes in the muscle and liver. This is essentially linked to CFCs since elevated levels of glucose and lactate in blood since one is required as a primary energy source for the growth of CFCs and the other is the end-product of glucose fermentation.

ALA has been shown to improve insulin sensitivity also by activating an enzyme called AMP-activated protein kinase (AMPK). AMPK functions as a sensor for fuel in a cell and is normally activated when the cellular energy (ATP) is depleted. Activated AMPK increases glucose uptake, fatty acid oxidation, and mitochondrial biogenesis. The blood glucose level is largely regulated by skeletal muscle tissue and lipid (fat) accumulation in muscle cells weakens insulin signaling of muscle cells and insulin resistance of the whole body. Activation of AMPK by ALA reduces lipid accumulation in skeletal muscles.

Alleviating Symptoms Caused by Conventional Treatments 

ALA has been found to be effective in reducing neuropathy (nerve pain) symptoms caused by chemotherapy. One of the most harmful effects that CFCs and conventional treatments cause is muscle and tissue wasting. This largely results from raised levels of proinflammatory cytokines and high energy demands of CFCs. Inflammation and weight loss due to tissue wasting have been found to correlate with CFC progression in people. Studies have shown that treating people suffering from CFCs with ALA can reduce pro-inflammatory cytokines IL-6 and TNFα and restore T cell function.

Targeting and Eliminating CFCs Including Stem Cells

Several studies have shown that ALA, especially when combined with other metabolic therapies such as IV vitamin C can eliminate CFCs with an efficacy comparable to chemotherapy agents but without causing harm to healthy cells. These therapeutic concentrations of ALA are achievable in humans with IV administration.

ALA has been shown to inhibit growth and promote cell death in CFCs by reversing their energy metabolism closer to that of a healthy cell. CFCs prefer to produce energy by aerobic glycolysis where glucose is converted to lactate. Persistent glycolysis in CFCs and accumulating lactate create an acidic tumor microenvironment which in turn leads to reprogramming of genes for tumor progression and metastasis. ALA has been found to decrease the glycolysis of CFCs and thereby the production of lactate. This may be due to the activation of pyruvate dehydrogenase by ALA. Pyruvate dehydrogenase is an enzyme in the glycolytic pathway that converts pyruvate to acetyl CoA thus preventing lactate formation from glucose. 

A sudden shift in energy metabolism can also cause cell death in CFCs. In one study, ALA was shown to inhibit cell growth, glucose uptake, and lactate formation in CFCs, while increasing apoptosis (cell death). CFCs that do not rely on oxygen in their energy production diminish their antioxidative defenses and are therefore more sensitive and vulnerable to oxidative stress. A sudden shift towards oxidative metabolism could result in the accumulation of reactive oxygen species (ROS) and oxidative damage, leading to cell death

In another study, ALA was found to increase the sensitivity of CFCs to radiation treatment, while also preventing the formation of stem cells and metastases triggered by radiation. ALA inhibited the release of matrix metalloproteinase enzymes MMP2 and MMP9 which are responsible for degrading protein structures between cells and therefore enable CFCs to detach and migrate to distant tissues. ALA also interrupted a signaling pathway that leads to epithelial-mesenchymal transition (generation of CFC stem cells) by inactivating NF-κB. 

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