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In fact, they initially adopt a proinflammatory phenotype and then later they acquire an anti-inflammatory profile to repair the tissue damage ( in vivo setting cannot be recapitulated by the static vision of M1-M2 polarization adopted in in vitro experiments, reached by stimulation with lipopolysaccharide (LPS)/interferon- (IFN-) or Interleukin (IL)-4/IL-13 or IL-10, respectively ( Reactive oxygen species (ROS) have been known for many years as fundamental for macrophages to kill invasive microorganisms through the oxidative burst mediated by NADPH oxidase ( Oxygen is a highly electronegative element that readily accepts electrons generated by normal oxidative metabolism within cells, thereby producing ROS

doi: 10.3389/fimmu.2018.01465 [DOI] [PMC free article] [PubMed] [Google Scholar] 129

Long-term clinical trials, including one that lasted four years, found no serious safety concerns at these levels.7 Most people tolerate ALA well, but some mild side effects can occur, especially at higher doses: Digestive issues like nausea, bloating, or stomach upset Skin reactions, including rash or itching Low blood sugar, especially when taken with diabetes medications These side effects are usually temporary and mild, but they appear more frequently at doses of 1,200mg/day or higher.3 4 Medication interactions ALA may interact with several medications and should be used with caution in these cases:39 Diabetes medications (e.g., insulin, metformin) ALA can help lower blood glucose, which may enhance the effects of diabetes drugs and increase the risk of hypoglycemia

Long-term safety data in humans is limited

Patellofemoral Joint Reaction Force : This force increases with greater degrees of knee flexion

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