Despite the great number of observations being made concerning cellular and the molecular dysfunctions associated with autism spectrum disorders (ASD), the basic central mechanism of these disorders has not been proposed in the major scientific literature. Our review brings evidence that most heterogeneous symptoms of ASD have a common set of events closely connected with dysregulation of glutamatergic neurotransmission in the brain with enhancement of excitatory receptor function by pro-inflammatory immune cytokines as the underlying mechanism. We suggest that environmental and dietary excitotoxins, mercury, fluoride, and aluminum can exacerbate the pathological and clinical problems by worsening excitotoxicity and by microglial priming. In addition, each has effects on cell signaling that can affect neurodevelopment and neuronal function. Our hypothesis opens the door to a number of new treatment modes, including the nutritional factors that naturally reduce excitotoxicity and brain inflammation.

Fluoride has long been known to influence the activity of various enzymes in vitro. Later it has been demonstrated that many effects primarily attributed to fluoride are caused by synergistic action of fluoride plus aluminum. Aluminofluoride complexes have been widely used as analogues of phosphate groups to study phosphoryl transfer reactions and heterotrimeric G proteins involvement. A number of reports on their use have appeared, with far-reaching consequences for our understanding of fundamental biological processes. Fluoride plus aluminum send false messages, which are amplified by processes of signal transduction. Many investigations of the longterm administration of fluoride to laboratory animals have demonstrated that fluoride and aluminofluoride complexes can elicit impairment of homeostasis, growth, development, cognition, and behavior. Ameliorative effects of calcium, vitamins C, D, and E have been reported. Numerous epidemiological, ecological, and clinical studies have shown the effects of fluoride on humans. Millions of people live in endemic fluorosis areas. A review of fluoride interactions from molecules to disease is necessary for a sound scientific assessment of health risks, which may be linked to the chronic intake of small doses of fluoride and aluminum from environmental and artificial sources.

Fluoride has long been known to influence the activity of various enzymes in vitro. Latterly it has been demonstrated that many effects primarily attributed to fluoride are caused by a synergistic action of fluoride plus aluminum. Fluorinated chemicals are of growing importance, with applications in medicine. Fluorine substitution has profound effects on the properties of organic compounds. The very high electronegativity of fluorine can modify electron distribution in the molecule, affecting its absorption, distribution and metabolism. Fluorine-containing drugs are used in medicine as anesthetics, antibiotics, anti-cancer and anti-inflammatory agents, psychopharmaceuticals, and in many other applications. The potential contribution of fluorinating pharmaceuticals to human fluoride exposure is discussed.

Fluoride has been employed in laboratory investigations since the early 20th century. These studies opened the understanding of fluoride interventions to fundamental biological processes. Millions of people living in endemic fluorosis areas suffer from various pathological disturbances. The practice of community water fluoridation used prophylactically against dental caries increased concern of adverse fluoride effects. We assessed the publications on fluoride toxicity until June 2020. We present evidence that fluoride is an enzymatic poison, inducing oxidative stress, hormonal disruptions, and neurotoxicity. Fluoride in synergy with aluminum acts as a false signal in G protein cascades of hormonal and neuronal regulations in much lower concentrations than fluoride acting alone. Our review shows the impact of fluoride on human health. We suggest focusing the research on fluoride toxicity to the underlying integrative networks. Ignorance of the pluripotent toxic effects of fluoride might contribute to unexpected epidemics in the future.

The continuous rise of autism spectrum disorder (ASD) prevalent in the past few decades is causing an increase in public health and socioeconomic concern. A consensus suggests the involvement of both genetic and environmental factors in the ASD etiopathogenesis. Fluoride (F) is rarely recognized among the environmental risk factors of ASD, since the neurotoxic effects of F are not generally accepted. Our review aims to provide evidence of F neurotoxicity. We assess the risk of chronic F exposure in the ASD etiopathology and investigate the role of metabolic and mitochondrial dysfunction, oxidative stress and inflammation, immunoexcitotoxicity, and decreased melatonin levels. These symptoms have been observed both after chronic F exposure as well as in ASD. Moreover, we show that F in synergistic interactions with aluminum’s free metal cation (Al3+) can reinforce the pathological symptoms of ASD. This reinforcement takes place at concentrations several times lower than when acting alone. A high ASD prevalence has been reported from countries with water fluoridation as well as from endemic fluorosis areas. We suggest focusing the ASD prevention on the reduction of the F and Al3+ burdens from daily life.

Magnolia bark is a highly aromatic herbal material obtained from Magnolia officinalis (and other species) of the family Magnoliaceae. In traditional oriental herbal medicine, particularly Chinese medicine, this drug is used for many purposes, especially as a mild tranquillizer. The principal active compounds are the biphenol compounds, magnolol and honokiol, together with other biologically active compounds, which exert numerous and diverse pharmacological actions. Recent research has produced further evidence for the mechanism of their anti-inflammatory, anti-oxidant, antimicrobial, and antitumour activities, and these will be outlined in this review.