Functional medicine: Focusing on imbalances in core metabolic processes

Evidence of probiotic effectiveness. Positive evidence in RCTs and meta-analyses suggests that strain-specific probiotics are beneficial for infectious gastroenteritis, persistent antibiotic-associated diarrhea, infant colic,⁵⁰ irritable bowel syndrome (IBS),^50,65Clostridioides difficile prevention,⁶⁶ inflammatory bowel disease (IBD),⁶⁷ ­radiation-induced diarrhea,^68,69 and nongastrointestinal conditions such as multiple sclerosis,⁷⁰ upper respiratory infections,⁵⁰ atopic dermatitis,^50,71,72 surgical site infections,^73,74 hyperlipidemia,^50,75,76 and nonalcoholic steatohepatitis.⁷⁷

However, because of knowledge gaps and low-quality evidence, the American Gastroenterological Association’s (AGA) 2020 Clinical Practice Guidelines recommend “conditional” use of strain-specific probiotics only for necrotizing enterocolitis prevention (in pre-term, low-birth-weight infants), antibiotic-induced C difficile prevention, and pouchitis.^53,54 Additionally, the AGA’s guidelines state that probiotics should only be used for C difficile infection, IBD, or IBS in a clinical trial and not used at all for infectious gastroenteritis.^53,54

Chelation

Chelation therapy is thought to inhibit ­metal-catalyzed oxidation reactions and inflammatory processes in tissues that lead to, and result from, accumulation of oxidative damage. While many FM practitioners recommend some form of chelation therapy, there is much controversy surrounding its use. Well-designed, large-scale clinical trials continue to emerge for what appears to be an old intervention with still uncertain clinical applications.

The first chelation agent, disodium ethylenediaminetetraacetic acid (EDTA), was synthesized in the early 1930s, but it was not until World War II that chelation therapy began with use of dimercaprol, a potent antidote for the arsenical chemical weapon lewisite. Disodium EDTA infusions were first used to treat angina pectoris in the mid-20th century,⁷⁸ and use accelerated in the early 21st century without a clear indication to treat CVD besides decades of anecdotes and case reports.⁷⁹ Strong epidemiologic data support a causal association between heavy metals (arsenic, lead, cadmium, mercury, and copper) and CVD,^80,81 but a distinct mechanism of action is not yet known.

Disodium EDTA was FDA approved in the 1950s for use in patients with hypercalcemia or ventricular arrhythmias from digitalis toxicity, but it was eventually withdrawn from the market in 2008, in part due to safety concerns following 3 deaths from severe hypocalcemia.⁸² These deaths were caused by inappropriate use related to rapid infusions, pediatric use, and in one case inadvertently administering disodium EDTA to a child instead of calcium EDTA (which can safely be bolused to treat pediatric lead toxicity).^82-85

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