Advantame vs Monosodium Glutamate: which is worse?

What is Advantame?

Advantame is the newest FDA-approved synthetic sweetener, approved in 2014. Like neotame, it is a structural derivative of aspartame but with a vanillin-derived substituent. It is approximately 20,000 times sweeter than sucrose — the most potent sweetener currently approved for food use in the US.

What is Monosodium Glutamate?

Monosodium glutamate (MSG) is the sodium salt of glutamic acid, a naturally occurring non-essential amino acid found in many proteins. It is used as a flavor enhancer to intensify umami (savory) taste. MSG was first isolated from seaweed in 1908 by Japanese chemist Kikunae Ikeda and has been used commercially since then.

Documented risks

Advantame: Advantame is the newest approved high-intensity sweetener with the least post-approval safety data. The FDA approval was based on extensive pre-market animal studies showing no significant toxicity, carcinogenicity, reproductive toxicity, or neurotoxicity at relevant doses. EFSA approved it for EU use in 2014, finding no safety concerns based on the submitted data. Like other synthetic sweeteners, advantame has not been studied for long-term effects in large human populations post-approval. The same gut microbiome and glucose tolerance concerns raised for other sweeteners (aspartame, sucralose, acesulfame K) have not been specifically studied for advantame, though the class-wide concerns are relevant. Given its 2014 approval date, independent long-term safety studies are still limited.

Monosodium Glutamate: MSG safety has been one of the most extensively debated food additive questions in the past 50 years. The 'Chinese Restaurant Syndrome' — a cluster of symptoms (headache, flushing, sweating, chest tightness) reported after eating Chinese food — was attributed to MSG in a 1968 letter in the New England Journal of Medicine. This set off decades of controversy. Multiple rigorous double-blind, placebo-controlled trials have failed to consistently demonstrate that MSG at doses present in food causes these symptoms when participants do not know whether they received MSG or a placebo. A comprehensive 1993 review by the FDA-commissioned Federation of American Societies for Experimental Biology (FASEB) found that while some sensitive individuals may experience symptoms at high doses (>3g of pure MSG on an empty stomach), the doses in typical food servings do not consistently produce symptoms in double-blind conditions. The FDA classifies MSG as GRAS (generally recognized as safe). EFSA's 2017 re-evaluation set an ADI of 30 mg/kg body weight per day, acknowledging that very high doses could affect neurological function but concluding typical dietary exposure is safe. Critics including Dr. Russell Blaylock and advocacy groups have argued that MSG is an 'excitotoxin' — a compound that overstimulates glutamate receptors in the brain and could cause neuronal damage. While glutamate is indeed a neurotransmitter and high-dose glutamate can cause neurotoxicity in animal models, the blood-brain barrier and normal metabolic regulation are generally considered sufficient to prevent dietary MSG from affecting brain glutamate levels. A 2018 EFSA re-evaluation noted that combined exposure to glutamates from all sources (including naturally occurring glutamate in protein-rich foods and other added glutamates E621-E625) could approach the new lower ADI in high consumers — a concern particularly for children with high processed food intake.