When food-grade strains of any of the aforementioned microorganisms are used, the mannitol and the organism itself are directly applicable to food products, avoiding the need for careful separation of microorganism and mannitol crystals. Although this is a promising method, steps are needed to scale it up to industrially needed quantities. Natural extraction
Since mannitol is found in a wide variety of natural products, including almost all plants, it can be directly extracted from natural products, rather than chemical or biological syntheses. In fact, in China, isolation from seaweed is the most common form of mannitol production. Mannitol concentrations of plant exudates can range from 20% in seaweeds to 90% in the plane tree. It is a constituent of saw palmetto (Serenoa).Traditionally, mannitol is extracted by the Soxhlet extraction, using ethanol, water, and methanol to steam and then hydrolysis of the crude material. The mannitol is then recrystallized from the extract, generally resulting in yields of about 18% of the original natural product. Another method of extraction is using supercritical and subcritical fluids. These fluids are at such a stage that no difference exists between the liquid and gas stages, so are more diffusive than normal fluids. This is considered to make them much more effective mass transfer agents than normal liquids. The super- or subcritical fluid is pumped through the natural product, and the mostly mannitol product is easily separated from the solvent and minute amount of byproduct.
From about 1940 to 1971, the medication was given to pregnant women in the incorrect belief that it would reduce the risk of pregnancy complications and losses. In 1971, DES was shown to cause clear-cell carcinoma, a rare vaginal tumor, in girls and women who had been exposed to this medication in utero. The United States Food and Drug Administration subsequently withdrew approval of DES as a treatment for pregnant women. Follow-up studies have indicated that DES also has the potential to cause a variety of significant adverse medical complications during the lifetimes of those exposed.The United States National Cancer Institute recommends women born to mothers who took DES to undergo special medical exams on a regular basis to screen for complications as a result of the medication. Individuals who were exposed to DES during their mothers pregnancies are commonly referred to as "DES daughters" and "DES sons". Since the discovery of the toxic effects of DES, it has largely been discontinued and is now mostly no longer marketed.