FAO Nutrition Meetings
    Report Series No. 40A,B,C
    WHO/Food Add./67.29


    The content of this document is the result of the deliberations of the
    Joint FAO/WHO Expert Committee on Food Additives which met at Rome,
    13-20 December, 19651 Geneva, 11-18 October, 19662


    1 Ninth Report of the Joint FAO/WHO Expert Committee on Food
    Additives, FAO Nutrition Meetings Report Series, 1966 No. 40; 
    Wld Hlth Org. techn. Rep. Ser., 1966, 339

    2 Tenth Report of the Joint FAO/WHO Expert Committee on Food
    Additives, FAO Nutrition Meetings Report Series, 1967, in press; 

    Food and Agriculture Organization of the United Nations
    World Health Organization


    Synonyms                      D-Mannitol; Mannitol

    Chemical name                 1,2,3,4,5,6-Hexanehexol

    Empirical formula             C6H14O6

    Structural formula                    H   H   OH  OH
                                          '   '   '   '
                                  HOCH2 - C - C - C - C - CH2OH
                                          '   '   '   '
                                          OH  OH  H   H

    Molecular weight              182.17

    Definition                    Mannitol consists of D-mannitol and
                                  contains, after drying, not less than 98
                                  per cent. and not more then the
                                  equivalent of 102 per cent. of

    Description                   Mannitol is a white crystalline solid
                                  which is odourless and has a sweet

    Uses                          Sweetening agent, humectant,

    Biological Data

    Biochemical aspects

         D-mannitol occurs widely in nature in a variety of plants, algae
    fungi and certain bacteria. L-Mannitol does not occur naturally.
    Traces of mannitol have been identified occasionally in human urine
    (Pitkänen Pitkänen, 1964).

         D-mannitol has a slow rate of absorption from the intestinal
    tract and exerts laxative properties. The laxative threshold for man
    was found to lie between 10 and 20 g of D-mannitol per single dose
    (Ellis & Krantz, 1941). D-mannitol fed to dogs was excreted in large
    quantities in the urine (Jaffe, 1883). When 14C-D-mannitol was given
    at a rate of 240 mg/rat orally to non-fasted rats, about 50 per cent.
    of the radioactivity was recovered in the expired 14CO2 (Wick et
    al., 1954). In similar experiments, also using 14C-D-mannitol at a
    rate of 500 mg/kg body-weight, fasted rats oxidized 40 per cent. of
    the dose to 14CO2, non-fasted rats 68 per cent,; 9.74 per cent. was
    stored in the carcass; 1.28 per cent. in the liver and 6.32 per cent.
    was excreted in the urine (Gongwer, 1963). Feeding D-mannitol to rats

    and dogs led to a small but significant increase of liver glycogen
    (Carr et al., 1933; Todd et al., 1939; Silberman & Lewis, 1933; Carr &
    Krantz, 1938).

         When 14C-D-mannitol was administered to rats by i.p.injection,
    77-97 per cent. of the dose was excreted in the urine within 24 hours,
    and only 2-3 per cent. of the mannitol carbon was oxidized to 14CO2.
    Additional experiments using injection directly into the portal vein
    showed that mannitol could be oxidized by the liver only (Wick et al.,

         I.v. administered D-mannitol was completely cleared by the
    kidneys of 2 dogs at rates identical to inulin and creatinine (Smith
    et al., 1940). Mannitol did not elevate the blood sugar level of dogs
    upon i.v. injection at a rate of 22.5 g/dog (Todd et al., 1939.

         In man, i.v. administration of D-mannitol is practiced for
    induction of diuresis in oliguria or for forced diuresis in poisoning
    cases or to measure the extracelluar fluid compartment. There is an
    extensive literature available on these aspects (Milne, 1965;
    Widdowson et al., 1964). Following, the. i.v. injection of 10 g
    D-mannitol into man, 81 per cent. of the dose was excreted unchanged
    in the urine and up to 80 g, produced no toxic effect (Smith et al.,
    1940). Administration of 25 g of D-mannitol on 3 subsequent days to
    man did not significantly influence either the blood sugar level or
    the respiratory quotient (Ellis & Krantz, 1941). When 100 g D-mannitol
    was fed to man, the maximum rise in blood sugar level was 10 mg per
    cent. (Field, 1919).

    Acute toxicity


    Animal      Route       LD50                 References

    Mouse       oral        22 000               Gongwer, 1960
                i.v.        16 800               Robb, 1964
                i.p.        14 000-16 000        Deck et al., 1936
    Rat         oral        17 300               Gongwer, 1960

         Mice diet with signs of central nervous system depression and
    gastrointestinal tract mucosal damage; rats died with predominantly
    gastrointestinal tract signs (Gongwer, 1960; Gongwer, 1961).

    Short-term studies

         Rat. Groups of 20 male rats were fed 35 per cent. sucrose plus
    5 5 per cent. D-mannitol or 40 per cent. sucrose (control group) over
    a period of 3 months. The growth curves showed that D-mannitol was
    nutritionally inferior to sucrose (Ellis & Krantz, 1941). These
    results are in accordance with earlier findings, that mannitol is
    inferior to sucrose, as judged by weight gain of rats (Ariyama et al.,

         Monkey. Three rhesus monkeys were each fed 3 g of D-mannitol
    daily,. for 3 months. Two animals were employed as controls. No toxic
    signs nor pathological changes were observed (Ellis & Krantz, 1941).

         Man. The i.v. injection of 10 g of D-mannitol daily over a
    period of 1 month produced no significant changes in non-protein
    nitrogen, or CO2- combining power of blood, red cell count or renal
    function (Ellis & Krantz, 1941).

    Long-term studies

         No data are available.


         The poor absorption shown in the metabolic studies and a long
    clinical experience in man support the safety of D-mannitol.


         The many studies that have bean carried out in man provide a
    basis for evaluation.

    Estimate of acceptable daily intake for man

                                  mg/kg body-weight

       Unconditional acceptance        0-50

       Conditional acceptance          50-150


    Ariyama, T. & Takahashi, K. (1929) J. agric. chem. Soc. Japan, 5,

    Beck, F. F., Carr, C. J. & Krantz, J. C. jr (1936) Proc, Soc. exp.
    Biol. Med., 35, 98

    Carr, C. J., Musser, R., Schmidt, J. E. & Krantz, J. C. jr (1933) 
    J. biol. Chem., 102, 721

    Carr, C. J. & Krantz, J. C. jr (1938) J. biol. Chem., 124, 221

    Ellis, F. & Krantz, J. C. jr (1941) J, biol. Chem., 141, 147

    Field, C. W. (1919) Proc. Soc. Exp. Biol. Med., 17, 29

    Gongwer, L. E. (1960) Unpublished report submitted by Atlas Chemical
    Industries Ltd

    Gongweg L. E. (1961) Unpublished report submitted by Atlas Chemical
    Industries Ltd

    Gongwer, L. E. (1963) Unpublished report submitted by Atlas Chemical
    Industries Ltd

    Jaffe, M. (1883) Z. physiol. Chem., 7, 297

    Milne, M. D. (1965) Ann. Rev. Pharmac., 5, 125

    Pitkänen, E. & Pitkänen, A. (1964) Ann. med. exp. Fenn., 42, 113

    Robb, B. J. (1964) Unpublished report submitted by Atlas Chemical
    Industries Ltd

    Silberman, A. K. & Lewls, H. B. (1933) Proc. Soc. exp. Biol. Med.,
    31, 253

    Smith, W.W., Finkelstein, N. & Smith, H. W. (1940) J. biol. Chem.,
    135, 231

    Todd, W. R., Myers, J. & West, E. S. (1939) J. biol. Chem., 127,

    Wick, A. N., Morita, T. N. & Joseph, L. (1354) Proc. Soc. exp. Biol.
    Med.,85, 188

    Widdowson, E. M. & Dickerson, J. W. T. (1964) In: Comar, L. C. &
    Brommer, F. "Mineral Metabolism" New York-London, Vol. IIA p. 13

    See Also:
       Toxicological Abbreviations
       Mannitol (WHO Food Additives Series 21)
       MANNITOL (JECFA Evaluation)