Gastrointestinal reactions
Gastrointestinal adverse reactions were reported in 61 studies. Of these, 10 studies were randomized controlled trials 16, 30, 33, 55, 57, 59, 67, 79, 93, 95, 49 were cohort studies 2, 4, 7, 9, 18, 19, 23, 25– 27, 29, 35, 38– 43, 45, 46, 48, 50– 54, 58, 60, 66, 68, 69, 71, 73, 83, 85– 88, 90, 94, 97, 98, 101, 104, 105, 112, 113, 115, 118, and 2 were case series 84, 109. Most studies reported the number of patients experiencing an adverse reaction ( Table 1). Other studies reported adverse reactions observed in relation to the number of treatments given ( Table 2).
Table 1.  Gastrointestinal adverse reactions observed per number of patients.
Adverse reaction  Studies  Total patients, n  Patients with adverse reaction, n (%)  (%, min-max) †
Nausea (overall incidence)  [ 2, 18, 27, 33, 45, 46, 48, 53, 55, 57, 59, 60, 67, 84, 90, 93, 109, 118]  2214  257 (12)  (2–41) [ 55] - [ 48]
  Intravenous administration  [ 18, 27, 33, 46, 48, 53, 59, 90, 118]  1154  199 (17)  (2–41) [ 59] - [ 48]
  Transdermal application  [ 2, 45, 55, 57, 67, 93, 109]  1039  51 (5)  (2–32) [ 55] - [ 2]
  >1 administration route  [ 60, 84]  21  7 (33)  (29–36) [ 84] - [ 60]
Vomiting (overall incidence)  [ 2, 18, 27, 33, 46, 48, 55, 57, 59, 118]  1611  115 (7)  (0–64) [ 55] - [ 48]
  Intravenous administration  [ 18, 27, 33, 46, 48, 59, 118]  972  108 (11)  (2–64) [ 59] - [ 48]
  Transdermal application  [ 2, 55, 57]  639  7 (1)  (0–6) [ 55] - [ 2]
Nausea and vomiting ‡  [ 7, 38, 41, 54, 66, 69, 73, 85, 87, 115]  4529  591 (13)  (0–46) [ 66] - [ 73]
Abdominal cramps/stomach  ache (overall incidence)  [ 18, 26, 27, 39, 41, 54, 55, 59, 73, 85, 87, 93, 115]  1629  88 (5)  (1–52) [ 117] - [ 116]
  Intravenous administration  [ 18, 26, 27, 39, 41, 54, 59, 73, 85, 87, 115]  1253  72 (6)  (1–52) [ 18] - [ 26]
  Transdermal application  [ 55, 93]  376  16 (4)  (2–16) [ 55] - [ 93]
Halitosis/garlic-like breath  (overall incidence)  [ 4, 9, 16, 19, 29, 30, 35, 42, 43, 45, 50, 52, 55, 57, 58, 66– 68, 79, 83,  85, 88, 94, 95, 97, 98, 109, 112, 113]  5782  607 (11)  (0–100) [ 30] - [ 19, 43, 45, 83, 98]
  Intravenous administration  [ 16, 85, 94, 98]  239  14 (6)  (1–100) [ 85] - [ 98]
  Transdermal application  [ 4, 19, 29, 30, 42, 45, 50, 52, 55, 57, 58, 66, 67, 79, 83, 88, 95, 109,  112, 113]  5333  556 (10)  (0–100) [ 30] - [ 19, 45, 83]
  Intravesical administration  [ 35, 43, 97]  165  33 (20)  (1–100) [ 35] - [ 43]
  Oral administration  [ 9]  15  4 (27)
Diarrhea (overall incidence)  [ 2, 18, 41, 54, 57, 85, 93]  1107  27 (2)  (1–6) [ 85] - [ 93]
  Intravenous administration  [ 18, 41, 54, 85]  744  15 (2)  (1–6) [ 85] - [ 41]
  Transdermal application  [ 2, 57, 93]  363  12 (3)  (2–6) [ 57] - [ 93]
†Incidences of the adverse reactions have been calculated for all the individual studies. (min%–max%) are the lowest and highest observed incidence of an adverse reaction observed in the group of studies included.
‡ Nausea and vomiting are reported as one combined adverse reaction in some studies.
Table 2.  Gastrointestinal adverse reactions observed per number of treatments.
Adverse reaction  Studies  Total treatments, n  Adverse reactions observed, n (%)  (min%–max%) †
Nausea (overall incidence)  [ 40, 51, 68, 84, 105]  474  161 (34)  (16–57) [ 105] - [ 40]
  Intravenous administration  [ 40, 51, 68]  323  137 (42)  (41–57) [ 68] - [ 40]
  Intravesical administration  [ 105]  151  24 (16)
Vomiting ‡  [ 51, 68]  316  112 (35)  (29 - 71) [ 68] - [ 51]
Nausea and/or vomiting ‡  [ 25, 74, 101]  1557  220 (14)  (8–17) [ 25] - [ 101]
Abdominal cramps/stomach ache ‡  [ 51, 68, 101]  495  16 (5)  (1–19) [ 68] - [ 51]
Halitosis ‡  [ 68]  262  4 (2)
Diarrhea ‡  [ 51, 101]  233  2 (1)  (1–2) [ 101] - [ 51]
† Incidences of the adverse reactions have been calculated for all the individual studies. (min%–max%) are the lowest and highest observed incidence of an adverse reaction.
‡ Intravenous administration. The most commonly reported gastrointestinal adverse reactions were nausea and vomiting. The incidence of nausea seems to be less common with the transdermal administration of DMSO compared with intravenous administration. The majority of studies reported an incidence of nausea between 2–14%, with the exception of one study, reporting an incidence of 32% 2. In one study that failed to specify the dose, 8 of 42 patients reported nausea and anorexia, but the symptoms disappeared in five of the eight patients when the dose of DMSO was reduced 45.
Often the studies had short follow-up periods (less than 24 hours), especially when DMSO was used as a cryoprotectant. The study reporting the highest incidence of nausea had a follow-up period of 5 days 48, and the authors concluded that the high incidence of nausea observed might be due to the long follow-up period 48. In another article using the same data 119, it was suggested that the delayed nausea was due to gastrointestinal mucosal damage, and only the initial nausea could be related to DMSO, and therefore we decided only to include the data from the first 2 days after infusion 48.
Halitosis was reported in 29 studies 4, 9, 16, 19, 29, 30, 35, 42, 43, 45, 50, 52, 55, 57, 58, 66– 68, 79, 83, 85, 88, 94, 95, 97, 98, 109, 112, 113. In five studies, patients discontinued treatment due to halitosis 9, 45, 83, 94. In five studies, all patients experienced halitosis 9, 45, 83, 94. Unlike halitosis, other gastrointestinal side effects were reported more often when DMSO was administered intravenously, than transdermally or intravesically.
One study reported a severe case of nausea, vomiting, and abdominal cramps in one patient with an acute allergic reaction 59. However, in most studies the reported gastrointestinal reactions were transient and mild, often lasting only minutes to a couple of hours 16, 38, 41, 68, 85, 87, 90. Several studies reported a relationship between the dose of DMSO and the occurrence of gastrointestinal adverse reactions 26, 33, 53, 73, 83, 85.