S-methyl cysteine sulfoxide and its potential role in human health: a scoping review

Figures & data

Figure 1. S-methyl cysteine sulfoxide (SMCSO; a.k.a. methiin) and its interplay between cruciferous and allium vegetables; SACSO S-allyl cysteine sulfoxide; PCSO S-propenyl cysteine sulfoxide. Source of structures provided: https://pubchem.ncbi.nlm.nih.gov/.

Figure 2. PRISMA flow diagram.

Table 1. Characteristics of experimental non-ruminant animal models (and one meta-analysis) exploring the effects of SMCSO on health-related outcomes (n = 13).

First author, Year (ref)	SMCSO dose, duration, (administration)	Model	Primary outcome	Results
(Fujiwara et al. 1972)	182 or 364 mg/kg/BW/day for 2 wk (supplemented in diet)	Male, Wistar rats, fed 1% cholesterol + 0.2% cholic acid diet, (n = 24)	Lipid profile	↓ blood cholesterol, cholesterol/phospholipid ratio↓ liver total cholesterol↓ liver lipids↓ free cholesterol (liver), total cholesterol in aorta (ns)
(Itokawa et al. 1973)	0.5% SMCSO, for 2 wk (supplemented in diet)	Male Wistar rats, fed 1% cholesterol + 10% coconut oil (hydrogenated) + 0.2% cholic acid) diet (n = 24)	Lipid profile	↓ plasma cholesterol, and cholesterol/phospholipid ratio↓ liver total cholesterol, free cholesterol, and cholesterol/phospholipid ratio↓ liver weight/body weight ratio (ns)↓ total liver lipids (ns)↓ aortic cholesterol (ns)↑ body weight (ns)↑ plasma phospholipid (ns)
(Kubodera et al. 1973)	Trial 1: 40 mg/100g/BW pre and post-irradiationTrial 2: 10 mg and 20 mg (dissolved/injected in distilled water)	Male X-irradiated Donryu rats, Trial 1: (n = 49) Male, ICR mice, Trial 2: (n = 70)	InflammationSurvival time	↑ kininogen↑ survival time
(H. S. Marks, Anderson, and Stoewsand 1993)	Pre-treated with 2 doses of 0.5 mmol SMCSO (48 h apart), then repeated 72 h later (via gavage)	Male, ICR mice, with B[α]P-induced MCPE genotoxicity (n = 49)	Cancer	↓ MCPEs
(Kumari, Mathew, and Augusti 1995)	200 mg/kg/BW/day, for 45 days (via gavage)	Male, alloxan-induced diabetic Sprague-Dawley rats (n = 30)	Lipid profileGlucose control	↓ blood glucose↓ total cholesterol in serum, and liver ↓ total cholesterol in the kidney (ns)↓ phospholipids and triglycerides in serum, liver, and kidney↓ VLDL, LDL, HDL, and atherogenic index↑ body weight (ns)↓ enhanced liver glucose-6-phosphatase↑ suppressed liver hexokinase and HMG CoA reductase ↑ fecal sterol excretion
(Kumari and Augusti 1995)	250 mg/kg/BW/day: once200 mg/kg/BW/day, for 45 days (via gavage)	Male, alloxan-induced diabetic Sprague-Dawley rats (n = 24)	Glucose control	↓ blood glucose and urinary glucose↓ area under curve and improved glucose tolerance↑ serum insulin↑ body weight (ns)
(Sheela, Kumud, and Augusti 1995)	Two studies:200 mg/kg/BW/day, for 1 month (via gavage), then as above and given glucose bolus	Male Alloxan-induced diabetic Sprague-Dawley rats, fed standard diet (Trial 1: n = 36, Trial 2: n = 72)	Glucose control	↓ blood glucose↑ liver glycogen↑ liver protein↑ serum protein (ns)- body weight (nil change)↓ post-prandial blood glucose
(Komatsu, Miura, and Yagasaki 1998)	25mg/ml/100g/BW/day (equivalent 250 mg/kg/BW/day) for 14 days (via gavage)	Hepatoma-induced hypercholesterolemic Donryu rats (n = 24)	Lipid profile	↓ total cholesterol (VLDL + LDL)↑ hepatic triglycerides↑ fecal bile acid excretion↑ Chol 7α-H - body weight, food intake, liver/hepatoma weights (nil change)- liver cholesterol, fatty acids, and cholesterol synthesis (nil change)
(Kumari and Augusti 2002)	200 mg/kg/BW/day, for 60 days (via gavage)	Male, alloxan-induced diabetic Sprague-Dawley rats (n = 24)	Glucose controlAntioxidant status	↓ blood glucose and urinary glucose↑ body weight↓ malondialdehyde, hydroperoxides, and conjugated dienes↑ superoxide dismutase and catalase- food intake (nil change)
(Kumari and Augusti 2007)	200 mg/kg/BW/day, for 45 days (via gavage)	Rats Male, Sprague-Dawley rats, fed 1% cholesterol diet (n = 48)	Lipid profile	↓ serum cholesterol, triglycerides, phospholipids↓ atherogenic index (total cholesterol/HDL)↓ free fatty acids in serum, liver, and heart↑ liver glycogen↑ fecal bile acids and sterols- blood glucose (nil change)↓ body weight↓ lipoprotein lipase, malic enzyme, and glucose-6-phosphate dehydrogenase↓ HMG CoA reductase (ns)- HDL (ns)
(de Castro et al. 2021)	200 mg/kg/BW/day, for 4 wk (via gavage)	STZ-induced diabetic rats (n = 26)	Glucose controlInflammation	↓ blood glucose↓ body weight (ns)↓ water and feed intakes (both ns)↓ duodenal wall Vref and Vtot↓ duodenal nuclear factor-ĸβ staining- BCL-2 and caspase-3 (nil change)
(de Lemos et al. 2021)	200 mg/kg/BW/day, for 30 days (via gavage)	Male STZ-induced diabetic Wistar rats (n = 25)	Lipid profileGlucose controlAntioxidant status	↓ blood glucose↓ triglycerides and VLDL ↑ total cholesterol and HDL-C (ns)↑ IL-10- IL-1β and IL-6 (nil change)↑ AST, ALT, and urea (ns), creatine (nil change)↑ superoxide dismutase and catalase↑ liver glycogen (staining)↓ pancreatic islet damage (staining)
(Kook, Kim, and Choi 2009)	200 mg/kg/BW/day for 28-45 days (n = 2 studies)	Rats	Glucose control	↓ blood glucose

All results were significant (p < 0.05) unless indicated as not significant (ns) or nil change.

ALT alanine transaminase; BW body weight; AST aspartate aminotransferase; B[α]P benzo[1] pyrene; BCL-2 B-cell lymphoma protein 2; Chol 7αH cholesterol 7α hydroxylase; HDL high-density lipoprotein; HMG CoA reductase hydroxymethylglutaryl coenzyme A reductase; ICR Institute of Cancer; lL interleukin; LDL low-density lipoprotein; MCPE micronucleated polychromatic erythrocytes; SMCSO S-methyl cysteine sulfoxide; STZ streptozotocin; VLDL very-low-density lipoprotein; Vref duodenal reference volume; Vtot = duodenal wall reference volume + lumen reference volume.

Table 2. Characteristics of in-vitro studies exploring the effects of SMCSO on health-related outcomes or mechanisms of action (n = 6).

First author, Year (ref)	SMCSO dose, duration	Model	Primary outcome	Results
(Sendl et al. 1992)	10^-3 M concentration	Rat liver homogenate, from hypercholesterolemic rats (cholestyramine-induced), exposed to purified sulfur compounds from garlic and wild garlic (n = 3)	Lipid profile	↓ cholesterol synthesis (ns)
(Higuchi, Tateshita, and Nishimura 2003)	10, 50, and 100 μM doses	Copper-induced human LDL oxidized cells	Antioxidant status	↓ lipid peroxide formation (dose-dependent)
(Bagiu, Vlaicu, and Butnariu 2012)	1.0 - >4.0 mg/ml (of Allium extracts)	Nine strains of Candida	Antibacterial activity	↑ anti-bacterial activity
(Yoshinari, Shiojima, and Igarashi 2012)	1 mM and 10 mM concentration	White preadipocyte cells (from rats)	Fat accumulation	↓ oil drop formation in adipocytes
(Tanaka, Shimada, and Nagaoka 2014)	10 mM concentration for 24 h	Measured mRNA of HepG2 human hepatoblastoma cells, following exposure to sulfur-containing amino acid	Lipid profile	↓ CYP7A1↑ HMG CoA reductase mRNA expression- LDLR (ns)- SREBP2 mRNA expression (ns)
(Nakayama et al. 2020)	60 μM and 180 μM doses (for PKA-expression)150, 300, and 500 μM (for synthesis)	Murine I-10 cells, exposed to cysteine sulfoxides (including SMCSO)	Steroidogenesis	↑ steroid synthesis (progesterone)↑ PKA-expression: doses at 60 μM and 180 μM↑ CREB expression (doses at 180 μM)

All results were significant (p < 0.05) unless indicated as not significant (ns) or nil change.

CREB cAMP response element-binding protein; CYP7A1 cholesterol 7α-hydroxylase; HMG CoA reductase hydroxymethylglutaryl coenzyme A reductase; LDLR low-density lipoprotein receptor; mRNA micro ribonucleic acid; PKA protein kinase A; SMCSO S-methyl cysteine sulfoxide; SREBP2 sterol regulatory element binding proteins.

Table 3. Characteristics of experimental human studies exploring the effects of SMCSO on health-related outcomes or mechanisms of action (n = 2).

First author, Year	SMCSO method, dose, duration	Design; Model	Primary outcome	Results
(Coode-Bate et al. 2019)	Study 1: (two groups) (1) 3 × 300 ml portions of GPN-rich broccoli soup weekly for 4 wk pre-surgery, or (2) control (normal diet) Study 2: participants given 1 single portion of GPN-rich broccoli soup	Two-arm, parallel, single-blinded, dietary supplementation. Study 1: men (n = 18) scheduled for TPB of the prostate; collected multiple biopsies, bloods, urine, and dietary intake Study 2: 3-phase cross-over study (with 2-week washout) involving healthy men and women, aged 18-65 years (n = 10); collected multiple urine and bloods over 24 h, and over a 2-week washout period	Differences in metabolic activity of SMCSO versus glucosinolates after consuming broccoli soup	SMCSO accumulated in prostate and peri-prostatic tissue (even in 1 man in the control group of Study 1) Plasma SMCSO was ∼1000-fold higher than GPN Only 6% of SMCSO excreted after 24 h, suggesting ∼90% metabolized in vivo
(Traka et al. 2019)	Randomized (3 groups) of 1 × 300 ml portion per week of either (1) low-GPN soup, (2) medium-GPN soup, or (3) high-glucoraphanin soup, over 12 months	Randomized, double-blinded, 3-arm parallel dietary interventionMen (n = 49) on active surveillance for prostate cancer; collected biopsies, bloods, and dietary intake	Changes in genetic expression in men undergoing active surveillance of prostate cancer, following a glucoraphanin-rich diet	Authors noted a significant inverse correlation between participants’ average 12-month SMCSO intake and WHO grade of prostate cancer (r = −0.34*)

* p < 0.05.

GPN, glucoraphanin; SMCSO, S-methyl cysteine sulfoxide; TPB, transperineal biopsy; WHO, World Health Organization.

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