Table 1.

Studies investigate the effect of unrefined sugar on biomarkers of inflammation- extracted data on study designs, interventions, the form of sugar, and the key conclusion

First author, year, country	Study design	Intervention	Sugar form	Results	Key conclusions	Quality assessment score
Singh N, 2009,[28] India	Randomized (5 groups), 180 days, each group of 10 Swiss male albino mice with an average weight of 30±3 g	Intervention: Arsenic (0.05 ppm) Arsenic (5 ppm) Arsenic (0.05 ppm) + Jaggery (250 mg/kg) Arsenic (5 ppm) + Jaggery (250 mg/kg) Control: Neither arsenic nor jaggery	Jaggery in distilled water	1. In the jaggery-supplemented arsenic-exposed groups, the serum levels of interleukin-1β, interleukin-6, and TNF-α were significantly decreased compared to arsenic alone treated groups 2. The levels of interleukin-1β, interleukin-6, and TNF-α were significantly higher in arsenic-treated animals than in control animals	Jaggery effectively antagonizes many of the adverse effects of arsenic due to the presence of vitamins, minerals, carotene, and polyphenols, which may help maintain the redox equilibrium within the body to minimize the molecular and cellular oxidative damage caused by arsenic	6/10
Sánchez- Tapia M, 2019,[29] Mexico	Randomized (18 groups), 4 months, each group 6 male Wistar rats	Intervention: C+10% S C+10% F C+10% G C+2.5% SG C+10% BS C+10% H C+10% SV C+1.5% SU HF+10% S HF+10% F HF+10% G HF+2.5% SG HF+10% BS HF+10% H HF+10% SV HF+1.5% SU Control: C+W HF+W	Brown sugar in drinking water	1. Rats fed with sucrose, sucralose, glucose, and fructose showed the highest expression of RNA and protein abundance of TLR4 and MyD88. While BS and honey had the lowest expression of that 2. The phosphorylation of JNK was increased by SV, sucralose, sucrose, and fructose in the presence or absence of fat in the diet 3. Only groups fed with a high-fat diet stimulated the expression of NF-κB by sucralose and, to a lesser extent, by BS. There was no stimulation of NF-κB by SG and H 4. The expression of the TNF-α gene increased by sucralose, SV, Sucrose, glucose, and fructose and to a lesser extent by SG, BS, and H	Since the intake of different sweeteners has various effects on the inflammatory state, the consumer should be aware of the type of sweetener and the fat content in the diet to prevent further metabolic complications	6/10
Elayaraja S, 2020,[30] China	Randomized (4 groups), 75 days, each group 60 healthy mono-sex tilapia	Intervention: T1: biofloc water (C: N12) T2: biofloc water (C: N15) T3: biofloc water (C: N20) Control: Dechlorinated, sand-filtered + UV satirized freshwater without JP	Jaggery powder as a carbohydrate source in biofloc water	1. The mRNA expression of LYS, TNF-α, and IL-1β were significantly increased in the biofloc-treated fish compared to the control 2. The target genes were upregulated in proportion to the different C: N ratios, as the highest observed in C: N20 group, followed by C: N15 and C: N12 3. The increment in the expression of IL-1β and TNF-α genes reflects the effectiveness of JB-BFT in modulating the immune response of tilapia and increase its resistance to bacterial infection	JB-BFT upregulates the immune gene expression profile, which robustly influences Nile tilapia’s innate immunity through the favorable innovation of various immune cells and enzymes. Thus, jaggery has been offered as a potential new carbon source with a unique property that satisfies all considerations of biofloc technology with high productivity and zero water exchange (eco-friendly)	7/10
Rahiman F, 2010,[31] South Africa	In vitro design using human whole blood cultures	Intervention: Stimulated (LPS/PHA) and unstimulated human blood cultures with various concentrations of sugar cane molasses Control: Stimulated (LPS/PHA) and unstimulated human blood cultures without molasses	Molasses in distilled water	1. Molasses did not affect interleukin-6, interleukin-10, and interferon-gamma secretion in stimulated whole blood cultures 2. Molasses increased IL-6 secretion by unstimulating whole blood cultures for all concentrations compared to controls 3. Molasses samples increased the IL-10 secretion by unstimulated whole blood cultures only at 200, 400, and 800 µg/ml concentrations compared to the controls 4. Molasses samples did not affect IF-γ synthesis in both stimulated and unstimulated samples	Molasses affects the cytokines regulating the hormonal and immune system and have inflammatory and anti-inflammatory potential. Thus, sugar cane molasses may have beneficial in promoting improved hormonal responses, but further research is suggested to conclude the results	13/18
Rahiman F, 2013,[32] South Africa	In vitro design using human whole blood cultures	Intervention: Stimulated (LPS/PHA) and unstimulated human blood cultures in the presence of various sweeteners (Artificial/natural) Control: Stimulated and unstimulated human blood cultures in the absence of sweeteners	Sweeteners in distilled water	1. Sugar cane molasses enhanced IL-6 levels in the presence and absence of LPS, while all artificial sweeteners suppressed IL-6 levels of stimulated cultures 2. Brown sugar showed no effect on IL-6 levels compared to the distilled water control 3. None of the artificial and natural sweeteners had significant effect on levels of IL-10 in the presence and absence of PHA 4. Two artificial sweeteners significantly decreased the IL-10 levels under stimulated conditions 4. None of the artificial and natural sweeteners had significant effect on IFN-γ levels in the presence and absence of PHA	The current article shows that artificial and natural sweeteners are not cytotoxic; however, they impact specific cellular pathways. The inflammatory potential of the sugar cane molasses may be favorable in defense against infective pathogens	15/18

C=Control diet, HF=High-fat diet, W=Water, S=Sucrose, F=Fructose, G=Glucose, SG=Steviol glycosides, BS=Brown sugar, H=Honey, SV=SG + sucrose, SU=Sucralose, JP=Jaggery powder, LP=Lipopolysaccharide, LPH=Phytohemagglutinin