**4. Ginger and IDA**

The following sections will explore available evidence from in vivo, ex vivo, in vitro, and human clinical studies to elucidate the potential benefits of ginger for IDA and its associated clinical manifestations of altered iron metabolism. A summary of the research findings is presented in Table 2.

**Table 2.** A summary of the research findings on ginger's beneficial properties in its applications for iron deficiency anaemia and associated clinical manifestations of altered iron metabolism.



Abbreviations: bone morphogenetic protein (Bmp); GATA-binding factor 1 (Gata1); interleukin (IL); short-chain fatty acids (SCFA); tumour necrosis factor alpha (TNF-*α*).

#### *4.1. Iron Absorption Enhancement*

Prakash and Srinivasan [137] demonstrated in an animal study that various spices (ginger, capsaicin, and piperine) can improve the bioavailability of dietary iron. Groups of Wistar rats were fed diets containing different spices for eight weeks before being sacrificed. Everted segments of duodenum, jejunum, and ileum of small intestines isolated from these rats were examined for ex vivo iron uptake through incubation with a medium containing finger millet powder fortified with iron. Compared to the control group that was not fed with any spices, all spice-fed groups showed significantly higher iron uptake percentages (*p* < 0.05) in all sections of the small intestine. Ginger was the most potent among the three spices to increase iron uptake across all sections. The highest was 28.5 ± 2.09% uptake at the jejunum for ginger compared to 26.3 ± 1.30% for piperine, 22.6 ± 1.40% for capsaicin, and only 18.3 ± 0.39% for the control group. The suggested mechanism could be that the pungent spices altered mucosal permeation characteristics by increasing the absorptive surface [137].

Ginger can also be used as a food additive to enhance the bioavailability of non-haem iron. A study by Jaiswal et al. [138] compared the effects of iron bioaccessibility by adding various spices (ajwain, cumin, cinnamon, fennel, black pepper, and ginger) at 1 or 2% weight to wheat flour and different Indian bread formulations. The bioaccessibility of iron was measured through an in vitro dialysis method. Adding spices at 2% significantly enhanced iron bioaccessibility (*p* < 0.0001). Ginger, in particular, was shown to increase iron bioaccessibility in all food formulations by 2- to 3-folds. The authors attributed effects to the ascorbic acid and amino acids within ginger that favour iron absorption [138]. However, with its low vitamin C content (Table 1), iron bioaccessibility is likely to be assisted by other bioactive compounds in ginger.

The effects of ginger in enhancing iron availability have been confirmed in a human intervention study. Kulkarni et al. [139,140] conducted a human clinical study to demonstrate the potential use of ginger supplements in the treatment of IDA along with oral iron therapy. The study recruited 62 patients with anaemia following the WHO Hb cut-off levels, consisting of 12 males and 50 females, from a hospital in India. Their conditions were likely due to nutritional deficiency since those with chronic conditions, pregnancy, and blood donors were excluded. Participants were divided into two groups. The intervention group (n = 30) took 1.5 g of ginger powder with oral iron therapy, whereas the control group (n = 32) received only oral iron therapy as routine care. Fasting blood samples were collected at baseline and after 30 days. Pre- and post-treatment comparisons of haematological and iron parameters found significant increases (*p* < 0.05) in all parameters in both groups. However, the intervention group achieved a more remarkable improvement in percentage difference than the control group in Hb (+8.23% vs. +2.3%), iron status (+19.63% vs. +5.54%), total iron-binding capacity (−7.23% vs. −4.47%), and SF (+45.11% vs. +34.11%). However, the authors did not report whether there were significant differences in the mean differences between groups. Notwithstanding, based on the published sample size, means, and standard deviations, the p-values could be easily estimated. The mean difference between groups for serum iron levels was significantly different post-treatment (*p* < 0.007). Hence, the study demonstrated that ginger could assist in iron absorption and improve the efficacy of oral iron therapy for IDA.

The study by Kulkarni et al. [139,140] had several drawbacks. The first is its short duration of trial with only 30 days. Although patients with uncomplicated anaemia are expected to show improvement after 4 weeks of oral iron treatment, replenishment of iron store will take longer to achieve [123,124]. Secondly, the study did not track the adverse events experienced by the participants. Thus, there was no data on ginger's effects on any side effects of oral iron therapy. Thirdly, there could be selection bias in the study design as it is unclear how the group assignment was carried out. Hence, the results from this study need further validation with more well-designed clinical trials.
