Sprouted Grains as a Source of Bioactive Compounds for Modulating Insulin Resistance

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Sprouted grains offer a sustainable and environmentally friendly platform for enhancing the content of naturally occurring bioactive compounds such as GABA and polyphenols. These compounds have potential applications in the formulation of functional foods and nutraceuticals aimed at improving insulin sensitivity and preventing metabolic disorders. Their natural origin and health-promoting properties align with ongoing efforts to develop safe, food-based strategies for disease prevention.

Abstract

Sprouted grains are gaining attention as a natural and sustainable source of bioactive compounds with potential benefits in managing insulin resistance (IR), a hallmark of obesity-related metabolic disorders. This review aims to synthesize current findings on the biochemical changes induced during grain germination and their relevance to metabolic health. We examined recent in vitro, animal, and human studies focusing on how germination enhances the nutritional and functional properties of grains, particularly through the synthesis of compounds such as γ-aminobutyric acid, polyphenols, flavonoids, and antioxidants, while reducing anti-nutritional factors. These bioactive compounds have been shown to modulate metabolic and inflammatory pathways by inhibiting carbohydrate-digesting enzymes, suppressing pro-inflammatory cytokines, improving redox balance, and influencing gut microbiota composition. Collectively, these effects contribute to improved insulin sensitivity and glycemic control. The findings suggest that sprouted grains serve not only as functional food ingredients but also as accessible dietary tools for preventing or alleviating IR. Their role in delivering multiple bioactive molecules through a simple, environmentally friendly process highlights their promise in developing future nutrition-based strategies for metabolic disease prevention.

1. Introduction

1.1. Overview of Insulin Resistance (IR) and Its Association with Obesity

The global rise in obesity, defined as a body mass index (BMI) ≥ 30 kg/m², has reached pandemic proportions, contributing to a syndemic burden that includes glucose intolerance, insulin resistance (IR), and diabetes mellitus [1]. IR, or impaired insulin sensitivity, refers to a diminished biological response to insulin in key metabolic tissues such as the liver, skeletal muscle, and adipose tissue [2].

Adipose tissue dysfunction in obesity plays a central role in the pathogenesis of IR. Enlarged adipocytes release excessive free fatty acids, reactive oxygen species (ROS), and pro-inflammatory cytokines, which collectively lead to lipotoxicity and chronic low-grade systemic inflammation [3]. This obesity-induced inflammation disrupts insulin signaling via key molecular pathways, including Nuclear factor kappa B (NF-κB), suppressor of cytokine signaling (SOCS) proteins, c-Jun N-terminal kinase (JNK), Wingless-related integration site (Wnt), and Toll-like receptor (TLR) signaling [4].

Moreover, hypertrophic adipocytes are characterized by increased lipid content and lipolysis, decreased secretion of adiponectin (anti-inflammatory adipokine), and increased secretion of leptin (pro-inflammatory adipokine). Inflammatory stimuli such as tumor necrosis factor-α (TNF-α) and lipopolysaccharide (LPS) further impair adiponectin release while enhancing secretion of leptin, monocyte chemoattractant protein-1 (MCP-1), and interleukin-6 (IL-6). These changes are associated with altered mitogen-activated protein kinase (MAPK) signaling, including impaired p38 MAPK and JNK activation, and persistent extracellular signal-regulated kinase (ERK) and inhibitor of kappa B alpha (IκBα) activation [5].

1.2. Dietary Interventions as a Key Strategy for Managing IR

Given the limitations of pharmacotherapy in reversing IR, dietary intervention has emerged as a cornerstone strategy for prevention and management. Extensive evidence from epidemiological and clinical studies demonstrates the critical role of dietary patterns in modulating IR and metabolic syndrome (MetS).

In a Chinese cohort, participants in higher quartiles of the modern dietary pattern had significantly higher odds of MetS, mediated by IR [6]. Similarly, adherence to a Western dietary pattern was associated with increased risks of MetS (RR: 2.32; 95% CI: 1.34, 4.00), elevated IR (RR: 1.69; 95% CI: 1.07, 2.65), and reduced insulin sensitivity (RR: 0.57; 95% CI: 0.39, 0.84), while a prudent dietary pattern was associated with more favorable outcomes [7]. In light of these findings, plant-based dietary patterns have garnered growing attention for their preventive and therapeutic potential in IR. Diets rich in whole grains, legumes, fruits, vegetables, nuts, and other minimally processed plant-derived foods have been associated with improved metabolic outcomes and a reduced risk of type 2 diabetes mellitus (T2DM) [8].

Among children and adolescents, a higher Healthy Eating Index (HEI) 2015 score was inversely associated with IR risk, particularly in girls [9]. Specific dietary interventions, such as high-protein diets, have also shown greater efficacy than Mediterranean diets in improving IR and glycemic variability among morbidly obese women [10]. In addition, nutrient-specific strategies such as walnut supplementation have demonstrated modest benefits on Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and body weight, although other metabolic markers remained largely unchanged [11].

1.3. Definition and Characteristics of Sprouted Grains

Sprouted grains are whole cereal or pseudocereal grains that have undergone controlled germination under specific conditions of temperature, moisture, and time. This process enhances the nutritional quality and functional properties through enzyme activation and comprehensive metabolic changes [12,13].

The sprouting process can be applied to diverse grain types. Commonly sprouted cereals include barley (Hordeum vulgare), oats (Avena sativa), brown rice (Oryza sativa), wheat (Triticum aestivum), and sorghum (Sorghum bicolor), each offering distinct nutritional advantages. Nutritionally rich pseudocereals such as quinoa (Chenopodium quinoa), amaranth (Amaranthus spp.), and buckwheat (Fagopyrum esculentum) are also excellent candidates for sprouting [14]. Additionally, legumes including mung beans (Vigna radiata), soybeans (Glycine max), and black beans (Phaseolus vulgaris) contribute to improved protein quality and enhanced bioactive compound content when sprouted [13].

Sprouting is a food processing technique that harnesses the early stages of germination—typically up to radicle protrusion—to trigger enzymatic breakdown of macronutrients (e.g., starch, protein) and promote the biosynthesis of bioactive compounds. During germination, three distinct phases can be recognized: Phase I involves rapid water uptake that initiates metabolism; Phase II features limited water uptake but major metabolic activities, including synthesis of hydrolytic enzymes such as α-amylase, endoxylanase, and phytase; and Phase III is characterized by radicle emergence. In contrast to full germination, sprouting is deliberately halted during Phase II or early Phase III to optimize nutrient enhancement while preserving desirable textural properties [15].

According to the American Association of Cereal Chemists (AACC), malted or sprouted grains that retain all of their original bran, germ, and endosperm qualify as whole grains, provided that the sprout growth does not exceed the kernel length and nutrient integrity is maintained [12]. In addition to whole sprouted grains, various derivatives such as bran extracts and enzymatic hydrolysates are increasingly used in functional food formulations due to their concentrated bioactive profiles [16,17].

Detailed changes in the nutritional profiles and bioactive compounds of sprouted grains are presented in Section 3.

1.4. Emerging Interest in Sprouted Grains as a Functional Food for Improving Insulin Sensitivity

Recent research has highlighted sprouted grains as a promising functional food for improving insulin sensitivity and metabolic outcomes in obesity. Germinated brown rice (GBR), in particular, has attracted attention due to its enriched bioactive compounds—such as gamma-aminobutyric acid (GABA), γ-oryzanol, phenolic compounds, dietary fiber, and minerals—which exert antidiabetic effects by improving glycemic control, enhancing antioxidant activity, and modulating the gut microbiota [18].

In animal studies, GBR and brown rice reduced hyperglycemia, IR, and inflammation, with GBR specifically enhancing probiotic gut bacteria in high-fat diet-fed mice [19]. Clinical findings support these effects: GBR intake in T2DM patients led to reductions in fasting blood glucose, insulin, and serum branched-chain amino acids (BCAAs), and improved islet function, possibly through activation of pyruvate dehydrogenase and enhanced BCAA catabolism [20].

Additional benefits include improved short-chain fatty acid (SCFA)-mediated gut–organ signaling and reduced inflammation, highlighting the systemic effects of sprouted grain consumption [21]. Moreover, germination reduces anti-nutritional factors and enhances the inhibitory activity of α-amylase and α-glucosidase, enzymes key to postprandial glycemic control [22]. Synergistic anti-inflammatory effects have also been observed when combining sprouted wheat, oats (cv. ‘Chimene’, a high-protein winter variety), and bran/oat hydrolysates, showing potent inhibition of IL-6 and TNF-α [23]. Enhanced polyphenol content and reduced glycemic index (GI) have been documented in rehydrated rice containing sprouted buckwheat (cv. ‘Jin buckwheat No. 2’), which may help prevent glucose spikes [24]. Flavonoids from sprouted grains contribute to metabolic homeostasis by modulating lipid metabolism, reducing inflammation, enhancing insulin signaling, and improving gut microbiota [25].

This focused review explores the mechanisms by which bioactive compounds from sprouted grains modulate IR, integrating evidence from in vitro, in vivo, and clinical studies. Unlike previous reviews that have primarily addressed nutritional changes during germination, our work provides a mechanistic and translational perspective on harnessing sprouted grains for functional food development. Their sustainable and natural origin further supports growing interest in food-based strategies for preventing metabolic diseases.

While this review does not follow the formal structure of a systematic review, it offers several important strengths. The focused narrative format allows for the integration of mechanistic insights across diverse experimental models, providing a coherent synthesis of current knowledge. This flexibility also enables the inclusion of recent and emerging studies that may not meet strict systematic review criteria but offer valuable perspectives on bioactive compound functionality.

A primary limitation is the absence of quantitative meta-analysis, which may limit the ability to draw generalized effect estimates. In addition, although environmental factors such as geographical origin can significantly influence metabolite composition, most of the included studies did not report detailed information on the plant sources’ regional provenance. This limited our ability to assess how location might affect the efficacy or phytochemical profile of the studied grains. Furthermore, due to the heterogeneity of study designs and outcomes, direct comparative evaluation of therapeutic potential across different sprouted grains was not feasible.

Nonetheless, to maintain scientific rigor, we clearly defined our literature search strategy and inclusion criteria, and prioritized studies with mechanistic relevance to IR. Despite these limitations, we believe the review contributes meaningfully to the field by bridging molecular findings with practical applications in the context of metabolic health.

2. Methods and Materials

2.1. Literature Search Strategy

A comprehensive literature search was conducted using the PubMed database to identify relevant studies on the effects of sprouted (or germinated) grains on IR and related metabolic parameters. The search terms included combinations of the following keywords: “sprouted grains,” “germinated grains,” “obesity,” “insulin resistance,” “metabolic syndrome,” “bioactive compounds,” “nutrients,” “carbohydrates,” “fat,” and “lipids.”

Boolean operators (e.g., AND, OR) were used to enhance the sensitivity and specificity of the search. The searching strategy focused on titles and abstracts to identify studies relevant to the biological activity and health impacts of sprouted grains and their derived compounds. To ensure the quality and relevance of the selected literature, the following inclusion and exclusion criteria were applied.

2.2. Inclusion and Exclusion Criteria

2.2.1. Inclusion Criteria

• Peer-reviewed original articles or reviews published between 2020 and 2025 (as of June 2025);
• Studies focusing on sprouted or germinated grains and their influence on IR, glucose metabolism, or metabolic health;
• Articles examining bioactive compounds or the nutritional composition of sprouted grains relevant to obesity, IR, or MetS;
• Older articles (published before 2020) were also considered when recent studies were unavailable or when foundational mechanisms were needed to support key points in the discussion.

2.2.2. Exclusion Criteria

• Studies published in non-English languages;
• Conference abstracts, letters to the editor, or reports lacking primary data;
• Articles not directly related to IR or metabolic functions;
• Duplicate publications or studies lacking a clear methodology.

3. Nutritional and Bioactive Components of Sprouted Grains

Sprouting is a biochemical process that activates endogenous enzymatic systems within grains, leading to substantial alterations in both macronutrient and micronutrient profiles. Table 1 presents the sprouting conditions for various grains, demonstrating that specific temperature, humidity, and duration parameters result in significant nutritional enhancements. The biochemical mechanisms underlying these compositional shifts are detailed in Table 2, which categorizes the major transformations in proteins, carbohydrates, lipids, and bioactive compounds. These changes have important implications for metabolic health, particularly in the context of IR. Notably, sprouting is associated with enhanced enzymatic activities, including increases in protease and α-amylase, and a reduction in lipase activity [26]. This section outlines the major nutritional transformations in proteins, carbohydrates, and lipids during sprouting and their potential relevance to metabolic regulation. Also, the bioavailability of micronutrients, reduction of anti-nutrients, and the influence of the germination process on the concentration of biologically active compounds were discussed.

Table 1. Sprouting conditions for common grains.

Grain Varieties	Sprouting Conditions	Key Benefits	References
Red-pigmented rice (Oryza sativa L.)	Soaked and germinated at 25 °C for 30 h, 90% humidity	↑ Protein (9.4%), ↑ Fat (27%)	[27]
Coix seed (Coix lacryma-jobi L.)	Soaked at 36 °C for 10 h, germinated at 29 °C for 24h	↑ Soluble protein (32%), ↑ Free amino acids (41%)	[28]
Oat (Avena sativa L. cv. ‘Turquesa’)	Germinated at 25 °C for 5 days in darkness, 60% relative humidity	↑ Protein (14%), ↑ Lipids (26%), ↓ Total fiber (55%)	[29]
Quinoa (Chenopodium quinoa Willd., cv. ‘Choclito’, white)	Germinated at 25 °C for 72 h, 95% humidity	↑ Protein (11%), ↑ Fiber (21%), ↑ Magnesium (9%)	[30]
Quinoa (cv. ‘Pasankalla’, red)	Standard germination conditions * for 72 h	↑ Protein (11%), ↑ Fiber (17%), ↑ Iron (11%)	[30]
Quinoa (cv. ‘Collana’, black)	Standard germination conditions * for 72 h	↑ Protein (13%), ↑ Iron (26%), ↑ Magnesium (18%)	[30]

* Standard germination conditions refer to typical laboratory settings with adequate moisture, temperature (20–30 °C), and air circulation. Symbols: ↑ indicates increase; ↓ indicates decrease.

Table 1. Sprouting conditions for common grains.

Grain Varieties	Sprouting Conditions	Key Benefits	References
Red-pigmented rice (Oryza sativa L.)	Soaked and germinated at 25 °C for 30 h, 90% humidity	↑ Protein (9.4%), ↑ Fat (27%)	[27]
Coix seed (Coix lacryma-jobi L.)	Soaked at 36 °C for 10 h, germinated at 29 °C for 24h	↑ Soluble protein (32%), ↑ Free amino acids (41%)	[28]
Oat (Avena sativa L. cv. ‘Turquesa’)	Germinated at 25 °C for 5 days in darkness, 60% relative humidity	↑ Protein (14%), ↑ Lipids (26%), ↓ Total fiber (55%)	[29]
Quinoa (Chenopodium quinoa Willd., cv. ‘Choclito’, white)	Germinated at 25 °C for 72 h, 95% humidity	↑ Protein (11%), ↑ Fiber (21%), ↑ Magnesium (9%)	[30]
Quinoa (cv. ‘Pasankalla’, red)	Standard germination conditions * for 72 h	↑ Protein (11%), ↑ Fiber (17%), ↑ Iron (11%)	[30]
Quinoa (cv. ‘Collana’, black)	Standard germination conditions * for 72 h	↑ Protein (13%), ↑ Iron (26%), ↑ Magnesium (18%)	[30]

* Standard germination conditions refer to typical laboratory settings with adequate moisture, temperature (20–30 °C), and air circulation. Symbols: ↑ indicates increase; ↓ indicates decrease.

Table 2. Nutrient and bioactive compound changes during germination.

Category	Key Changes	Examples and Details	References
Proteins and Amino Acids	• ↑ Endogenous protease activity → hydrolysis of storage proteins • ↑ Water-soluble proteins • ↑ Free amino acids	• Soybean (Glycine max; ZD41, J58, JHD): 36 h germination → water-soluble protein +9–30% • Quinoa (Chenopodium quinoa): 7 d germination → total essential amino acids +7–14%	[31,32,33]
Carbohydrates and Fiber	• ↑ α-amylase activity → breakdown of starch • Preferential amylopectin degradation → Relative ↑ amylose • ↓ Viscosity and gelatinization temperature	• Coix seed (Coix lacryma-jobi L.) : 24 h germination → starch ↓ from 58.9% to 52.4% • Oat (Avena sativa L.): α-amylase ↑ from 0.3 to 48 U/g • Quinoa: 72 h germination → changes in total dietary fiber	[28,34,35]
Lipids and Fatty Acids	• Lipase-mediated hydrolysis → β-oxidation and energy supply • ↓ Lipase activity relative to other enzymes •↑ Polyunsaturated Fatty Acids (PUFA; especially n-3), ↓ Saturated Fatty Acids (SFA)	• Barley (Hordeum vulgare): ↑ stearic acid (C18:0) and α-linolenic acid (C18:3n-3), ↓ oleic acid (C18:1n-9) • Eight grains comparison: PUFA 46.9–75.6% (millet highest)	[36,37]
Micronutrient Bioavailability	• Degradation of antinutrients → ↑ extractability of vitamins and minerals • ↑ Water-soluble B-vitamins and fat-soluble vitamin E	• Oat: marked ↑ in thiamine and riboflavin • Quinoa (JQ-R2): riboflavin 4–5× increase at 36 h • Brown rice (Oryza sativa): ↑ α-tocopherol and tocotrienols at 96 h after seed soaking	[26,38,39]
Antinutrient Reduction	• ↓ Phytic acid, lectins, and trypsin inhibitors • ↑ Phytase activity → mineral solubilization	• Quinoa: germination → ↓ phytic acid → ↑ Ca, Zn, Fe bioavailability	[40,41]
Bioactive Compounds	• ↑ Gamma-Aminobutyric Acid (GABA), polyphenols, flavonoids, β-glucan • ↑ Antioxidant and anti-inflammatory activities	• Adzuki bean (Vigna angularis): GABA up to 674 ± 31 mg/kg → improved glucose and weight regulation in mice • Oat: β-glucan +14–37% → Histone Deacetylase 3(HDAC3)/ Nuclear factor kappa B (NF-κB) pathway modulation • Red rice (Oryza sativa): flavonoids +20%, DPPH/ABTS activity ↑ 1.0–1.4×	[26,27,42,43]

A complete list of abbreviations is provided in the Abbreviations section. Symbols: ↑ indicates increase; ↓ indicates decrease; → indicates the resulting effect.

Table 2. Nutrient and bioactive compound changes during germination.

Category	Key Changes	Examples and Details	References
Proteins and Amino Acids	• ↑ Endogenous protease activity → hydrolysis of storage proteins • ↑ Water-soluble proteins • ↑ Free amino acids	• Soybean (Glycine max; ZD41, J58, JHD): 36 h germination → water-soluble protein +9–30% • Quinoa (Chenopodium quinoa): 7 d germination → total essential amino acids +7–14%	[31,32,33]
Carbohydrates and Fiber	• ↑ α-amylase activity → breakdown of starch • Preferential amylopectin degradation → Relative ↑ amylose • ↓ Viscosity and gelatinization temperature	• Coix seed (Coix lacryma-jobi L.) : 24 h germination → starch ↓ from 58.9% to 52.4% • Oat (Avena sativa L.): α-amylase ↑ from 0.3 to 48 U/g • Quinoa: 72 h germination → changes in total dietary fiber	[28,34,35]
Lipids and Fatty Acids	• Lipase-mediated hydrolysis → β-oxidation and energy supply • ↓ Lipase activity relative to other enzymes •↑ Polyunsaturated Fatty Acids (PUFA; especially n-3), ↓ Saturated Fatty Acids (SFA)	• Barley (Hordeum vulgare): ↑ stearic acid (C18:0) and α-linolenic acid (C18:3n-3), ↓ oleic acid (C18:1n-9) • Eight grains comparison: PUFA 46.9–75.6% (millet highest)	[36,37]
Micronutrient Bioavailability	• Degradation of antinutrients → ↑ extractability of vitamins and minerals • ↑ Water-soluble B-vitamins and fat-soluble vitamin E	• Oat: marked ↑ in thiamine and riboflavin • Quinoa (JQ-R2): riboflavin 4–5× increase at 36 h • Brown rice (Oryza sativa): ↑ α-tocopherol and tocotrienols at 96 h after seed soaking	[26,38,39]
Antinutrient Reduction	• ↓ Phytic acid, lectins, and trypsin inhibitors • ↑ Phytase activity → mineral solubilization	• Quinoa: germination → ↓ phytic acid → ↑ Ca, Zn, Fe bioavailability	[40,41]
Bioactive Compounds	• ↑ Gamma-Aminobutyric Acid (GABA), polyphenols, flavonoids, β-glucan • ↑ Antioxidant and anti-inflammatory activities	• Adzuki bean (Vigna angularis): GABA up to 674 ± 31 mg/kg → improved glucose and weight regulation in mice • Oat: β-glucan +14–37% → Histone Deacetylase 3(HDAC3)/ Nuclear factor kappa B (NF-κB) pathway modulation • Red rice (Oryza sativa): flavonoids +20%, DPPH/ABTS activity ↑ 1.0–1.4×	[26,27,42,43]

A complete list of abbreviations is provided in the Abbreviations section. Symbols: ↑ indicates increase; ↓ indicates decrease; → indicates the resulting effect.

3.1. Macronutrient Modifications During Sprouting

3.1.1. Modification of Protein and Amino Acid Contents

Sprouting activates endogenous proteases that initiate the hydrolysis of storage proteins, resulting in the breakdown of large polypeptides into smaller peptides and free amino acids [31]. This proteolytic activity not only alters the protein structure but also enhances protein solubility and digestibility, thereby improving the functional and nutritional properties of grains [44]. While the total crude protein content may remain relatively unchanged in some grain types, the increase in water-soluble proteins and free amino acids is consistently observed across various studies [32,45].

For example, in soybean varieties ZD41, J58, and JHD, germination for 36 h significantly increased water-soluble protein content by 30.52%, 9.34%, and 10.97%, respectively, despite minimal changes in total protein content [31]. Similarly, a seven-day germination process at 25 °C led to a modest 4% increase in protein concentration in other cereal grains [32]. However, a more pronounced effect is seen in the elevation of free amino acids, including essential ones such as lysine, threonine, phenylalanine, and tyrosine. Germinated yellow (‘Choclito’) and red (‘Pasankalla’) quinoa showed a 7.43% and 14.36% increase in total amino acids, respectively, with amino acid profiles approaching those found in high-quality protein sources such as eggs [33]. Additional studies have shown that sprouting improves both the protein content and amino acid balance in various grains, including oats and barley, and enhances sensory properties in sorghum-based beverages, indicating broader applicability in functional food development [26,36,46].

These findings suggest that protein remodeling through germination holds promise not only for improving nutritional quality but also for contributing to metabolic regulation in obesity-related IR.

3.1.2. Modification of Carbohydrates and Dietary Fiber

Carbohydrates, particularly starches, undergo significant structural and compositional changes during germination, primarily driven by the activation of hydrolytic enzymes such as α-amylase [47]. These enzymes catalyze the breakdown of complex polysaccharides into simpler sugars to meet the energy demands of the growing embryo. Germination tends to cause preferential degradation of amylopectin over amylose, thereby increasing the relative amylose content and altering starch properties, including gelatinization temperature and enthalpy [48]. In coix seed (Coix lacryma-jobi L.), for example, starch content decreased from 58.92% to 52.38% within just 24 h of germination, indicating rapid carbohydrate mobilization [28]. A similar trend was observed in oat grains, where α-amylase activity surged from 0.3 to 48 U/g, with only modest changes in proteolytic and lipolytic activities [34]. Structural changes at the microscopic and molecular levels have also been documented. In mung beans, germination at 25 °C for up to 72 h induced surface dents on starch granules, reduced molecular weight, and increased crystallinity, although the C-type crystalline pattern remained unchanged [35]. These changes affected physicochemical properties such as solubility, swelling power, and thermal behavior, leading to reductions in viscosity and gelatinization enthalpy.

The effect of germination on dietary fiber is more variable. Some studies report reductions in total, soluble, and insoluble fiber in oats (cv. ‘Turquesa’) after extended germination—55%, 44%, and 88% reductions, respectively, after 120 h at 25°C [29]. In contrast, other grains such as quinoa cultivars ‘Choclito’ (white), ‘Pasankalla’ (red), and ‘Collana’ (black) showed increased total fiber content after 72 h of germination [30].

Together, these findings suggest that germination modifies the carbohydrate matrix of grains in ways that improve digestibility and may reduce GI—features particularly beneficial for individuals with impaired glucose tolerance or IR. In addition, changes in dietary fiber content—whether increases or qualitative shifts—may influence gut fermentation, glucose absorption, and satiety. By facilitating starch breakdown into bioavailable forms and modulating fiber composition, sprouted grains may help regulate postprandial glucose responses and contribute to better glycemic control in at-risk populations.

3.1.3. Modification of Lipids and Fatty Acid Profiles

Storage lipids in cereals, primarily stored as triacylglycerols, undergo enzymatic hydrolysis during germination, generating non-esterified fatty acids and glycerol through the action of lipase [49]. These metabolites are subsequently oxidized via β-oxidation and the glyoxylate cycle, supplying energy for seedling growth. In sprouted oats, enzymatic activity shifts to favor proteolysis and amylolysis, while lipase activity declines [26].

Fatty acid composition also changes significantly during germination. In barley, sprouting results in increased levels of stearic acid (C18:0) and α-linolenic acid (C18:3n-3), along with a concurrent decrease in oleic acid (C18:1n-9), indicating a shift toward a more unsaturated lipid profile [36]. A comprehensive comparative study of eight sprouted grain varieties—including millet (Panicum miliaceum), quinoa (Chenopodium quinoa), rye (Secale cereale), wheat (Triticum aestivum), barley (Hordeum vulgare), oat (Avena sativa), buckwheat (Fagopyrum esculentum), and amaranth (Amaranthus spp.)—confirmed that germination not only increases total lipid content but also enhances the proportion of polyunsaturated fatty acids (PUFAs) [37]. Across all grain types, PUFA content ranged from 46.9% to 75.6% of total fatty acids, while saturated fatty acids comprised between 10.1% and 25.9%. Millet displayed the most favorable lipid profile, characterized by the highest PUFA and lowest saturated fat content. Sprouted oats demonstrated a 54.3% increase in total fat compared to their unsprouted controls, reflecting a substantial nutritional enhancement [37]. Furthermore, the omega-6 to omega-3 fatty acid ratios were particularly desirable in sprouted rye and barley, measured at 7:1 and 8:1, respectively. The dominant fatty acids present in the sprouted grains included linoleic, oleic, palmitic, α-linolenic, and stearic acids. These compositional changes not only improve the lipid quality of grains but also support their use as functional ingredients in dietary interventions aimed at improving lipid metabolism and insulin sensitivity in individuals with obesity-associated IR [37].

3.2. Enhanced Bioavailability of Micronutrients

Germination not only alters macronutrient profiles but also enhances the bioavailability of essential micronutrients, including vitamins and minerals. These improvements are largely attributed to enzymatic activation, degradation of antinutritional factors, and structural remodeling of the grain matrix, all of which enhance extractability and physiological relevance.

Significant increases in water-soluble B vitamins have been observed across various grains following germination. In sprouted oats, thiamine (vitamin B1) and riboflavin (vitamin B2) levels increased markedly, alongside improvements in β-glucan, amino acids, and antioxidant capacity [26]. Similar patterns were reported in quinoa, though with variety-specific responses. For instance, the JQ-R2 variety showed the highest thiamine content at 36 h (1.247 mg/100 g dry weight), while JQ-R2 and JQ-W4 exhibited 4-fold to 5-fold increases in riboflavin. Pyridoxine (vitamin B6) also increased in most varieties, although it was undetectable in certain ones (e.g., JQ-W3 and JQ-B2) at specific time points [38]. These findings underscore the importance of genetic background and germination timing in shaping vitamin profiles.

Germination also increases fat-soluble vitamin E compounds, particularly α-tocopherol, α-tocotrienol, and β-tocopherol, in brown rice cultivars (e.g., Guichao2 and Guanghong6) —especially at 96 h after soaking, the final stage of germination analyzed—when their contents reached the highest levels [39]. These lipid-soluble antioxidants contribute to the nutritional enhancement of sprouted grains and may support oxidative stress regulation and insulin signaling, which are relevant in metabolic diseases.

However, not all grains or vitamins respond positively to germination. A study on sorghum cultivar BRS 330 reported both beneficial and adverse effects: while riboflavin levels increased, thiamine and pyridoxine content declined significantly, with retention ranging from only 3.8% to 50.2%. Additionally, tocopherol and tocotrienol levels decreased, and certain flavonoids, such as 3-deoxyanthocyanidins and flavones, showed reduced stability during germination [50]. These divergent outcomes likely reflect the biochemical diversity of grain species, influenced by factors such as seed composition, enzymatic activity, and environmental conditions during cultivation and germination [51].

Taken together, these findings suggest that while germination can enhance the bioavailability of key micronutrients—notably thiamine, riboflavin, and vitamin E—the effects are highly grain- and context-dependent. A deeper understanding of these patterns is essential for developing sprouted grain-based products tailored to specific nutritional goals, such as managing IR and metabolic dysregulation.

3.3. Reduction of Anti-Nutrients and Improved Digestibility

Anti-nutritional factors in grains, such as phytic acid and lectins, are known to interfere with the absorption of essential nutrients by forming insoluble complexes with minerals or inhibiting digestive enzymes. These compounds limit the bioavailability of micronutrients like calcium, zinc, and iron, and can also impair protein digestion by binding to amino acid residues [41]. The inverse relationship between anti-nutrient content and nutrient bioavailability is well documented; higher levels of anti-nutrients consistently correlate with reduced digestibility and metabolic utilization of key nutrients [41].

Among these, thermosensitive anti-nutritional factors—including trypsin inhibitors, urease, lipoxygenase, and lectins—are particularly prevalent in legumes and cereals [52]. Germination is a well-established method for reducing the content of such anti-nutrients while simultaneously enhancing nutrient bioavailability. In quinoa (white, red, and black varieties), germination has been shown to increase phytase activity, leading to a significant reduction in phytic acid levels and a corresponding increase in the availability of calcium, zinc, and iron [40]. This enzymatic degradation of phytates is critical for improving mineral absorption, particularly in plant-based diets where phytic acid is abundant. By breaking down these inhibitory compounds, sprouting enhances both the nutritional quality and functional potential of grains—making them more suitable for populations at risk of micronutrient deficiencies or metabolic disorders such as IR [53,54].

3.4. Increased Bioactive Compounds

Germination profoundly alters the bioactive compound profile of grains, enhancing both their nutritional value and potential health benefits. Notably, sprouted oat powder from the Meeri variety, obtained after 96 h of germination at 18 °C, exhibited significant increases in bioactive compounds, including essential minerals, free phenolics, β-glucan, and GABA. These changes were accompanied by increased protease and α-amylase activity and decreased lipase activity, reflecting a broader reorganization of metabolic processes during germination [26].

A key bioactive compound enriched during germination is GABA, a non-protein amino acid synthesized from L-glutamic acid via glutamate decarboxylase [42]. GABA has been associated with improved insulin sensitivity, anti-diabetic and anti-inflammatory effects, appetite regulation, and modulation of obesity-related pathways [55,56,57].

Combined germination and fermentation can elevate GABA content up to 674 ± 31 μg/g without exceeding safety thresholds for biogenic amines such as histamine or phenylethylamine. Among the tested grains, sprouted oat (Avena sativa) exhibited the highest GABA concentration (443 ± 34 μg/g), followed by einkorn (Triticum monococcum) (347 ± 25 μg/g) and barley (Hordeum vulgare) (323 ± 24 μg/g). These increases highlight the grain-specific potential of germination to enhance GABA content while maintaining food safety [58]. Animal studies further support the functional relevance of these changes: GABA-enriched germinated adzuki beans (Vigna angularis, cv. ‘Pearl Red’) helped regulate body weight, stabilize blood glucose, and enhance glycolipid metabolism and gut microbiota composition in diabetic mice [59]. Additionally, maternal intake of GABA-enriched GBR during pregnancy and lactation improved gene expression related to energy balance and insulin sensitivity in offspring, while reducing pro-inflammatory markers [60].

Polyphenols and flavonoids, known for their antioxidant and anti-inflammatory properties, are also increased during sprouting. For example, the total flavonoid content in red-pigmented rice (Oryza sativa L.) increased from 22.89 μg/g to 27.80 μg/g after germination, while 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activities improved by 1.41-fold and 1.03-fold, respectively [27]. Similar trends have been observed in germinated black soybean (Glycine max) genotypes BS1 (Se-Um) and BS2 (Miryang 365), where phenolic and flavonoid levels were significantly elevated. These increases contributed to enhanced antioxidant capacity, as measured by DPPH, ABTS, and ferric reducing antioxidant power (FRAP) assays, as well as improved anti-inflammatory potential [61,62].

In addition, β-glucan levels in oats (cv. ‘Meeri’) increased by 14% (dehulled) and 37% (hulled) after sprouting at 14 °C for 60 h. Even when slightly reduced, β-glucan content remained above 2 g/100 g—sufficient for maintaining physiological benefits [26]. Importantly, β-glucan also exhibits potent metabolic regulatory functions. Recent studies have demonstrated that β-glucan consumption significantly alleviates colonic inflammation and IR by modulating the histone deacetylase 3 (HDAC3)/NF-κB signaling pathway, thereby highlighting its role in gut–metabolic axis modulation and anti-inflammatory action [43].

Collectively, these findings highlight germination as an effective strategy to enhance the bioactive compound profile of grains—particularly GABA, β-glucan, phenolics, and flavonoids—all of which are relevant to the prevention and management of IR, oxidative stress, and chronic inflammation.

3.5. Functional Food Applications of Sprouted Grains

Sprouted grains have gained significant attention in the functional food industry due to their enhanced nutritional profile and bioactive compound content compared to their non-sprouted counterparts. The sprouting process increases the bioavailability of essential nutrients such as vitamins (vitamin C and B-complex), amino acids, and minerals, while reducing anti-nutritional factors such as phytic acid and tannins, and simultaneously inducing the synthesis of health-promoting compounds, including GABA, phenolic acids, and antioxidants, which contribute to potential anti-diabetic, anti-inflammatory, and neuroprotective effects [13,63,64]. The food industry has increasingly incorporated sprouted grains into various product categories, including breakfast cereals, energy bars, baked goods (e.g., breads, cookies, crackers, muffins, tortillas), plant-based snacks, functional beverages, and nutraceutical products to meet consumer demand for nutrient-dense and functional foods [16,65]. Sprouted grain flours are particularly valuable as raw ingredients due to their improved nutritional profile and bioactive properties, making them suitable for developing foods targeted at specific health concerns, such as metabolic disorders and cardiovascular disease [64]. Consumer lifestyle shifts towards “healthy living and healthier foods” have driven food demand toward diets rich in bioactive molecules, with sprouted grains playing a crucial role as minimally processed, clean-label ingredients [13]. As consumer awareness of the health benefits of sprouted grains continues to grow, their application in functional food development is expected to expand further, representing a promising category of ingredients that bridge nutrition, functionality, and sustainability in modern food systems.

4. Mechanisms by Which Sprouted Grains Improve Insulin Sensitivity

The key mechanisms through which sprouted grains enhance insulin sensitivity are concisely summarized in

Table 3. Mechanisms by which sprouted grains improve insulin sensitivity.

Category	Mechanism Details	Metabolic Implications	References
Reduction of Postprandial Glycemic Response	• Inhibition of α-amylase and α-glucosidase → delayed carbohydrate hydrolysis → ↓ glucose absorption	• ↓ Postprandial glucose rise • ↑ Insulin signaling	[22,66,67,68]
Anti-Inflammatory and Antioxidant Properties	• ↓ Pro-inflammatory cytokines • ↑ Reactive Oxygen Species (ROS) scavenging via elevated polyphenols, ferulic acid, and antioxidants	• Protection of insulin signaling • ↓ Oxidative damage • Support glycemic control	[26,69,70,71]
Prebiotic Effects on Gut Health	• Modulation of gut microbiota [26,69,70,71] composition • ↑ Intestine barrier integrity • ↑ Short-Chain Fatty Acids (SCFA) production	• ↑ Metabolic homeostasis via the gut–liver axis • ↑ Insulin sensitivity mediated by SCFAs	[19,21,68,72,73]
Modulation of Lipid Metabolism	• ↑ Expression of hepatic genes involved in lipid metabolism • ↑ Fecal lipid excretion	• ↑ Improved lipid profiles • ↓ Dyslipidemia	[21,72,74]

A complete list of abbreviations is provided in the Abbreviations section. Symbols: ↑ indicates increase; ↓ indicates decrease; → indicates the resulting effect.

. These mechanisms include inhibition of carbohydrate-digesting enzymes, anti-inflammatory and antioxidant effects, modulation of insulin signaling pathways, regulation of gut microbiota, and improvement of lipid metabolism. By integrating findings from in vitro, in vivo, and clinical studies, Table 3 underscores the multifaceted biological actions of sprouted grains, supporting their potential as functional dietary components for managing IR and metabolic disorders.

4.1. Reduction of Postprandial Glycemic Response

One of the key mechanisms by which sprouted grains exert antidiabetic effects is through the attenuation of postprandial glycemic response, which is closely associated with improved insulin sensitivity [75]. This effect is primarily mediated by the inhibition of carbohydrate-digesting enzymes (e.g., α-amylase and α-glucosidase), which hydrolyze complex carbohydrates into glucose, thereby regulating the rate of glucose absorption in the small intestine [76]. Recent findings demonstrate that sprouted barnyard millet (Echinochloa esculenta, cv. ‘CO (KV)2’) significantly inhibits these enzymes, outperforming acarbose, a commonly used pharmacological inhibitor. Specifically, barnyard millet sprouts inhibited α-amylase activity by 87.2% during the intestinal phase, while microgreens showed 81.2% inhibition in the gastric phase. In α-glucosidase assays, enzyme activity was reduced by approximately 78–80% following treatment with digested extracts of sprouted samples, underscoring the role of polyphenols—particularly flavonoids—in enzymatic suppression [66]. Germination enhanced α-amylase and α-glucosidase inhibition across all grain types studied, with black wheat (Triticum aestivum, cv. ‘NABIMG-11-Black’) and barnyard millet (Echinochloa frumentacea, cv. ‘VL172’) exhibiting particularly strong activity while maintaining a low predicted GI (pGI < 55), even after processing [22]. In contrast, brown sorghum (Sorghum bicolor, cv. ‘VL Bhat 201’) required soaking followed by 48 h of germination to achieve optimal metabolic properties, including an in vitro protein digestibility (IVPD) of 68.7%, a GI of 51.03, and trypsin inhibitory activity of 23.17 TIU/mg [22].

Sprouting also enhances glycemic regulation at the systemic level. In a high-fat diet-induced mouse model of IR, supplementation with pre-GBR reversed hyperglycemia and improved insulin signaling in liver and skeletal muscle tissues by upregulating key components such as insulin receptor, insulin receptor substrate-1 (IRS-1), phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), AMP-activated protein kinase (AMPK), glucose transporter (GLUT)-1 and GLUT-4, as well as glucokinase (GCK) and peroxisome proliferator-activated receptor gamma (PPAR-γ) [67]. Likewise, dietary intervention with GBR significantly reduced fasting blood glucose levels, with an effective response rate of 62% in a human trial [68].

Collectively, these findings suggest that sprouted grains not only slow glucose absorption but also enhance intracellular glucose utilization via improved insulin signaling. This dual mechanism of action—inhibition of starch-digesting enzymes and upregulation of insulin signaling pathways—underscores the therapeutic relevance of sprouted grains as a functional dietary strategy for managing IR and metabolic disorders associated with obesity.

4.2. Anti-Inflammatory and Antioxidant Properties

Chronic low-grade inflammation and oxidative stress are key contributors to IR and the pathogenesis of MetS [77]. Germination has been shown to enhance the bioactivity of grains by increasing their anti-inflammatory and antioxidant potential—mechanisms that may underlie the observed improvements in insulin sensitivity following sprouted grain consumption.

4.2.1. Suppression of Pro-Inflammatory Cytokines

Germination promotes the accumulation of bioactive compounds such as ferulic acid, a phytochemical known for its potent anti-inflammatory and antioxidant properties. Ferulic acid acts not only as a free radical scavenger but also inhibits enzymes responsible for free radical generation and enhances the activity of endogenous antioxidant enzymes [69]. In a murine model of diet-induced obesity, three-month supplementation with a ferulic acid-rich extract from GBR significantly attenuated high-fat diet-induced systemic inflammation. This GBR extract improved lipid profiles and antioxidant status and reduced hippocampal expression of C-reactive protein (CRP) and TNF-α. Additionally, it upregulated PPAR-γ, indicating the activation of anti-inflammatory transcriptional pathways [70].

4.2.2. ROS Scavenging

The antioxidant capacity of grains is significantly enhanced by germination, which promotes the accumulation of polyphenolic compounds and activates antioxidant enzyme systems. In barley (cv. ‘GALIS’), antioxidant activity increased in a time-dependent manner, with longer germination durations producing higher radical scavenging capacity across multiple assays, including DPPH, FRAP, oxygen radical absorbance capacity (ORAC), and Trolox equivalent antioxidant capacity (TEAC) [71]. Sprouted oat (cv. ‘Meeri’) powder exhibited a nearly threefold increase in antioxidant capacity compared to its unsprouted counterpart, as measured by ORAC values (1744.27 ± 170.28 mg TE/100 g vs. 585.26 ± 53.71 mg TE/100 g) [26]. Further studies using DPPH and ABTS assays demonstrated that sprouts and microgreens of barnyard millet (cv. ‘CO (KV)2’) possess high bio-accessibility of antioxidant compounds during both gastric and intestinal digestion. Notably, the bio-accessibility of nitric oxide scavenging activity reached as high as 126% in microgreens, indicating potent in vivo antioxidant potential [66].

Taken together, these results suggest that germination enhances the anti-inflammatory and antioxidant properties of grains, offering significant protection against oxidative damage. This may help preserve insulin signaling integrity and support glycemic control in individuals with obesity-associated IR.

4.3. Prebiotic Effects of Sprouted Grains on Gut Health

The gut microbiota is a key regulator of host metabolism, inflammation, and insulin sensitivity [78]. Sprouted grains exhibit prebiotic properties by reshaping microbial composition, enhancing intestinal barrier integrity, and promoting the production of SCFAs.

Intervention with germinated brown and black rice increased the abundance of beneficial microbes such as Megamonas, Muribaculaceae, and Alloprevotella, while decreasing potentially pathogenic Veillonella [79]. Autoclaved GBR (cv. ‘Suijing 18’) further enhanced microbial diversity and selectively promoted the growth of Bacteroides, Faecalibacterium, Dialister, Prevotella, and Bifidobacterium, while suppressing pro-inflammatory taxa including Escherichia-Shigella [72]. GBR intake also modulated immune responses by increasing the regulatory T cell (Treg)/T helper 17 cell (Th17) ratio and lowering circulating levels of IL-6, LPS, and interleukin-8 (IL-8), all markers of systemic inflammation [68]. These changes were accompanied by a reduced Firmicutes/Bacteroidetes ratio and improvements in gut barrier integrity [73].

Additionally, germination stimulated colonic production of SCFAs, particularly isobutyric and valeric acids, which were inversely associated with IR and inflammatory cytokines such as TNF-α and MCP-1 [21]. Compared to white or non-germinated rice, GBR feeding led to increased Lactobacillus abundance and elevated SCFA levels in mice [19].

Collectively, sprouted grains reshape the gut ecosystem and promote SCFA production, contributing to improved metabolic homeostasis. Beyond their anti-inflammatory and insulin-sensitizing effects, SCFAs also support lipid regulation by inhibiting hepatic cholesterol synthesis and activating AMPK signaling [80], underscoring the gut–liver axis as a key mediator of the metabolic benefits of sprouted grains.

4.4. Modulation of Lipid Metabolism

Dyslipidemia is a hallmark of MetS and a major contributor to IR [81]. Germination alters the lipid composition of grains (see Section 3.1.3), thereby influencing host lipid metabolism through both hepatic and microbiota-mediated pathways. One indirect mechanism involves SCFAs produced during colonic fermentation of sprouted grains (see Section 4.3). SCFAs such as propionate and butyrate inhibit hepatic cholesterol synthesis and activate AMPK, a key regulator of lipid and energy metabolism [21,80].

Direct hepatic effects have also been observed. In T2DM rats, GBR improved lipid profiles by upregulating apolipoprotein A1 and low-density lipoprotein (LDL) receptor expression, leading to reduced hepatic lipid accumulation and enhanced insulin sensitivity [74]. In addition, several studies have reported increased fecal excretion of bile acids and cholesterol following germinated grain consumption, suggesting enhanced intestinal elimination of lipids as a complementary cholesterol-lowering mechanism [72].

Taken together, these findings highlight the capacity of sprouted grains to improve lipid metabolism through transcriptional regulation in the liver and modulation of gut microbiota-derived metabolites, contributing to metabolic health and reduced risk of dyslipidemia-related disorders.

5. Conclusions

Sprouted grains represent a promising dietary strategy for improving insulin sensitivity and preventing MetS. The germination process enhances the nutritional and functional profiles of grains by increasing the bioavailability of vitamins, minerals, and bioactive compounds such as GABA, polyphenols, β-glucan, and ferulic acid. These compounds contribute to improved glucose metabolism through multiple mechanisms, including inhibition of carbohydrate-digesting enzymes, enhancement of insulin signaling, suppression of pro-inflammatory cytokines, scavenging of ROS, modulation of gut microbiota, and regulation of lipid metabolism.

Evidence from in vitro, in vivo, and clinical studies consistently supports the metabolic benefits of sprouted grains, particularly in relation to glycemic control, inflammation, and lipid homeostasis. Given their accessibility, safety, and compatibility with whole-food-based diets, sprouted grains offer a practical and functional intervention for individuals at risk of or living with IR, obesity, and T2DM. To clarify the current evidence,

Table 4. Summary of reviewed studies on sprouted grains and insulin resistance.

Sprouted Grain	Key Bioactive(s)	Metabolic Effect(s)	Mechanistic Insight	Reference
Adzuki bean (Vigna angularis, cv. ‘Pearl Red’)	γ-Aminobutyric acid (GABA)	• ↓Fasting glucose • ↓Weight gain	• ↑GABA signaling • ↑ Shift in gut microbiota	[59]
Red rice (Oryza sativa)	Flavonoids	• ↑Antioxidant activity	• Supports glycemic control	[27]
Oat (Avena sativa, cv. ‘Meeri’)	β-glucan	• ↑ Histone Deacetylase 3(HDAC3)/ Nuclear factor kappa B (NF-κB) modulation	• ↑ Insulin signaling • Anti-inflammatory action	[26]
Quinoa (Chenopodium quinoa) White, red, and black varieties	Dietary fiber, Amino acids	• ↑Protein and fiber • ↓Phytic acid	• ↑ Nutrient bioavailability • ↓ Antinutrient interference	[40]

Selected abbreviations are written in full at first mention within the table. A complete list of abbreviations is provided in the Abbreviations section. Symbols: ↑ indicates increase; ↓ indicates decrease.

summarizes representative studies on sprouted grains, detailing their key bioactive compounds, metabolic effects, and mechanisms related to IR.

Future research should aim to optimize germination conditions for maximal health benefit, explore grain-specific bioactivities, and validate long-term effects in diverse populations. As interest in functional foods grows, integrating sprouted grains into nutritional guidelines may contribute meaningfully to the prevention and management of chronic metabolic diseases.