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Cardiovascular disease (CVD) is one of the leading causes of morbidity and mortality globally, accounting for 30% of deaths (1) worldwide, in which blood lipid profile plays a major role. Elevated levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), very-low–density lipoprotein-cholesterol (VLDL-C), and triacylglycerol lead to progression of CVD and an increase of mortality. Among these, LDL-C is a major modifiable risk factor for atherosclerotic CVD (2), whereas, some types of the high-density lipoprotein cholesterol (HDL-C) are considered “good” cholesterol. Therefore, it is important to look at the ratio of TC to HDL-C in assessing the risk of CVD (3, 4). Along with lifestyle management, it is also vital to focus on a diet that can lower the risk of CVD by regulating metabolism and managing the lipid profile.

In developing countries, cereals typically occupy a major portion of the nutritionally unbalanced plate, which tends to be dominated by milled rice, maize, and refined wheat providing readily available carbohydrates. In addition, the so-called “junk food” and other unhealthy foods made from refined flour and fatty ingredients introduce large amounts of saturated fats into the body which, combined with sedentary lifestyles, can worsen the health of individuals. Lipid metabolism can be severely affected in individuals who are pre-diabetic, have type 2 diabetes mellitus, or other metabolic syndromes. Therefore, diet-based interventions for diabetes and other metabolic syndromes should contain ingredients that have a low glycemic index (GI) and the potential to correct metabolic abnormalities, such as deleterious lipid metabolism.

Millets are recognized as smart foods (5) as they fulfill the criteria of being “good for you,” “good for the planet,” and “good for the farmer,” Millets are traditional nutritious staple foods which can diversify staples and the overall diet when introduced, thereby playing a key role in controlling the levels of lipids in blood, managing metabolic disorders, such as diabetes and hyperlipidemia, and reducing the potential risk of developing CVD.

A recent systematic review and meta-analysis of low GI millets (including sorghum) and their effects on managing and reducing the risk of developing type 2 diabetes shows that millets have a beneficial effect on various outcomes, such as the fasting and post-prandial blood glucose levels, insulin index, and glycated hemoglobin (HbA1c) marker levels (6). This ability to manage and prevent diabetes may also help toward the management of hyperlipidemia. However, further, studies are needed to understand the effects of the consumption of millets on blood lipid management. This systematic review and meta-analysis are aimed at collating science-based evidence from randomized controlled trials and self-controlled clinical trials conducted through dietary intervention and cross-sectional studies on use of millets and their effects on lipid profile.

Review question: Does consumption of millet(s)-based foods help in managing blood lipid profile compared with regular, non-millet diets?

Finger millet, foxtail millet, barnyard millet, and/or a mixture of millets (finger millet and little millet) were used in the 19 studies (18–36) that were included in one or more outcomes of meta-analysis. It was observed that consumption of millet-based food for a duration varying from 21 days to 4 months had a significant reducing effect on TC, triacylglycerol, VLDL-C, and/or LDL-C levels. Two cross-sectional studies included in the systematic review documented millet consumption information for up to 2 years. The consumption of millets was either in the form of biscuits, burfi (sweet), porridge, buns, boiled with water (similar to rice), roti (flatbread), dumpling, or upma. The amount of millets provided to the intervention groups varied from 50 to 200 g (dry weight basis) either in one meal or divided into two meals per day.

The meta-analysis conducted on an outcomes-generated forest plot shows a significant reducing effect in TC levels after the consumption of a millet-based diet for 21 days to 4 months (p = 0.01) with SMD of −0.56, 95% class interval of −0.94 to −0.19, and I² value of 89% confirming the heterogeneity (Figure 2). Descriptive statistics conducted for 870 samples, and 21 observations from the 18 studies showed that the TC levels decreased by 8% from 189.5 ± 27.7 to 174.8 ± 28.9 mg/dl. Three studies demonstrated the reduction in TC levels from 215.8 ± 12.5 mg/dl (>200 mg/dl hence hypercholesterolemia) to 167.5 ± 3.2 mg/dl (<200 mg/dl hence normal).

The consumption of millets for a period of 21 days to 2 years had a significant reducing effect on (p < 0.01) triacylglycerol levels with SMD of −0.38 and 95% confidence interval (CI) of −0.47 to −0.28. As the heterogeneity was low (I² = 45%), the fixed effect model was used to interpret the results (Figure 3). Nonetheless, in both the fixed effect and random effect models, the effects were significant (p < 0.01). Descriptive statistics for 852 samples and 20 observations from the 17 studies showed a decrease in triacylglycerol levels by 9.5% from 154.3 ± 24.5 to 139.8 ± 23.5 mg/dl. There were four studies that demonstrated the reduction in hypertriacylglycerolemia (>150 mg/dl) to normal triacylglycerol levels (<150 mg/dl) after consumption of millets for 3 months with a mean reduction from 170.4 ± 17.2 to 128.6 ± 14.9 mg/dl (24.5% reduction) (18, 26, 28, 30).

The consumption of millet-based diets for long periods of time also had a significant reducing effect (p < 0.01) on LDL-C levels with I² value of 72% (moderate heterogeneity among studies) with SMD of −0.51 and 95% CI of −0.74 to −0.27 (Figure 4). The LDL-C levels from 834 samples in 18 observations from the 16 studies were 118.2 ± 23.9 mg/dl, compared with 106.7 ± 25.4 mg/dl at the baseline (10% reduction). Particularly, five studies demonstrated the reduction in LDL-C from a moderately elevated level of 116.5 ± 10.0 to a normal level of 92.6 ± 8.7 mg/dl. One long-term cross-sectional study showed a reduction from the high level of LDL-C (160.1 ± 26 mg/dl) to the moderately high level (140.1 ± 16.5 mg/dl).

For VLDL-C meta-analysis, I² value was 0% indicating no heterogeneity between the studies. However, both the fixed effect and random effect models showed a significant reducing effect in VLDL-C levels with p<0.01 (Figure 5). It is evident from 521 samples, 12 observations of the 10 studies that VLDL-C levels decreased by 9.0% from 30.2 ± 6.0 to 27.5 ± 4.9 mg/dl.

In contrast to other outcomes, the HDL-C levels (Figure 6) had a significant increasing effect after consumption of millet-based foods for a long period (p < 0.01) with SMD of 0.32, 95% CI of 0.12–0.52. Descriptive statistics showed that HDL-C levels slightly increased (6.0%) from 43.4 ± 7.5 to 46.0 ± 7.6 as found in 763 samples in 18 observations from the 15 studies.

The ratio of TC to HDL-C was kept below 5 (ideal) by consuming barnyard millet–based meals for 28 days to two months (32, 35), where the TC:HDL-C ratio was reduced from 5.1 ± 0.14 to 4.2 ± 0.26.

Although, descriptive statistics showed a mean reduction in weight by 1.5 ± 0.4 kg among 208 study participants who consumed the millet-based diet, the effect on reduction was not statistically significant in a meta-analysis (p = 0.15). There were only four studies that measured systolic blood pressure, which showed a significantly reducing effect after consuming a millet-based diet (p < 0.01). Diastolic blood pressure showed a significantly reducing effect after consumption of millet-based diet (p < 0.01). BMI had significantly reducing effect by 7.0% after consumption of millet-based diets for 3–4 months (p < 0.05) with no heterogeneity observed among the studies (I² = 0%) and 95% CI of −0.34 to −0.0.02 (Figures 7–10).

Publication bias was assessed using the funnel plot, and the observed asymmetry was adjusted using the trim and fit model to account for the small sample size effect until symmetry was achieved (p < 0.0001).

Hypertension, hyperlipidemia, diabetes, and smoking are the main risk factors for atherosclerotic CVD (37, 38). A recent systematic review on the effects of millets in managing and reducing the risk of developing type 2 diabetes showed that millets have beneficial effects on diabetes by providing low GI meals, reducing fasting and post prandial blood glucose levels as well as the glycated hemoglobin level (HbA1c) (6). The current systematic review focused on the effect on blood lipids as another important beneficial outcome of millet consumption. The meta-analysis showed that the ingestion of low (46.7 ± 12.0%) GI millet-based food had significant reductions in the levels of TC, triacylglycerol, LDL-C, and VLDL-C. Among other factors, the levels of glucose (and other simple carbohydrates) and saturated fats, and inappropriately controlled diabetes and metabolic syndromes are the causes of hyperlipidemia (37). Millets, being a low-GI food (6), reduce the blood glucose available for the synthesis of triacylglycerols (27). Moreover, millets also reduced VLDL-cholesterol which is a carrier of triacylglycerol in plasma, thereby it further reduced the triacylglycerol levels. This implies that millets play a key role in reducing triacylglycerol levels.

Overall, the 17 studies demonstrated an average of 9.5% reduction in triacylglycerol levels, and particularly four of the studies (18, 26, 28, 30) demonstrated that the plasma triacylglycerol levels reduced from a hypertriglyceridemic (>150 mg/dl) condition to normal (<150 mg/dl) when a millet-based meal was consumed once a day for 3 months instead of the regular rice- and/or wheat-based diets. Although, two cross-sectional studies that recorded more than 2 years of millet consumption showed that there was a reduction (26, 28), further, long-term randomized controlled trials would be necessary to confirm this.

LDL-C is considered as a major risk factor for CVD (39). Even with medication, residual LDL-C is associated with the risk of CVD. In the current study, consuming millets was shown to significantly reduce the LDL-C levels, and long-term consumption resulted in efficient reduction (26), indicating that long-term consumption of millets can help manage LDL-C levels and reduce the risk of CVD.

Reduction in the levels of LDL-C, VLDL-C, triacylglycerol, and TC is associated not only with the consumption of low-GI millets that produce a low glucose response and reduce the availability of glucose for triacylglycerol formation (27), but also with the consumption of unsaturated fatty acids from millets. The content of unsaturated fatty acids (both mono- and poly-unsaturated) is 2–10 times higher in millets compared with refined wheat and milled rice (Table 2). Some millets have 2.5, 5.7, and 7.8 times more unsaturated fatty acids, especially poly-unsaturated fatty acids compared with milled rice, whole wheat, and refined wheat. Intake of unsaturated fatty acids helps maintain high HDL-C levels. In addition, intake of poly-unsaturated fatty acids, which are essential in our diet, helps in lowering LDL-C levels and thereby lowering the risk associated with CVD (41, 42). Therefore, it suggests that replacing milled rice and refined wheat flour with millets bearing low GI and high poly-unsaturated fatty acids will help in reducing the risk of CVD. In this systematic review, there was 6.0% increase in HDL-C levels after consumption of millet-based meals as compared with regular rice or wheat meals. Thus, there is a need for further long-term randomized controlled trials to assess the impacts on HDL-C levels over an extended period of time. It is also noted that the refining process of teff, a type of millet, decreases the unsaturated fatty acid content and increases the risk of CVD (43).

Diastolic hypertension is common in individuals with components of the metabolic syndrome such as diabetes and hyperlipidemia, and diastolic blood pressure is the best predictor for future risk of CVD (44, 45). Five studies (18, 21, 22, 26, 28) showed that the average diastolic blood pressure in 320 subjects was slightly higher (86.9 ± 1.8 mmHg) than normal (<80 mmHg) at the beginning of the intervention, which was later decreased by 5% (from 86.9 ± 1.8 to 82.7 ± 1.3 mmHg), along with a decrease in lipids, after consuming a millet-based diet for 3 months compared with a regular rice/wheat-based diet. This suggests that consumption of a millet-based diet and diversification of staples with millet will help in reducing the risk of hypertension and associated CVD.

Obesity is a major concern as it raises the risk of CVD and type 2 diabetes. There was no statistically significant reduction in weight observed in the meta-analysis (p = 0.15), although, there was a reduction in the mean weight by 1.5 kg in 3 months. This suggests that more long-term studies with a larger sample size are needed for further investigation. Moreover, not all the studies that reported BMI also reported the actual weight.

On the other hand, it was evident from eight studies that on average there was a 7.0% reduction in BMI (28.5 ± 2.4 to 26.7 ± 1.8 kg/m²) in initially overweight and obese people, showing the possibility of returning to a normal BMI range (<25). Among the eight studies, six were randomized controlled trials conducted for 3–4 months, whereas, two others were cross-sectional studies conducted for 1–2 years. In the randomized controlled trials, there was no heterogeneity (I² = 0.0%) observed between the studies, which could be due to the smaller number of studies, sample size, and the influence of geographical distribution (Asian population, mostly Indian). Moreover, there was no variation in effect size, with SMD of −0.18 for both fixed effect and random effect models. The result was significant both in fixed effect and random effect models (p < 0.05). Therefore, it was evident that millet-based food consumption can help reduce the degree of overweight and obesity (>30 BMI). In the open-label, self-controlled clinical trial by Ren et al. (21), they observed that a reduction in BMI to be associated with a significant reduction in body fat mass (from 22.1 ± 7.1 to 21.1 ± 7.2 kg) within 12 weeks of foxtail millet consumption compared with only regular diet with no significant reduction in body muscle mass, indicating that consumption of millet was particularly targeting the fat in the body. Another study also showed a significant reduction in body fat mass from 21.6 ± 0.96 to 20.92 ± 0.98 kg by consuming whole foxtail millet-based meals for 12 weeks compared with a regular diet (33).

Furthermore, studies also showed that consumption of millet-based foods caused satiety (32). Ren et al. (21) showed that consumption of foxtail millet for 12 weeks increased the blood leptin levels significantly (from 8.3 ± 6.4 to 9.6 ± 7.0 ng/ml), which is the indication of hunger suppression and reduced energy intake by altering the nervous system signals and blood glucose metabolism. The satiety is also due to slower gastric emptying time (32, 46, 47) and the high fiber content of millet (40). This characteristic may reduce sudden spikes in blood glucose levels, leading to decreased availability of glucose for triacylglycerol synthesis, thereby reducing triacylglycerol levels. This would need detailed research to further investigate and quantify the variables and impacts.

Hyperlipidemia is associated with inflammation, leading to lipotoxicity and progression of CVD. Some markers that might contribute to endothelial dysfunction include leptin, interleukin-6 (IL-6), and adiponectin. Potential tools for risk assessment include serum high-sensitivity C-reactive protein (hs-CRP), fasting insulin, tumor necrotic factor-α (TNF-α), IL-6, leptin, and adiponectin (48). A study conducted on foxtail millet consumption for 12 weeks (18) showed a decrease in inflammatory marker IL-6 from 6.2 ± 9.4 to 4.8 ± 5.5 pg/ml and TNF-α from 2.6 ± 5.5 to 1.4 ± 0.5 pg/ml. Another study on finger millet consumption for 12 weeks (18) showed a significant reduction in IL-6 (from 4.9 ± 0.7 to 1.60 ± 0.5 mmol/l) (p = 0.000) and TNF-α (from 7.8 ± 1.2 to 3.9 ± 0.6 mmol/l) (p = 0.016). However, Sobhana et al. (22) demonstrated that consumption of a millet-based diet for 3 months did not significantly reduce hs-CRP (from 0.45 ± 0.078 to 0.43 ± 0.064 μg/ml), which is not a significant reduction. More long-term studies are recommended to examine this effect. However, the reduction in IL-6 and TNF-α suggests that millet consumption can reduce inflammation caused by hyperlipidemia and diabetes.

Two studies examined the impacts of millets consumption on plasma antioxidant capacity. Hymavathi et al. (20) demonstrated significant increases in the levels of antioxidants such as superoxide dismutase from 79 ± 11 to 82 ± 12 U/ml, and reduced glutathione (GSH) level from 10.9 ± 2 to 11.9 ± 2 U/L, suggesting that consumption of finger millet could suppress stress levels in both diabetic and normal individuals. Consumption of millets for 8 weeks increased the ferric ion–reducing antioxidant power (19) from 679.5 ± 120.3 to 763.9 ± 105.3 (p < 0.05) and Trolox equivalent antioxidant capacity from 296.9 ± 122.8 to 431.0 ± 55.4 (p < 0.05). In other words, antioxidant capacity improved in healthy individuals upon consumption of millets. Similar studies should be conducted on pre-diabetic, diabetic, and hyperlipidemic individuals to understand the effects of tissue damage from metabolic syndromes.

In this systematic review, although, studies examined the impacts of millet consumption on blood lipid profile, none of the included studies focused on millet consumption and its impact on hyperlipidemia in other related disease conditions, such as non-alcoholic fatty liver disease (NAFLD), which is predicted to become a major cause of liver-related morbidity and mortality by 2030 (49). Consumption of whole grains increases the intake of unsaturated fatty acids and dietary fiber, which enhances the fullness or satiety value, which, in turn, could have a beneficial effect on reducing energy intake and hyperlipidemia, and reducing the risk of CVD and NAFLD (49). Further, research on long-term millet consumption and its association with inflammatory markers and reduction in hyperlipidemia, especially in NAFLD individuals, would help to construct dietary plans to reduce risks of development and progression of NAFLD and CVD.

The systematic review executed in this study provides a strong evidence that millet consumption can improve blood lipid profile and thus exerts beneficial effects on management and prevention of hyperlipidemia, reduction in high blood pressure, weight, and BMI as well as an overall reduction in associated risk of CVD. Millets should therefore be integrated into nutrition and health strategies, utilized to diversify staples across Africa and Asia, and promoted as broader solutions in food system reforms. Further, analysis, customized to the situation, should be undertaken to ensure that millets are appropriately integrated into initiatives for maximized effectiveness.

The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s.

SA and JK-P: conceptualization, methodology, data extraction, and writing. SA, RB, and TWT: methodology, data extraction, analysis, and interpretation. DIG, AR, and RKB: methodology, risk assessment, writing, and reviewing the manuscript until final stage. All authors contributed to the article and approved the submitted version.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.