The Role of Pigmented Rice in Reducing Cardiovascular Disease Risk: A Mini-Review of Animal and Human Studies
Diane S. Mendoza-Sarmiento, Alison M. Hill
Oct 2023 DOI 10.35460/2546-1621.2022-0089
Introduction
CVDs such as ischemic heart disease, stroke and hypertension are reported to be the leading cause of death in the Philippines.[1] Elevated lipids and glucose, and obesity are linked to the development of CVDs.[2] Alarmingly, there is an increasing prevalence of Filipinos with borderline-to-borderline high total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol and high to very high triglyceride (TG)[3]; high fasting glucose; overweight and obesity.[4] Lipid reduction is, therefore, an important target outcome for the prevention and management of cardiovascular diseases in this population.[5] An 11% reduction in TC can result in a 24% and 21% reduction in coronary heart disease incidence and mortality.[6] Further, a meta-regression analysis of statin and non-statin therapy trials (diet, bile acid sequestrants, ileal bypass and ezetimibe) reported for each 1 mmol/L reduction in LDL, the risk for a major vascular event was reduced by 23% for statins and 25% for non-statins.[7] For diet alone, the relative risk (RR) was 0.83 (95% CI, 0.72-0.96, P<0.05). In addition to dyslipidemia, hyperglycemia and overweight/obesity are also identified as risk factors for CVDs.[2] Hyperglycemia contributes to the formation of advanced glycation end products, which damage the endothelium, promoting the development of atherosclerosis and increasing the risk for hypertension and stroke.[8] Overweight and obesity is associated with low-grade chronic inflammation, which contributes to insulin resistance and atherosclerosis.[9] Obesity also results in structural and functional abnormalities, such as an increase in total blood volume, which increases stroke volume and cardiac output leading to ventricular hypertrophy, and alters the metabolic profile contributing to dyslipidemia, glucose intolerance and elevated blood pressure, all of which increase the risk for CVDs.[9,10]
Dietary patterns that are high in polyphenols are shown to reduce the risk for CVD mortality,[11] and dietary intervention with polyphenols is associated with improved CVD risk factors, including reduction of LDL, glucose and obesity.[12] Polyphenol intake is contributed mainly by non-alcoholic beverages such as coffee and tea, as well as fruits and vegetables.[11] While most Filipinos drink coffee, fruit and vegetable consumption is below recommendations.[13] Comparatively, cereals and cereal products account for 39% of food intake and are an essential component of the Filipino diet contributing to 70% of daily energy intake. [13] Polyphenol containing cereals, such as pigmented rice may provide an avenue for increasing intake in this population. Pigmented rice contains polyphenols, such as phenolics and anthocyanins, and are black, red or purple in color.[14] The color of black rice is primarily attributed to its anthocyanin content, while the color of red rice is due to proanthocyanidin, and both polyphenols contribute to the color of purple rice;[14] darker and stronger colors are associated with a higher total anthocyanin content.[15] These bioactive compounds have antioxidant properties.[14,16] This narrative mini-review will summarize the proposed mechanisms by which pigmented rice may provide cardioprotection. It also aims to explore the role of pigmented rice as an intervention in reducing lipids, glucose and weight for the prevention of CVDs.
Evidence from Animal Studies
Several animal studies have investigated the possible effect of pigmented rice on health through lowering lipids,[17–21], glucose,[17,22] and body fat,[17,18] and its associated mechanisms of action. Incorporation of pigmented rice (supplement form, extract, germinated) results in a reduction in TC [19–21] and, more importantly, in LDL [17,20,21] which is identified as the major lipid related to the development of CVDs.[5] Lowering TC and LDL may result from changes in the regulation of lipid metabolism. The study of Lo, et al.,[23] which provided germinated purple rice (20% of total diet composition) in the diet of ovariectomized Sprague-Dawley rats, resulted in decreased fatty acid synthase (FAS) and higher carnitoyl transferase (CPT) and β-oxidation activity, resulting in lower plasma TC, LDL and TG. Fatty acid synthase is an enzyme in adipose tissue and liver [24] that catalyzes de novo synthesis of fatty acids that are secreted in very low density lipoprotein (VLDL) or stored as lipid droplets along with TG in the liver.[25] Inhibition of FAS is postulated to reduce atherogenesis.[24] On the other hand, CPT is a rate-limiting enzyme that plays a significant role in fatty acid oxidation. Chung & Kang [17] who fed a high-fat diet including germinated, pigmented, giant embryo rice to obese mice also reported reduced FAS and increased CPT, along with decreased levels of apo-B, insulin and resistin and increased levels of adiponectin and apolipoprotein A-I (apoA-I). apoA-I is a major structural and functional component of HDL, while apolipoprotein B (apoB) is related to increased risk for CVDs as it is essential for the formation of VLDL, intermediate density lipoprotein and LDL,[26] and acts as a ligand for LDL receptors. Adiponectin, produced by adipose tissue but observed to be reduced among obese individuals, is related to increased high density lipoprotein (HDL), decreased TG, improved insulin sensitivity, reduced inflammatory cytokines and protection against atherosclerosis.[27] Using an obese mouse model, Kim, et al.[28] investigated the mechanism by which black rice (administered as an extract for eight weeks) reduced adipose tissue and improved lipids. They observed changes in transcription factors, peroxisome proliferator activated receptors (PPARs); consumption of black rice extract significantly upregulated PPAR-α and down-regulated PPAR-γ. PPARs play an important role in lipid and glucose metabolism; PPAR-α regulates β-oxidation of fatty acids and controls inflammatory processes, while PPAR-γ promotes adipogenesis (lipid storage).[29] These mechanisms observed in various animal studies and their potential effect on CVD risk factors (specifically lipid, glucose and body fat lowering) is summarized in Figure 1. H owever, results from animal trials do not always translate in humans as they typically supplement animals with greater doses than in humans and may not entirely capture the complexity of different human metabolic processes and interactions. Nonetheless, these studies test the plausibility of hypotheses and provide insight that can be further developed and used as a basis for human trials.
Evidence from Human Studies
Several human studies have examined the role of pigmented rice in reducing risk factors for chronic disease, specifically CVDs. Given the purported antioxidant activity of polyphenols, various studies evaluated whether consumption of pigmented rice led to increased circulating levels of polyphenols and antioxidant effects. Vitalini, et al. reported that consumption of cooked black rice (100 grams) resulted in higher circulating plasma phenols and flavonoids compared to brown rice among healthy adults.[16] Another study that compared the effect of a supplement containing a 10-gram black rice pigment fraction (BRF) with a white rice fraction (WRF) among coronary heart disease patients observed a significant increase in anthocyanin levels after consumption of the BRF compared to WRF.[30] Both studies observed an increase in polyphenol levels 30 minutes after ingestion of pigmented rice and peaking at 120 minutes. Further, increased antioxidant activity was also observed within 30 minutes, peaking from 60-120 minutes and lasting up to 150 minutes.[16,31] These studies, together with the results from animal studies, contribute to establishing the potential benefits of pigmented rice consumption on chronic diseases through its antioxidant capacity primarily contributed by polyphenols.
The results from recent human studies investigating the effect of pigmented rice on lipid levels are inconsistent. Studies by Joo, et al.,[32] Kim, et al.,[33] Seesen [34] and Wang,[30] demonstrated a reduction in TC, LDL and TG following pigmented rice consumption, but were not significantly lower compared to control. Comparatively, a study by Syarief, et al.[35] showed a significant decrease in TC, LDL and TG after the intervention compared to the control. Table 1 presents the key characteristics of these studies and a summary of outcomes. Reductions in lipids ranged from 5 to 30 mg/dL for TC, 1.2 to 8.5 mg/dL for LDL, and 8 to 23 mg/dL for TG. Of the five studies mentioned, only two [33,34] included glucose as an outcome and one [33] included weight. The effects on glucose are also inconsistent. Kim, et al.[33] investigated the effect of energy restricted diets using meal replacement (including black or white rice) among premenopausal overweight-obese women, and reported an 8.2±11.6 mg/dL reduction in fasting glucose levels after six weeks of intervention, along with a significant reduction in weight (-6.75±1.91 kg). The black rice group lost significantly more weight compared to control; however, changes in glucose were not different between the groups. Seesen, et al.[34] reported a non-significant 2.7± 21.74 mg/dL increase in fasting glucose after intervention with black rice germ. Participants from both studies had normal fasting glucose levels at baseline.
A possible explanation for the inconsistencies in results was differences in the study population, duration and design of intervention (ie, with or without concurrent energy restriction), and the form of pigmented rice. Study duration ranged from 4 to 24 weeks, and although all studies used black rice, it varied in form (see Table 1). More pronounced benefit may be seen in individuals with elevated lipids and glucose. Nonetheless, these studies provide preliminary evidence for the possible effect of pigmented rice on lipids, glucose and weight, which may help prevent the development of CVDs.
Conclusion and Recommendations
Animal studies have identified several mechanisms by which pigmented rice may influence risk factors, such as changes to enzymes involved in pathways that regulate fatty acid synthesis, lipid metabolism, inflammation and insulin sensitivity. Several human studies have been conducted with inconsistent results, which may be due to differences in study design and the population investigated. A systematic review and meta-analysis are recommended for a more comprehensive synthesis of the body of evidence. Lastly, more controlled clinical trials are needed to provide additional empirical evidence on the impact of pigmented rice in reducing lipids, glucose and weight.
Conflict of Interest
The authors declare that there is no conflict of interest in the conduct of this review.
Funding
The review did not receive any specific grant from any funding agency in the public, commercial or non-profit sectors.
Author’s Contribution
D.M-S: Review conception, organization, and execution, and review manuscript preparation.
A.H: Review conception, organization, and execution, and review manuscript preparation.
-
Philippine Statistics Authority. Causes of deaths in the Philippines (Preliminary): January to December 2021 [Internet]. Philippine Statistics Authority; 2022 [cited 2022 Aug 3]. Available from: https://psa.gov.ph/content/causes-deaths-philippines-preliminary-january-december-2021
-
Mozaffarian D, Wilson PWF, Kannel WB. Beyond established and novel risk factors: Lifestyle risk factors for cardiovascular disease. Circulation . 2008 Jun 10;117(23):3031–8.
-
Food and Nutrition Research Institute-Department of Science and Technology. Philippine Facts and Figures 2013: 8th National Nutrition Survey, Clinical and Health Survey. FNRI-DOST; 2015.
-
Food and Nutrition Research Institute-Department of Science and Technology. Philippine Nutrition Facts and Figures: 2018 Expanded National Nutrition Survey (eNNS). FNRI-DOST; 2020.
-
Lee Z-V, Llanes EJ, Sukmawan R, Thongtang N, Ho HQT, Barter P, et al. Prevalence of plasma lipid disorders with an emphasis on LDL cholesterol in selected countries in the Asia-Pacific region. Lipids Health Dis [Internet]. 2021;20(1):33. Available from: http://dx.doi.org/10.1186/s12944-021-01450-8
-
Grundy SM, Feingold KR. Guidelines for the management of high blood cholesterol. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dhatariya K, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000 [cited 2022 Dec 1]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK305897/
-
Silverman MG, Ference BA, Im K, Wiviott SD, Giugliano RP, Grundy SM, et al. Association between lowering LDL-C and cardiovascular risk reduction among different therapeutic interventions: A systematic review and meta-analysis. JAMA . 2016 Sep 27;316(12):1289.
-
Goldin A, Beckman JA, Schmidt AM, Creager MA. Advanced glycation end products: Sparking the development of diabetic vascular injury. Circulation . 2006 Aug 8;114(6):597–605.
-
Poirier P, Giles TD, Bray GA, Hong Y, Stern JS, Pi-Sunyer FX, et al. Obesity and cardiovascular disease: Pathophysiology, evaluation, and effect of weight loss: An update of the 1997 American Heart Association scientific statement on obesity and heart disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation . 2006 Feb 14;113(6):898–918.
-
Jastreboff AM, Kotz CM, Kahan S, Kelly AS, Heymsfield SB. Obesity as a disease: The Obesity Society 2018 Position Statement. Obesity . 2019 Jan;27(1):7–9.
-
Bo’ C, Bernardi S, Marino M, Porrini M, Tucci M, Guglielmetti S, et al. Systematic review on polyphenol intake and health outcomes: Is there sufficient evidence to define a health-promoting polyphenol-rich dietary pattern? Nutrients . 2019 Jun 16;11(6):1355.
-
Koch W. Dietary polyphenols—Important non-nutrients in the prevention of chronic noncommunicable diseases: A systematic review. Nutrients . 2019 May 9;11(5):1039.
-
Angeles-Agdeppa I, Sun Y, Denney L, Tanda KV, Octavio RAD, Carriquiry A, et al. Food sources, energy and nutrient intakes of adults: 2013 Philippines National Nutrition Survey. Nutr J . 2019 Dec;18(1):59.
-
Goufo P, Trindale H. Rice antioxidants: phenolic acids, flavonoids, anthocyanins, proanthocyanidins, tocopherols, tocotrienols, γ ‐ oryzanol, and phytic acid. Food Science and Nutrition . 2014;30.
-
Maulani RR, Sumardi D, Pancoro A. Total flavonoids and anthocyanins content of pigmented rice. Drug Invention Today . 2019;12(2):6.
-
Vitalini S, Sardella A, Fracassetti D, Secli R, Tirelli A, Lodi G, et al. Polyphenol bioavailability and plasma antiradical capacity in healthy subjects after acute intake of pigmented rice: A crossover randomized controlled clinical trial. JCM . 2020 Oct 5;9(10):3209.
-
Chung SI, Kang MY. Orract improves the lipid and glucose metabolisms in high-fat diet-red mice. Tundis R, editor. Oxidative Medicine and Cellular Longevity. 2021 Jan 15;2021:1–9.
-
Fatchiyah F, Safitri A, Rohmah RN, Triprisila LF, Kurnianingsih N, Nugraha Y, et al. The effect of anthocyanin of whole-grain pigmented rice attenuated visceral fat, cholesterol, LDL and PPARγ gene cascade in dyslipidemia rat. Systematic Reviews in Pharmacy . 2020;11(10):10.
-
Han HK, Choi SS, Shin JC, Chung HS. Lipid lowering effect of anthocyanin-pigmented rice bran in streptozotocin-induced diabetic male rats. JFN . 2008 Dec 31;13(4):276–80.
-
Purwaningsih H, Barrion ASA, Yee MG, Dizon JT, Hurtada WA. Lipid lowering effect of brown pigmented rice (Oryza Sativa L) in hyperlipidemic sprague dawley rats. International Journal of Agriculture Innovations and Research . 2018;6(6):10.
-
Zawistowski J, Kopec A, Kitts DD. Effects of a black rice extract (Oryza sativa L. indica) on cholesterol levels and plasma lipid parameters in Wistar Kyoto rats. Journal of Functional Foods . 2009 Jan;1(1):50–6.
-
Bae HJ, Rico CW, Ryu SN, Kang MY. Hypolipidemic, hypoglycemic, and antioxidative effects of a new pigmented rice cultivar “Superjami” in high fat-fed mice. J Korean Soc Appl Biol Chem . 2014 Oct;57(5):685–91.
-
Lo LMP, Kang MY, Yi SJ, Chung SI. Dietary supplementation of germinated pigmented rice (Oryza sativa L.) lowers dyslipidemia risk in ovariectomized Sprague–Dawley rats. Food & Nutrition Research . 2016 Jan;60(1):30092.
-
Batchuluun B, Pinkosky SL, Steinberg GR. Lipogenesis inhibitors: therapeutic opportunities and challenges. Nat Rev Drug Discov . 2022 Apr;21(4):283–305.
-
Jensen-Urstad APL, Semenkovich CF. Fatty acid synthase and liver triglyceride metabolism: Housekeeper or messenger? Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids . 2012 May;1821(5):747–53.
-
Walldius G, de Faire U, Alfredsson L, Leander K, Westerholm P, Malmström H, et al. Long-term risk of a major cardiovascular event by apoB, apoA-1, and the apoB/apoA-1 ratio—Experience from the Swedish AMORIS cohort: A cohort study. Basu S, editor. PLoS Med . 2021 Dec 1;18(12):e1003853.
-
Yanai H, Yoshida H. Beneficial effects of adiponectin on glucose and lipid metabolism and atherosclerotic progression: Mechanisms and perspectives. IJMS . 2019 Mar 8;20(5):1190.
-
Kim HW, Lee AY, Yeo SK, Chung H, Lee JH, Hoang MH, et al. Metabolic profiling and biological mechanisms of body fat reduction in mice fed the ethanolic extract of black-colored rice. Food Research International . 2013 Aug;53(1):373–90.
-
Grygiel-Górniak B. Peroxisome proliferator-activated receptors and their ligands: nutritional and clinical implications - a review. Nutr J . 2014 Dec;13(1):17.
-
Wang Q, Han P, Zhang M, Xia M, Zhu H, Ma J, et al. Supplementation of black rice pigment fraction improves antioxidant and anti-inflammatory status in patients with coronary heart disease. J Ma . 2007;7.
-
Anuyahong T, Chusak C, Thilavech T, Adisakwattana S. Postprandial effect of yogurt enriched with anthocyanins from riceberry rice on glycemic response and antioxidant capacity in healthy adults. Nutrients . 2020 Sep 24;12(10):2930.
-
Joo SH, Hahn C, Lim HK, Yoon KD, Yoon SH, Lee CU. An exploration of the Oryza sativa L. Cyanidin-3-glucoside on the cognitive function in older adults with subjective memory impairment. Psychiatry Investig . 2019 Oct 25;16(10):759–65.
-
Kim JY, Kim JH, Lee DH, Kim SH, Lee SS. Meal replacement with mixed rice is more effective than white rice in weight control, while improving antioxidant enzyme activity in obese women. Nutrition Research . 2008 Feb;28(2):66–71.
-
Seesen M, Semmarath W, Yodkeeree S, Sapbamrer R, Ayood P, Malasao R, et al. Combined black rice germ, bran supplement and exercise intervention modulate aging biomarkers and improve physical performance and lower-body muscle strength parameters in aging population. IJERPH . 2020 Apr 23;17(8):2931.
-
Syarief O, Fauziyah RN, Suparman S, Pramintarto G, Hendriyani H. The efficacy of fermented glutinous black rice (FGBR) snack to improve lipid profile among dyslipidemia subjects: A novel finding. International Medical Journal . 2020;25(08):9.
Figure
Figure 1. Summary of proposed mechanisms of action of polyphenols from pigmented rice on reducing risk for cardiovascular disease based on animal studies.
Each colored line represents the proposed mechanism of action targeting specific risk factors.
Table
Table 1. Characteristics of human studies investigating the effect of pigmented rice on lipids, glucose, and/or weight
Reference |
Design, Sample size |
Age (years) |
Sex |
Health Status |
Intervention |
Control |
Duration (Weeks) |
Outcome of interest |
Findings |
Joo, et al. 2019 [32] |
P-RCT, n=48 |
>50 |
M, F |
Subjective memory impairment |
Black rice, extract |
Crystalline cellulose |
12 |
TC, LDL, HDL, TG |
|
Kim, et al. 2008 [33] |
P-RCT, n=47 |
20-35 |
F |
Overweight to moderately obese |
Black rice, powder |
White rice |
6 |
TC, HDL, TG, Glucose, Weight, BMI, Body fat |
|
Syarief, et al. 2020 [35] |
P-RCT, n=52 |
>40 |
F |
Metabolic syndrome |
Black rice, fermented |
NR |
4 |
TC, LDL, HDL, TG |
|
Seesen, et al. 2020 [34] |
P-RCT, n=62 |
65-74 |
M, F |
Elderly |
Black rice, germ |
NR |
24 |
TC, LDL, HDL, TG, Glucose |
|
Wang, et al. 2007 [30] |
P-RCT, n=60 |
45-75 |
M, F |
Coronary heart disease |
Black rice fraction, powder |
White rice |
24 |
TC, LDL, HDL, TG |
|
BMI - body mass index; F - female; HDL - high density lipoprotein; LDL - low density lipoprotein; M - male; NR - not reported; NS - not significant; P-RCT - Parallel randomized controlled trial; TC - Total cholesterol; TG - triglycerides
Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License, which permits use, share — copy and redistribute the material in any medium or format, adapt — remix, transform, and build upon the material, as long as you give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use. You may not use the material for commercial purposes. If you remix, transform, or build upon the material, you must distribute your contributions under the same license as the original. You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by-nc-sa/4.0/.