Skip to main content
Download PDF
Download ePub

The effects of medicinal and food homologous substances on blood lipid and blood glucose levels and liver function in patients with nonalcoholic fatty liver disease: a systematic review of randomized controlled trials

Lipids in Health and Disease volume 22, Article number: 137 (2023) Cite this article

Abstract

Background

Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disorder worldwide. According to several previous studies, the treatment of patients with NAFLD using medicinal and food-homologous substances has consistent effects on the levels of blood lipids and blood glucose and liver function.

Objective

This systematic review was conducted to investigate the impact of medicinal and food homologous substances on blood lipid and glucose levels as well as liver function in patients with NAFLD.

Methods

A thorough search was conducted in eight databases, including China Science and Technology Journal Database (VIP), Chinese National Knowledge Infrastructure(CNKI), China Biomedical Literature Database (SinoMed), Wanfang Database, PubMed, Cochrane Library, Web of Science and Embase, for articles published from database inception until June 24, 2023. The methodological quality of the included studies was evaluated utilizing Cochrane Randomized Trial Risk Bias Tool, Edition 2 and GRADE methodology for assessment.

Results

A total of 13 randomized controlled trials, involving 829 patients with NAFLD, were included in the analysis, these studies included a total of 9 medicinal and food homologous substances. In the 13 studies, hawthorn (2), sea buckthorn (1), ginger (2), turmeric (4) (1 with chicory seeds), cinnamon (1), cardamom (1), purslane (1) and saffron (1) were included. The results of the included studies showed that medicinal and food homologous substances could improve high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TGs), fasting blood glucose (FBG) and liver enzyme levels in patients with NAFLD to a certain extent, but the effect of turmeric on TC, liver enzyme levels is controversial.

Conclusion

In patients with NAFLD, dietary intervention using medicinal and food homologous substances can ameliorate blood lipid and blood glucose levels and liver enzymes to some extent. In clinical work, medicinal and food homologous substances can be used to provide patients with NAFLD with a safe and effective dietary plan to help prevent and treat disease onset and progression.

Background

Fatty liver and hepatic steatosis are two cardinal features of NAFLD. Symptoms of NAFLD encompass anorexia, fatigue, dull abdominal pain, and satiety. The condition may progress to fibrosis, cirrhosis, and hepatocellular carcinoma, thus representing a significant etiology of end-stage liver disease that necessitates liver transplantation with considerable morbidity [1]. With changes in lifestyle and dietary patterns, the incidence of NAFLD is increasing annually and exhibiting a trend towards younger age groups. Currently, NAFLD has become an important public health problem affecting human health, and its disease and economic burden may increase in the next few decades [2]. In 2020, a global expert council suggested renaming NAFLD metabolic-associated fatty liver disease (MAFLD). Although the etiology of NAFLD remains elusive, the disease has been linked to a number of comorbidities, including metabolic syndrome, obesity, cardiovascular disease and diabetes [3, 4]. The development of NAFLD is significantly influenced by metabolic diseases, such as hypertension, dyslipidemia, and abnormal blood glucose levels [5]. To address this significant growth of NAFLD as a major medical concern, multidisciplinary research has shifted its focus to finding effective prevention and treatment methods. During NAFLD treatment, the main focus is on protecting the liver, lowering enzymes, regulating lipids, and lowering blood glucose while coordinating lifestyle, diet adjustments, and exercise. These measures are essential in the management of NAFLD, either for its control or to prevent its progression towards cirrhosis and hepatocellular carcinoma. However, the overall effectiveness remains poor due to the lack of targeted medications and patients' reluctance to modify their diet and lifestyle [6, 7]. In view of the increasing prevalence of NAFLD, it is imperative to discover safe, efficacious, affordable and simple methods for treating and slowing its progression.

Medicine and food with the same origin are defined as homologous. Furthermore, medicinal homologous food can be consumed as food or medicine to treat diseases [8]. When used to treat diseases, medicinal homologous foods have almost no hazardous side effects because they are mostly consumed as food in daily life [9]. The efficacy of these medicines is categorized into three types: upper, middle, and lower grades in Shennong's Materia Medica, which was written by numerous medical scientists in ancient China. Many drugs from the upper grade are still used frequently. These substances, including cassia bark (Chinese cinnamon), ginger, licorice, and wolfberry, are listed in the "Catalogue of Homologous Substances in Food and Traditional Chinese Medicine" issued by the National Health Commission [10, 11], and these medicinal and food homologous substances have certain effects on disease prevention and control [12, 13]. Based on the principle of food and medicine sharing the same origin in traditional Chinese medicine, this study proposes the hypothesis that medicinal and food homologous substances can improve the levels of blood lipids, blood glucose and liver function in patients with NAFLD and discusses their influence on the disease, aiming at providing safe and effective dietary treatment programs for patients with NAFLD to assist in the prevention and treatment of the disease.

Methods

This study was registered with PROSPERO (Registration Number: CRD42023384871) (https://www.crd.york.ac.uk/PROSPERO/#loginpage) and prepared following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [14].

Inclusion criteria

Participants (P): adults over 18 years who have undergone imaging or pathological examinations and have been diagnosed with NAFLD.

Intervention (I): The intervention group received dietary therapy intervention using substances in the 17th edition of the Homology Catalog of drug-containing foods [15] and the Notice on Piloting the substance Management of 9 substances, including Codonium codontiana [16], issued by China's National Health Commission and State Administration for Market Regulation on January 2, 2020 (It can be formulated into capsules through the process of grinding). It contains 95 medicinal and food homologous substances.

Control (C): The control group received conventional treatment or placebo.

Outcome indicators (O): (1)Blood lipids: serum HDL-C, LDL-C, TC, and TGs levels; (2)FBG levels; (3)Liver function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels.

Type of studies(S): prospective randomized controlled trials (RCTs).

Exclusion criteria (1) intervention substances are extracts of medicinal and food homologous substances; (2) studies for which data extraction was not possible; (3) repeat published research; and (4) reviews, notices, and conference papers.

Search strategies

In this study, two researchers (Yatian Jia and Yuexing Zhang) conducted a comprehensive literature search across multiple databases including CNKI, VIP, CBM, Wanfang, PubMed, The Cochrane Libraries, Web of Science and Embase by utilizing MeSH term "non-alcoholic fatty liver disease" along with its corresponding free words and the names of medicinal and food homologous substances. The search period covered from the inception of each database up until June 24, 2023. The search strategy is shown in the additional file 1.

Literature screening and data extraction

Two researchers (Yatian Jia and Yuexing Zhang) conducted independent literature searches and utilized EndNote20 literature management software to eliminate any duplicate data. Relevant articles were selected based on the analysis of their title and abstract, while irrelevant ones were excluded. The final literature for the analysis was shortlisted after reading the full texts and applying inclusion and exclusion criteria. Two researchers independently retrieved information from the literature, such as the name of first author, country and year of publication, research subjects, sample size, intervention, duration of the intervention, and outcome indicators. Any discrepancies during the screening and data extraction were resolved by consultation with a third researcher.

Risk of bias assessment

Two researchers (Qian Zhang and Yatian Jia) evaluated the Cochrane Randomized Trial Risk Bias Tool, Edition 2 (RoB 2), and the included literature was evaluated using evaluation criteria. Evaluation included the randomization process, deviation from expected interventions, missing outcome data, outcome measurement, and selection of reported outcomes [17]. Based on the results of RoB 2, the included articles were categorized as "high risk," "some concerns," or "low risk." In case of disagreement in the above process, the third researcher arbitrated, and a consensus was finally reached.

Evidence quality assessment

Two researchers (Qian Zhang and Yatian Jia) utilized the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) approach [17] to ascertain the certainty of the body of evidence. In this methodology, the initial rating for the quality of evidence from RCTs is high, but it may be downgraded to medium, low or very low if any limitations are identified in terms of bias, inconsistency, directness, imprecision and other aspects. However, evidence can be upgraded with large effects and clear dose–response relationships. If there is disagreement during this process, a third researcher will arbitrate until consensus is reached.

Results

Literature search results

An initial database search revealed 4,537 relevant publications (3,168 in Chinese and 1,369 in English). After eliminating 1,620 duplicate publications, 2,917 publications were retrieved. After reading the titles and abstracts, 2,875 publications were excluded due to the nonfulfillment of inclusion requirements. A total of 42 research articles fulfilled the inclusion criteria. After a second reading of the entire manuscript, 29 were excluded, and finally 13 articles were included in the study. Among the 13 articles, three [18,19,20] and 10 [21,22,23,24,25,26,27,28,29,30] were in Chinese and English, respectively. Figure 1 shows the literature screening procedure and results.

Fig. 1
figure 1

Flow chart of the screening and selection of literature

Full size image

Basic characteristics of the included literature

This study included a total of 829 individuals in 13 RCTs (Table 1). The medicinal and food homologous substances included hawthorn (n = 2), sea buckthorn (n = 1), ginger (n = 2), cardamom (n = 1), turmeric (n = 4), cinnamon (n = 1), purslane (n = 1), and saffron (n = 1). In one of the studies [26], three experimental groups were intervened separately using chicory, turmeric, and chicory + turmeric.

Table 1 Basic characteristics of the included literature
Full size table

Quality assessment of studies

Eleven studies [18, 20,21,22, 24,25,26,27,28,29,30] introduced the random allocation technique. Allocation concealment was implemented in six of the included studies [21, 25, 26, 28,29,30]. In seven investigations [21, 24,25,26,27,28, 30], participants, researchers, and outcome assessors were blinded, whereas in two studies [22, 23], only participants and researchers were blinded. Furthermore, all 13 studies [18,19,20,21,22,23,24,25,26,27,28,29,30] explained reasons for lost follow-ups or dropouts. The results of the methodological quality assessment for the included studies are presented in Fig. 2.

Fig. 2
figure 2

Assessment of risk of bias

Full size image

Quality of evidence

According to the GRADE manual, HDL-C was deemed as high-quality evidence, whereas TC, TG, LDL-C and ALT were all rated as moderate-quality evidence. FBG and AST received low-quality grades. The details of this assessment are presented in Table 2.

Table 2 GRADE evidence profile
Full size table

Effects of medicinal and food homologous substances on TC levels

Nine studies [18,19,20,21,22,23, 25, 28, 29] reported the effects of medicinal and food homologous substances on TC. These studies included 629 participants, 337 in the intervention group and 292 in the control group. In one study, 50 patients with metabolic fatty liver [18] were treated with Tartary buckwheat combined with sea buckthorn vinegar drink. The TC levels in the intervention group exhibited a decrease, although the difference was not statistically significant. In two studies [19, 20], hawthorn was administered for the treatment of NAFLD and demonstrated a significant effect on reducing TC levels. Ginger intervention [21] can significantly reduce TC levels; cinnamon and purslane [28, 29] have also been demonstrated to effectively reduce TC levels. One study [25] comprised three experimental groups: turmeric, chicory, and a combination of turmeric and chicory. In all three groups, a significant reduction in TC was observed. However, a separate study [23] found that the use of turmeric did not have a significant effect on TCl levels in patients with NAFLD. Similarly, the study on cardamom [22] showed no significant impact on TC levels in NAFLD patients.

Effects of medicinal and food homologous substances on TGs levels

Nine studies [18,19,20,21,22,23, 25, 28, 29] reported the effects of medicinal and food homologous substances on TGs. These studies involved a total of 629 participants, with 337 in the intervention group and 292 in the control group. In studies of hawthorn [19, 20], sea buckthorn [18], cardamom [22], turmeric [23] and cinnamon [28], the TGs levels of patients with NAFLD were significantly reduced. In the studies involving the three experimental groups [25], the intervention of turmeric alone or turmeric combined with chicory seed could significantly reduce TGs levels. However, no significant improvement was found in the studies of ginger [21] and purslane [29].

Effects of medicinal and food homologous substances on LDL-C levels

Nine studies [18,19,20,21,22,23, 25, 28, 29] have reported the effects of medicinal and food homologous substances, including hawthorn, sea buckthorn, ginger, cardamom, turmeric, chicory seed and purslane, on LDL-C levels; all of these substances significantly improved LDL-C levels.

Effects of medicinal and food homologous substances on HDL-C levels

Nine studies [18,19,20,21,22,23, 25, 28, 29] reported the effects of medicinal and food homologous substances on HDL-C levels; ginger, cinnamon, and purslane [21, 28, 29] did not exhibit a significant impact on HDL-C levels. In the turmeric study [23], the turmeric group exhibited a significant improvement in HDL-C levels compared to baseline. Another study on turmeric [25] found that both the turmeric group and the combined chicory seed-turmeric group showed a significant increase in HDL-C levels. In addition, hawthorn, sea buckthorn and cardamom exhibited significant improvements in HDL-C levels.

Effects of medicinal and food homologous substances on fasting blood glucose levels

Nine studies [18, 19, 21,22,23, 26,27,28,29] reported the effects of medicinal and food homologous substances, including hawthorn, sea buckthorn, ginger, cardamom, turmeric, cinnamon and puraca, on fasting blood glucose levels. Except for the study of cardamom [22], which found no significant effect on NAFLD, other researches have demonstrated a significant effect on fasting blood glucose levels.

Effects of medicinal and food homologous substances on the levels of liver enzyme AST

Nine studies [18, 19, 21, 23,24,25, 27, 28, 30] reported the effects of medicinal and food homologous substances on AST. These studies included 583 participants, 317 in the intervention group and 266 in the control group. In the two studies involving ginger intervention [21, 24], there was no significant effect on the reduction of AST; in the saffron intervention studies [30], there was no significant effect on the reduction of AST. In the two turmeric studies [25, 27], no significant effect was found on the reduction of AST whether turmeric alone or chicory seed combined. However, in the study [23], turmeric played a significant role in reducing AST. Moreover, hawthorn, sea buckthorn and cinnamon [18, 19, 28] can improve AST levels in patients with NAFLD.

Effects of medicinal and food homologous substances on the levels of liver enzyme ALT

Nine studies [18, 19, 21, 23,24,25, 27, 28, 30] reported the effects of medicinal and food homologous substances on alanine aminotransferase (ALT) levels. These studies included 583 participants, 317 in the intervention group and 266 in the control group. Hawthorn [19], sea buckthorn [18], ginger [21, 24], turmeric [23, 25] and cinnamon [28] all significantly reduced alanine aminotransferase levels. However, another study on turmeric [27] did not find that turmeric intervention significantly improved alanine aminotransferase levels, and saffron [30] did not significantly improve alanine aminotransferase levels.

Summary of results

Due to the high diversity of materials included in the study, this study opted against performing a meta-analysis. The nine medicinal and food homologous substances included can improve the blood lipid levels, blood glucose levels and liver function in patients with NAFLD to a certain extent. However, the impact of turmeric on TC, AST and ALT levels remains a topic of controversy.

Furthermore, this study also summarizes the observations and conclusions included in the research, as shown in Table 3 (In the table file).

Table 3 The observations and conclusions of the included literature
Full size table

Discussion

All 13 articles included in this study were RCTs. The majority of the studies included were evaluated as having some concerns or low-risk bias. Each study compared the subjects' age, sex, education level, levels of blood lipids and glucose, liver function, and other characteristics at the beginning of the study. There was no statistically significant difference in the baseline data (P > 0.05).

In this study, it was found that medicinal and food homologous substances could improve blood lipid and blood glucose levels and liver function in NAFLD patients to a certain extent. Hawthorn, sea buckthorn, ginger, cinnamon, purslane and chicory seeds were able to significantly lower cholesterol. The medicinal and food homologous substances that reduced triglyceride levels were hawthorn, sea buckthorn, cardamom, cinnamon, turmeric and chicory seed. The medicinal and food homologous substances that could improve LDL-C levels were hawthorn, sea buckthorn, ginger, cardamom, turmeric, chicory seed and purslane. The medicinal and food homologous substances that increased HDL-C levels were hawthorn, sea buckthorn, cardamom, turmeric, and chicory seed. Hawthorn, sea buckthorn, ginger, turmeric, cinnamon and purslane were the medicinal and food homologous substances that significantly improved fasting blood glucose levels. Hawthorn, sea buckthorn and cinnamon were the medicinal and food homologous substances that could improve AST levels. Hawthorn, sea buckthorn, ginger and cinnamon were the medicinal and food homologous substances that could improve ALT levels, but the effect of turmeric on TC, AST and ALT levels was controversial. Although saffron does not significantly affect liver enzyme levels, the intervention has a favorable impact on serum levels of inflammation, oxidative stress, and adipokine biomarkers.

Currently, there is a growing trend of systematic evaluations being conducted on medicinal and food homologous substances both domestically and internationally [31,32,33]. However, they are all focused on a single substance and have not been discussed and analyzed from the category of medicinal and food homologous substances. Therefore, this systematic evaluation was carried out. In a meta-analysis examining the effects of sea-buckthorn on factors related to metabolic syndrome [31], it was determined that sea-buckthorn can effectively improve blood lipid levels in individuals with unhealthy lipid profiles, while having no significant impact on those who are already healthy. A systematic review was conducted to investigate the effects of turmeric on liver enzymes in patients with NAFLD [32], the study found that high-dose administration of turmeric can be used as a treatment for NAFLD. This treatment improved liver enzyme levels, and it is believed that it has the best effect within a specific time of supplementation. In addition, a number of animal experiments [34, 35] have also shown that medicinal and food homologous substances can improve lipid metabolism in nonalcoholic fatty liver animal models and have a protective effect on hepatic steatosis, which is consistent with the conclusion of this study. The medicinal and food homologous substances included in this study were hawthorn, sea buckthorn, purslane, turmeric, chicory seed, ginger, saffron, cardamom and cinnamon, but the number of studies on these individual substances was less than 5.

Intervention with medicinal and food homologous substances in patients with NAFLD may potentially benefit them by improving blood glucose, blood lipids, and liver function. However, the extent of these benefits may vary depending on factors such as the type of intervention substance used, timing of intervention, dosage administered, and other related variables. Among the included literature, intervention duration ranged from 8 weeks to 3 months and various types of intervention substances were utilized. In one study [25], a group of participants received joint interventions with two medicinal and food homologous substances. Furthermore, inconsistencies in dosage were observed when the same medicinal and food homologous substances were used across different studies. Moreover, NAFLD is associated with dietary and lifestyle factors. Among the studies included, three [18, 19, 29] incorporated additional interventions such as health education, dietary guidance, and tai chi exercise assistance in conjunction with medicinal and food homologous substance interventions. Ten studies [18, 21,22,23,24,25, 27,28,29,30] evaluated the dietary intake of study participants. These variables have the potential to impact the findings of this investigation.

In China, the use of medicinal and food homologous substances has a long history and is documented extensively in medical classics. In Iran, which is a country also interested in traditional herbal treatments, there are approximately 2,300 different types of medicinal plants with therapeutic value [36]. All studies included in the present research are from China and Iran, which may be related to the local gastronomic and medical traditions. The homologous substances of medicine and food contain rich nonnutrients, which are different from the chemical structure of nutrients. Furthermore, these substances can sustain the physiological processes of the human body and prevent several disorders. By mitigating oxidative stress and reducing inflammation, these substances have the potential to impede the progression of chronic diseases. It is worth noting that adhering to healthy dietary habits over an extended period can significantly enhance human health [37].

For the treatment of chronic diseases, this research group proposed the theoretical model of family nurse diet. In this model, the top represents nonnutrients, the bottom is an equilateral triangle made up of oxidative stress, inflammation, and metabolic problems, and the height is the dietary prescription from the family nurse. The model has been proposed to aid in the management of chronic diseases by means of its anti-inflammatory, antioxidant, and metabolic regulatory properties [37]. The lipid metabolism of patients with NAFLD is disturbed, and transaminase and blood glucose levels are higher than those of the normal population [38]. Basic research [39] found that nonalcoholic fatty liver is closely related to inflammation, oxidative stress and metabolic disorders. Quercetin, curcumin, proanthocyanidins, and other phenolic compounds are significant nonnutrients and are linked to human health. They are among the most abundant nonnutrients found in medicinal and food homologous substances. The majority of edible plants include phenolic acids and flavonoids and display immune enhancing, anti-infective, antioxidative, antiviral, and antibacterial effects [37]. In addition, the flavonoids found in many medicinal and food homologous substances have protective effects against liver damage, can control blood cholesterol levels, can act as anti-inflammatory and anticancer compounds and have a few preventive abilities against diabetes and hyperlipidemia [40, 41]. The abundant flavonoids in hawthorn may have pharmacodynamic effects on processes such as regulating cell growth and survival, lowering lipoprotein lipase levels, and minimizing inflammatory reactions [42]. The flavonoids present in seabuckthorn have the potential to reduce blood viscosity, enhance vascular compliance, augment blood circulation, lower low-density lipoprotein and cholesterol levels, as well as ameliorate serum cholesterol and insulin resistance among patients with NAFLD [43]. Purslane, which is an annual succulent herb, is also an important medicinal and food homologous plant. In animal studies, the total flavonoids extracted from purslane have been shown to mitigate oxidative stress and inflammation, as well as regulate abnormal lipid metabolism in cases of liver injury induced by NAFLD in mice [44]. Curcumin extracted from turmeric has demonstrated remarkable in vivo activities, including potent antioxidant, anti-inflammatory, antifibrotic, antiaging and antitumor effects; these properties may be responsible for the liver-protective properties of turmeric [45]. Moreover, chicory lowers blood fat levels and protects the liver. Additionally, its ingredient chlorogenic acid has an anti-obesity impact and enhances lipid metabolism [46]. The therapeutic benefits of ginger may be attributed to its ability to modulate transcription factors, particularly compounds like 6-gingerol that can regulate the expression of key genes involved in lipid metabolism and inflammation while also suppressing hepatic steatosis [47, 48]. Saffron or crocin can prevent NAFLD-mediated oxidative stress and inflammatory reactions by lowering liver enzyme levels and slowing histological alterations [35]. Cardamom has been demonstrated to possess pharmacological activities that are closely associated with human health, including antioxidant, anti-inflammatory, hypoglycemic, and hepatoprotective effects. Notably, its extract can significantly mitigate liver tissue inflammation and necrosis as well as collagen accumulation and activation of hepatic stellate cells, thereby exerting a beneficial effect on liver protection [49]. Cinnamon polyphenols, extracted from cinnamon bark, have demonstrated the ability to mitigate insulin resistance in adipocytes and liver cells while also regulating intracellular lipid metabolism [50]. This study suggests that the above medicinal and food homologs may assist disease prevention and treatment through anti-inflammation, antioxidative stress and improvement of metabolic disorders by utilizing the nonnutrients rich in them. In a randomized controlled study investigating the effects of omega-3 rich camelina sativa oil intervention in patients with NAFLD [51], it was observed that camelina sativa oil supplementation significantly improved glycemic control, inflammation and oxidative stress biomarkers in NAFLD patients. Another study [52] also demonstrated that dietary supplementation with camelina sativa oil had a positive impact on certain liver enzymes, lipid profiles, and other indicators in patients with NAFLD. This finding further supports the premise of our study. Many clinical studies have not deeply studied the active components of medicinal and food homologous substances, but their liver protection and anti-inflammatory effects make them of great developmental value.

At present, the management of chronic diseases has become the primary task of current health care. Clinical and laboratory investigations have demonstrated that the development of most chronic diseases is intricately linked to oxidative stress, inflammation, and metabolic dysregulation [53, 54], and healthy dietary patterns are effective in disease intervention, guiding the formulation and implementation of tertiary prevention strategies for chronic noncommunicable diseases at the macro level [37]. The dietary regimen based on the concept of food and medicine sharing the same origin can serve as a tertiary prevention strategy for disease prevention and health promotion in the general population, while also playing a positive role in treating and rehabilitating patients with NAFLD. This provides ideas for clinical nondrug intervention and management of the NAFLD population.

Six [21,22,23, 25, 26, 29] of the 13 RCTs included in the present analysis showed no negative effects after using medicinal and food homologous substances. In six studies [18,19,20, 24, 27, 28], no adverse effects were reported. One patient in the intervention group in one of the studies [30] was excluded due to saffron allergy, but no adverse responses were reported in the other investigations. Medicinal and food homologous substances are low-cost supplemental natural drugs that can postpone the development of NAFLD and lessen the side effects and adverse responses associated with conventional drug treatment. Medicinal and food homologous substances are safe and affordable treatment options. The nine medicinal and food homologous substances involved in this study all have certain beneficial effects for patients with NAFLD, providing a basis and guidance for clinical dietary guidance for patients with NAFLD. It is possible to develop personalized dietary adjuvant therapy for patients with NAFLD according to related indicators to prevent the development of the disease and promote the recovery of patients.

Strengths and limitations

The strength of this study lies in the credibility of its findings, which are derived from randomized controlled trials and based on studies of overall good quality. However, this study has some limitations. Firstly, the included studies were limited to China and Iran, which may limit the generalizability of this research findings. Secondly, this research search strategy was restricted to Chinese and English articles only, potentially leading to important studies being overlooked and affecting the overall results. In addition, the technique, dosage, and timing of intervention with medicinal and food homologous substances in the included studies varied, which may have impacted the evaluation of their efficacy; therefore, meta-analysis was not conducted in this study.

Conclusion

The results indicated that the utilization of medicinal and food homologous substances exhibited a significant improvement in serum lipid levels (TC, TGs, LDL-C, and HDL-C), FBG, as well as liver enzymes (ALT and AST) among patients diagnosed with NAFLD. However, the impact of turmeric on TC, AST, and ALT remains a topic of debate. In addition, saffron has been shown to have no significant impact on hepatic enzymes, while exhibiting favorable effects on serum levels of inflammation, oxidative stress, and adipokine biomarkers. This may be related to the intervention time and dose of medicinal and food homologous substances. Medicinal and food homologous substances have fewer side effects and are safer, economical and rich in nonnutrients compared with drugs. This study presents a novel adjuvant therapy regimen and dietary guidance for patients with NAFLD, which plays a pivotal role in the prevention and management of this disease.

Availability of data and materials

The original data involved in the manuscript can be obtained from the references.

Abbreviations

AST:

Aspartate aminotransferase

ALT:

Alanine aminotransferase

FBG:

Fasting blood glucose

HDL-C:

High-density lipoprotein cholesterol

LDL-C:

Low-density lipoprotein cholesterol

NAFLD:

Nonalcoholic fatty liver disease

TC:

Total cholesterol

TGs:

Triglycerides

References

  1. David K, Kowdley KV, Unalp A, Kanwal F, Brunt EM, Schwimmer JB, et al. Quality of life in adults with nonalcoholic fatty liver disease: baseline data from the nonalcoholic steatohepatitis clinical research network. Hepatology. 2009;49(6):1904–12.

    PubMed  Google Scholar 

  2. Allen AM, Therneau TM, Larson JJ, Coward A, Somers VK, Kamath PS. Nonalcoholic fatty liver disease incidence and impact on metabolic burden and death: a 20 year-community study. Hepatology. 2018;67(5):1726–36.

    CAS  PubMed  Google Scholar 

  3. The Lancet Gastroenterology H. Redefining non-alcoholic fatty liver disease: what’s in a name? Lancet Gastroenterol Hepatol. 2020;5(5):419.

    Google Scholar 

  4. Schwenger KJ, Allard JP. Clinical approaches to non-alcoholic fatty liver disease. World J Gastroenterol. 2014;20(7):1712–23.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Nasiri-Ansari N, Kassi E. Editorial: special issue: non-alcoholic fatty liver disease: from molecular basis to therapeutic advances. Metabol Open. 2023;17: 100229.

    PubMed  PubMed Central  Google Scholar 

  6. Zhou ZT, Deng LM, Hu LJ, Ren Q, Zhang LY, Li Z. Recent advances in research on targets and drugs for treatment of nonalcoholic fatty liver disease. Chin New Drug. 2020;29(12):1363–74.

    Google Scholar 

  7. Powell EE, Wong VW, Rinella M. Non-alcoholic fatty liver disease. Lancet. 2021;397(10290):2212–24.

    CAS  PubMed  Google Scholar 

  8. Zhang L, Chen D, Huang MA. An analysis of Li Shizhen’s contribution to the homology of medicine and food. Lishizhen Med Mate Med Res. 2022;33(11):2772–5.

    Google Scholar 

  9. Guo YJ. The therapeutic effect of non-nutrients in food. Chin J Nat Med. 2001;04:218–9.

    Google Scholar 

  10. Ministry of Health of the People's Republic of China. Notice of the Ministry of Health on Further Regulating the Management of Raw Materials of Health Food (Health Law Supervision [2002] No.51. http://www.nhc.gov.cn/zwgk/wtwj/201304/e33435ce0d894051b15490aa3219cdc4.shtml.

  11. Liu HH, Zeng HM, Zhang GC, Sun XS. Analysis ofthe changes of description of food and drug homologous herbs from the perspective of psychical transmutation. China J Tradit Chin Med Pharm. 2022;37(10):6123–6.

    Google Scholar 

  12. Cui G, Bai J, Miao L, et al. Effects of Fructus Lycii on T helper cell 17 and related cytokines in non-alcoholic fatty liver disease. Chin J Clin Pharmacol. 2020;36(3):309–12.

    Google Scholar 

  13. Li H, Pang D, Liu Y, et al. Effects of Cinnamon cassia free phenolic extract on nonalcoholic hepatocyte steatosis. J South Argicult. 2022;53(3):879–90.

    CAS  Google Scholar 

  14. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372: n71.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Yu J. Catalogue of homologous raw materials of medicine and food (Edition). Oral Care Ind. 2017;27(6):24–8.

    Google Scholar 

  16. State Health Commission, State Administration for Market Regulation. Notice on Piloting the material management of nine substances including Codonopsis codonopsis, which are traditionally both food and medicinal herbs (Guowei Food Letter (2019) No.311. http://www.nhc.gov.cn/sps/s7885/202001/1ec2cca04146450d9b14acc2499d854f.shtml.

  17. Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (editors). Cochrane Handbook for Systematic Reviews of Interventions version 6.3 (updated February 2022). Cochrane, 2022. Available from www.training.cochrane.org/handbook.

  18. Liu MY, Wang CY, Zhang X, Zhu RF, Cao Y, Feng YQ, et al. Effect of Tartary buckwheat and sea buckthorn vinegar Drink combined on patients with metabolic-related fatty liver disease [J]. Chin Gen Pract Nurs. 2022;20(7):934–8.

    Google Scholar 

  19. Liu LM. Experimental observation of Taiji soft power ball combined with Hawthorn tea in patients with NAFLD. Chin Commun Doctors. 2012;14(4):272–3.

  20. Tao ZH. Pharmacologic analysis of long-term high dose single Herb Hawthorn on blood lipids in patients with nonalcoholic fatty liver disease caused by high fat diet. Guangming J Chin Med. 2021;36(12):1991–3.

  21. Rafie R, Hosseini SA, Hajiani E, Malehi AS, Mard SA. Effect of ginger powder supplementation in patients with non-alcoholic fatty liver disease: a randomized clinical trial. Clin Exp Gastroenterol. 2020;13:35–45.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Daneshi-Maskooni M, Keshavarz SA, Qorbani M, Mansouri S, Alavian SM, Badri-Fariman M, et al. Green cardamom supplementation improves serum irisin, glucose indices, and lipid profiles in overweight or obese non-alcoholic fatty liver disease patients: a double-blind randomized placebo-controlled clinical trial. Bmc Complement Altern Med. 2019;19:59.

    PubMed  PubMed Central  Google Scholar 

  23. Jarhahzadeh M, Alavinejad P, Farsi F, Husain D, Rezazadeh A. The effect of turmeric on lipid profile, malondialdehyde, liver echogenicity and enzymes among patients with nonalcoholic fatty liver disease: a randomized double blind clinical trial. Diabetol Metab Syndr. 2021;13(1):112.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Rahimlou M, Yari Z, Hekmatdoost A, Alavian SM, Keshavarz SA. Ginger supplementation in nonalcoholic fatty liver disease: A randomized, double-blind, placebo-controlled pilot study. Hepa Monthly. 2016;16(1):e34897.

    Google Scholar 

  25. Ghaffari A, Rafraf M, Navekar R, Sepehri B, Asghari-Jafarabadi M, Ghavami SM. Turmeric and chicory seed have beneficial effects on obesity markers and lipid profile in non-alcoholic fatty liver disease (NAFLD). Int J Vitam Nutr Res. 2019;89(5–6):293–302.

    CAS  PubMed  Google Scholar 

  26. Ghaffari A, Rafraf M, Navekar R, Sepehri B, Asghari-Jafarabadi M, Ghavami SM. Effects of turmeric on homocysteine and Fetuin-A in patients with nonalcoholic fatty liver disease: a randomized double-blind placebo-controlled study. Iran Red Cresc Med J. 2017;19(4):e43193.

  27. Navekar R, Rafraf M, Ghaffari A, Asghari-Jafarabadi M, Khoshbaten M. Turmeric supplementation improves serum glucose indices and leptin levels in patients with nonalcoholic fatty liver diseases. J Am Coll Nutr. 2017;36(4):261–7.

    CAS  PubMed  Google Scholar 

  28. Askari F, Rashidkhani B, Hekmatdoost A. Cinnamon may have therapeutic benefits on lipid profile, liver enzymes, insulin resistance, and high-sensitivity C-reactive protein in nonalcoholic fatty liver disease patients. Nutr Res. 2014;34(2):143–8.

    CAS  PubMed  Google Scholar 

  29. Gheflati A, Adelnia E, Nadjarzadeh A. The clinical effects of purslane (Portulaca oleracea) seeds on metabolic profiles in patients with nonalcoholic fatty liver disease: a randomized controlled clinical trial. Phytother Res. 2019;33(5):1501–9.

    CAS  PubMed  Google Scholar 

  30. Pour FK, Aryaeian N, Mokhtare M, Mirnasrollahi Parsa RS, Jannani L, Agah S, et al. The effect of saffron supplementation on some inflammatory and oxidative markers, leptin, adiponectin, and body composition in patients with nonalcoholic fatty liver disease: A double-blind randomized clinical trial. Phytother Res. 2020;34(12):3367–78.

    CAS  PubMed  Google Scholar 

  31. Geng Y, Wang J, Chen K, Li Q, Ping Z, Xue R, et al. Effects of sea buckthorn (Hippophae rhamnoides L.) on factors related to metabolic syndrome: a systematic review and meta-analysis of randomized controlled trial. Phytother Res. 2022;36(11):4101–14.

    CAS  PubMed  Google Scholar 

  32. Mansour-Ghanaei F, Pourmasoumi M, Hadi A, Joukar F. Efficacy of curcumin/turmeric on liver enzymes in patients with non-alcoholic fatty liver disease: a systematic review of randomized controlled trials. Integr Med Res. 2019;8(1):57–61.

    PubMed  Google Scholar 

  33. Samadi M, Moradinazar M, Khosravy T, Soleimani D, Jahangiri P, Kamari N. A systematic review and meta-analysis of preclinical and clinical studies on the efficacy of ginger for the treatment of fatty liver disease. Phytother Res. 2022;36(3):1182–93.

    CAS  PubMed  Google Scholar 

  34. Li Y, Wang C, Jin Y, Chen H, Cao M, Li W, et al. Huang-Qi San improves glucose and lipid metabolism and exerts protective effects against hepatic steatosis in high fat diet-fed rats. Biomed Pharmacother. 2020;126:109734.

    CAS  PubMed  Google Scholar 

  35. Mashmoul M, Azlan A, Mohtarrudin N, Mohd Yusof BN, Khaza’ai H, Khoo HE, et al. Protective effects of saffron extract and crocin supplementation on fatty liver tissue of high-fat diet-induced obese rats. BMC Complement Altern Med. 2016;16(1):401.

    PubMed  PubMed Central  Google Scholar 

  36. Fang TY. Iranian traditional medicine is widely used. Chinese Health. 2009;10:82–82.

    Google Scholar 

  37. Han SF, Feng YQ, Gao WQ. Theoretical model of non⁃nutrient diet therapy for prevention and treatment of chronic diseases. Chin Nurs Res. 2023;37:565.

    Google Scholar 

  38. Wang YY. Observation of blood lipid, blood glucose and liver function in patients with nonalcoholic fatty liver disease. China Pract Med. 2022;17(01):89–91.

    Google Scholar 

  39. Farzanegi P, Dana A, Ebrahimpoor Z, Asadi M, Azarbayjani MA. Mechanisms of beneficial effects of exercise training on non-alcoholic fatty liver disease (NAFLD): Roles of oxidative stress and inflammation. Eur J Sport Sci. 2019;19(7):994–1003.

    PubMed  Google Scholar 

  40. Xu XJ, Zhang XF, Xu DQ, Chen YM. Research progress in the regulation of blood lipid by flavonoids. China Pharm. 2016;27(01):114–7.

    CAS  Google Scholar 

  41. Guo JJ, Yang XF. Research progress of the protective effect of flavanoids on experimental liver injury of animals. Chin Pharmacol Bull. 2008;01:5–10.

    Google Scholar 

  42. Li H, Gao L, Shao H, Li B, Zhang C, Sheng H, et al. Elucidation of active ingredients and mechanism of action of hawthorn in the prevention and treatment of atherosclerosis. J Food Biochem. 2022;46(12): e14457.

    CAS  PubMed  Google Scholar 

  43. Zhong QW, Wu YY, Xiong F, Liu M, Liu YP, Wang C, et al. Higher flavonoid intake is associated with a lower progression risk of non-alcoholic fatty liver disease in adults: a prospective study. Br J Nutr. 2021;125(4):460–70.

    CAS  PubMed  Google Scholar 

  44. Yao RQ, Song WQ, Hu XL, Zhang WH. The effects of portulaca oleracea total flavones on non-alcoholic fatty liver disease in mice. Curr Immunol. 2021;41(06):448–54.

    Google Scholar 

  45. Hu RW, Carey EJ, Lindor KD, Tabibian JH. Curcumin in hepatobiliary disease: Pharmacotherapeutic properties and emerging potential clinical applications. Ann Hepatol. 2017;16(6):835–41.

    CAS  PubMed  Google Scholar 

  46. Cho AS, Jeon SM, Kim MJ, Yeo J, Seo KI, Choi MS, et al. Chlorogenic acid exhibits anti-obesity property and improves lipid metabolism in high-fat diet-induced-obese mice. Food Chem Toxicol. 2010;48(3):937–43.

    CAS  PubMed  Google Scholar 

  47. Wang J, Ke W, Bao R, Hu X, Chen F. Beneficial effects of ginger Zingiber officinale Roscoe on obesity and metabolic syndrome: a review. Ann N Y Acad Sci. 2017;1398(1):83–98.

    PubMed  Google Scholar 

  48. Tzeng TF, Liou SS, Chang CJ, Liu IM. 6-gingerol protects against nutritional steatohepatitis by regulating key genes related to inflammation and lipid metabolism. Nutrients. 2015;7(2):999–1020.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Xian KF, Yin H. Research progress on chemical constituents and pharmacological activities of Amomum plants. Nat Prod Res Dev. 2019;31(10):1831–6.

    Google Scholar 

  50. Sartorius T, Peter A, Schulz N, Drescher A, Bergheim I, Machann J, et al. Cinnamon extract improves insulin sensitivity in the brain and lowers liver fat in mouse models of obesity. PLoS ONE. 2014;9(3): e92358.

    PubMed  PubMed Central  Google Scholar 

  51. Musazadeh V, Dehghan P, Saleh-Ghadimi S, Farhangi MA. Omega 3-rich Camelina sativa oil in the context of a weight loss program improves glucose homeostasis, inflammation and oxidative stress in patients with NAFLD: A randomised placebo-controlled clinical trial. Int J Clin Pract. 2021;75(11): e14744.

    CAS  PubMed  Google Scholar 

  52. Musazadeh V, Dehghan P, Khoshbaten M. Efficacy of omega-3-rich Camelina sativa on the metabolic and clinical markers in nonalcoholic fatty liver disease: a randomized, controlled trial. Eur J Gastroenterol Hepatol. 2022;34(5):537–45.

    CAS  PubMed  Google Scholar 

  53. Luc K, Schramm-Luc A, Guzik TJ, Mikolajczyk TP. Oxidative stress and inflammatory markers in prediabetes and diabetes. J Physiol Pharmacol. 2019;70(6):809–24.

  54. Steven S, Frenis K, Oelze M, Kalinovic S, Kuntic M, Jimenez MTB, et al. Vascular inflammation and oxidative stress: major triggers for cardiovascular disease. Oxid Med Cell Longev. 2019;2019:7092151.

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

This study was funded by Shanxi Province “136 Revitalization Medical Project Construction Funds” and the Foundation of Evidence-based Nursing of Peking University (XZSR-2022-12).

Author information

Authors and Affiliations

  1. General Surgery Department, Shanxi Bethune Hospital/Third Hospital of Shanxi Medical University, Taiyuan, China

    Qian Zhang & Yatian Jia

  2. School of Nursing/Research Center of Dietary Therapy Technology, Shanxi Medical University, Taiyuan, China

    Qian Zhang & Shifan Han

  3. School of Nursing, Shanxi University of Chinese Medicine, Jinzhong, China

    Yatian Jia, Yuexing Zhang & Xinru Li

  4. School of Nursing, Peking University, Beijing, China

    Yan Wang

  5. Department of Infection and Toxic Liver Diseases, The Third People’s Hospital of Taiyuan, Taiyuan, China

    Xiaoying Tian

  6. First Hospital of Shanxi Medical University, Taiyuan, China

    Shifan Han

Authors
  1. Qian Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yatian Jia
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yuexing Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xinru Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xiaoying Tian
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shifan Han
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

QZ proposed the research topic, while QZ, Yt J, and Yx Z conducted a comprehensive literature search and data extraction to evaluate the risk of bias in the included studies. Data analysis was performed by Yt J and QZ, with manuscript writing completed by Yt J. The manuscript was reviewed and revised by YW, Xy T, Xr L, and Sf H before being approved by all authors.

Corresponding author

Correspondence to Shifan Han.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

The authors unanimously agreed to publish the manuscript. What this study did was not covered by previous studies. This manuscript will not be published elsewhere.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Additional file 1.

The search strategy.

Additional file 2.

PRISMA 2020 Checklist.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, Q., Jia, Y., Zhang, Y. et al. The effects of medicinal and food homologous substances on blood lipid and blood glucose levels and liver function in patients with nonalcoholic fatty liver disease: a systematic review of randomized controlled trials. Lipids Health Dis 22, 137 (2023). https://doi.org/10.1186/s12944-023-01900-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12944-023-01900-5

Keywords

Lipids in Health and Disease

ISSN: 1476-511X