A Scoping Review of the Clinical Evidence for the Health Benefits of Culinary Doses of Herbs and Spices for the Prevention and Treatment of Metabolic Syndrome

Metabolic syndrome (MetS) is a growing global health problem. Evidence suggests that diets rich in phytochemical-containing herbs and spices can contribute to reducing the risk of chronic diseases. This review assesses the scope of evidence supporting the use of herbs and spices in the diet for the prevention or treatment of MetS and its associated health conditions. A search of the PubMed, Scopus and Google Scholar databases was carried out to assess the available clinical evidence for culinary doses of commonly used herbs and spices. Trials that were measuring health factors related to metabolic disorders in healthy individuals, or the health of individuals with MetS or associated diseases, were included. Out of a total of 1738 papers identified, there were 142 relevant studies on black pepper, chilli, cardamom, cinnamon, coriander, cumin, fennel, fenugreek, garlic, ginger, nigella seed, rosemary, sage and turmeric. No relevant research was found for cloves, mint, oregano, parsley or thyme. Cinnamon, fenugreek and ginger were the herbs/spices with the most published trials on them and that showed promise for glycaemic control. Cardamom appears to have potential to reduce inflammatory markers, and cinnamon, ginger and turmeric to reduce blood lipids. Patients with type 2 diabetes were the population most likely to be included in studies, but the preventative benefits of herbs/spices in healthy populations were also investigated, particularly for chilli, ginger and cinnamon. There is evidence for the beneficial effect of culinary doses of many common herbs/spices in the prevention and treatment of MetS and associated disorders.


Introduction
Metabolic syndrome (MetS) and its associated conditions, such as obesity, diabetes and cardiovascular disease, are a growing global health problem.Between 2000 and 2019, global diabetes rates grew by more than 1.5% annually and prevalence rates for all other metabolic diseases also increased [1].Poor diet and physical inactivity are risk factors for the development of MetS and lifestyle changes are key for treatment [2].MetS involves the dysregulation of blood glucose, insulin resistance, raised blood lipids, increased inflammation and high blood pressure [2].Therefore, measuring these biomarkers in healthy individuals can indicate the risk of MetS developing or can be used to monitor progress in those with MetS.
Research indicates that the inclusion of herbs and spices in the diet, as is often the case in Mediterranean and Asian diets, may contribute to positive long-term health outcomes [3,4].Herbs and spices are a particularly rich source of phytochemicals and the consumption of diets rich in phytochemicals has been linked with a reduced risk of cardiometabolic disease and obesity [5,6].
Nutrients 2023, 15, 4867 2 of 44 Many studies looking at the health benefits of herbs and spices use high-dose extracts; however, these do not reflect the main way that the general public might be able to take advantage of these relatively cheap additions to their diet.Are these more expensive high-dose formulations necessary for everyone to benefit from herbs and spices, or do culinary doses provide benefits too?Some researchers have begun to investigate this question.Clinical studies using herb and spice mixes to improve physiological responses to food have indicated that the inclusion of herbs/spices in the diet may have preventative or therapeutic benefits [7][8][9][10][11][12][13][14][15].The spice mixes used in these studies ranged in dose from 6 g to 23.5 g and positively impacted vascular function, blood glucose and insulin and blood lipids following meals.These effects may contribute to a reduced risk of MetS and its associated conditions when herbs and spices are consumed regularly.The reasons for the specific herb/spice mixes chosen and doses used were often not explained.Doses of 6 g of Italian herb mixes [8], 23.5 g of Asian spices [11] or a combination of Mediterranean herbs and Asian spices at doses of 14.5 g [10] and between 0.5 and 6.6 g [13,14] have been found to have benefits.The lack of consistency in herb/spice mix formulations makes it challenging to attribute benefits to a particular herb/spice, a combination of herb/spices or a dose.
Zanzer et al. assessed the effect of the concentrated liquid extracts of individual spices, but standardized them to equal polyphenol contents, enabling the different effects from each spice to be elucidated [15].The dose of polyphenols provided from each extract corresponded to the amount found in 6 g of cinnamon.Cinnamon and turmeric positively impacted on blood sugar levels, and turmeric reduced appetite; however, ginger and star anise did not have any effect.Therefore, the individual effects from different herbs goes beyond a general benefit from polyphenol intake and needs to be clarified.
The purpose of a scoping review is to identify a body of evidence, explore how it has been reported, identify evidence gaps [16], and perhaps to inform the development of future systematic reviews [17].The many different types of evidence available for the health benefits of herbs/spices mean that systematic review methods are not yet appropriate.This methodology uses a systematic approach to searching, but produces qualitative results to highlight available research and provide a base for determining what further research is needed.
Therefore, the aim of this review was to assess the clinical evidence available for the metabolic health benefits of culinary doses of a range of common herbs and spices and to investigate whether there was consistency in the doses used and outcomes found.The most promising herbs and spices in the diet for specific health outcomes or populations can be identified, as well as the future clinical research needed to confirm this effect.

Search Strategy
The PICO (population, intervention, comparison, outcome) strategy was used to formulate search terms.The research question was as follows: do herbs and spices affect symptoms of MetS in healthy or relevant diseased populations?The population was healthy individuals or those with MetS and related disorders.The intervention was single herbs or spices at culinary doses.The comparison was a control or no treatment.The outcome was a change in symptoms associated with MetS or a change in relevant biomarkers: blood glucose, lipids, insulin or inflammatory markers.PubMed and Scopus were searched in January 2023 with no date restrictions applied.A search of PubMed database was carried out using the search terms: ("black pepper" or "Piper nigrum" or "black seed" or "black cumin" or "Nigella sativa" or cardamom or "Elettaria cardamomum" or chilli or "Capsicum frutescens" or cinnamon or "Cinnamomum zeylanicum" or cloves or "Syzygium aromaticum" or coriander or "Coriandrum sativum" or cumin or "Cuminum cyminum" or fennel or "Foeniculum vulgare" or fenugreek or "Trigonella foenum-graecum" or garlic or "Allium sativum" or ginger or "Zingiber officinale" or mint or "Mentha" or oregano or "Origanum vulgare" or parsley or "Petroselinum crispum" or rosemary or "Rosmarinus officinalis" or sage or "Salvia officinalis" or thyme or "Thymus vulgaris" or turmeric or "Curcuma longa") AND (metabol* or diabetes or obesity or cardiovascular or "blood glucose" or "blood sugar" or "blood lipids" or "blood fats" or "blood insulin").The results were filtered by Clinical Trial as the article type.Each herb/spice was searched for separately in Scopus, with the following search term: TITLE-ABS-KEY ({herb/spice name}) AND TITLE-ABS-KEY (metabolic OR metabolism OR diabetes OR obesity OR cardiovascular) AND TITLE (clinical OR human).Additional studies were found using Google Scholar and hand searching reference lists from relevant reviews.

Inclusion and Exclusion Criteria
The inclusion criteria were the use of a whole herb/spice or powdered/ground herb/spice in food, drinks or encapsulated and at doses that could reasonably be achieved in the diet without negatively impacting palatability.Concentrated extracts or oils and combinations of herbs or spices were excluded.Studies of water infusions or herbal teas were included when the formulation and quantity was what might be reasonably consumed at home.Any studies that administered herbal formulations or more than one herb/spice at a time were excluded; however, those with multiple individual herbs/spices being investigated in separate arms of the study were included.To ensure a broad range of different studies, clinical trials that were measuring biomarkers related to metabolic disorder in healthy individuals or the health of individuals with metabolic disease or related conditions were included.Studies were included regardless of the age or health status of participants, as the intention was to determine the potential for herbs and spices to both prevent and treat metabolic disease.However, if the participants had a co-morbidity not related to MetS the study was excluded.Studies were included regardless of language.Any retrieved studies not in English were translated using Google Translate.Animal and in vitro studies were excluded.Reviews were excluded.

Study Selection and Data Collection
The articles identified from title and abstract screening were added into a Microsoft Excel spreadsheet, the papers were retrieved, and final inclusion decisions were made by reading the full text.Two reviewers (MM and VR) screened this list to decide on the final included studies.For each article, the following data were entered into the spreadsheet: study type, herb/spice investigated, population, dose of herb/spice, length of study and outcome measures.The evidence for each herb/spice was clustered into type of metabolic health measurement investigated, and whether there were positive findings or not.The Jadad Scale was used to score the methodological quality of the clinical trials.The Jadad scale was originally developed for assessing clinical trials in pain research, but has been widely adapted and is considered to offer the best validity and reliability evidence [26].It has limitations in trials investigating food, due to the difficulty in blinding with fresh food, but was still considered the most appropriate.One point is scored for each of the following: a mention of randomisation; a description of an appropriate randomisation method; a mention of blinding; a description of an appropriate blinding method; and, all participants in the trial being accounted for in the results.Trials that scored 0-2 were considered low quality and those scoring 3-5 were considered high quality.

Results
The PubMed search identified 792 results, while the Scopus search produced 925 results.An additional 21 papers were found from Google Scholar and reference list scanning.Title and abstract screening led to 254 papers for full-text screening.This led to a total of 142 relevant papers for data extraction (Figure 1).widely adapted and is considered to offer the best validity and reliability evidence [26].It has limitations in trials investigating food, due to the difficulty in blinding with fresh food, but was still considered the most appropriate.One point is scored for each of the following: a mention of randomisation; a description of an appropriate randomisation method; a mention of blinding; a description of an appropriate blinding method; and, all participants in the trial being accounted for in the results.Trials that scored 0-2 were considered low quality and those scoring 3-5 were considered high quality.

Results
The PubMed search identified 792 results, while the Scopus search produced 925 results.An additional 21 papers were found from Google Scholar and reference list scanning.Title and abstract screening led to 254 papers for full-text screening.This led to a total of 142 relevant papers for data extraction (Figure 1).Evidence was found for black pepper, chilli, cardamom, cinnamon, cloves, coriander, cumin, fennel, fenugreek, garlic, ginger, nigella seed, rosemary, sage and turmeric.No relevant research was found for mint, oregano, parsley or thyme.Table 1 summarises the included studies.The rationale behind the studies excluded at full-text screening is shown in Supplementary Table S1.

Black Pepper, Cardamom and Chilli
There was one single-blind cross-over trial on black pepper in healthy adults.A dose of 1.3 g added to a meal had no impact on appetite or thermogenesis [138].
Ten studies (eight double-blind RCTs, one single-blind RCT and one clinical study) looked at the impact of cardamom on inflammation and a range of metabolic markers in individuals with hypertension [27], diabetes [29,32,59], prediabetes [28], poly-cystic ovarian syndrome (PCOS) [34,35] and non-alcoholic fatty liver disease (NAFLD) [30,33].All the studies on cardamom used 3 g/day for between 8 and 20 weeks.Five out of six studies that investigated inflammatory markers found positive effects [28,[30][31][32]34,35], two studies found benefits on blood glucose and insulin and two studies found no benefit from cardamom on blood lipids, while effects on blood pressure were variable.
Appetite and/or thermogenesis or metabolic rate were measured in eight out of thirteen of the studies and five of these found a beneficial effect.There were as many studies finding positive results as those showing no effect for the key metabolic biomarkers of blood glucose, insulin and lipids (see Figure 2).One cross-over study found an improvement in diet-induced thermogenesis [36] one single-blind cross-over study found increased metabolic rate [44] and one single-blind cross-over study found decreased appetite from chilli [45]; however, four studies found no effect on metabolic rate or energy intake [9,[39][40][41].A reduction in insulin was found in three studies [9,38,42], while an increase was found in one [43].There was no change in blood glucose levels from two randomized cross-over studies [37,39], while one doubleblind RCT [42] and one clinical study [43] found significant reduction in glucose from chilli consumption.The quality of the clinical studies was generally low (8 low and 3 high according to Jadad scores), mainly due to the difficulty in blinding the consumption of chilli in food.

Coriander Seed, Cumin and Fennel
One single-blind RCT found that 2 g/day of coriander seeds for 40 days improved average body mass index (BMI) from 27.3 to 26.7 and blood lipids (total cholesterol, lowdensity lipoprotein (LDL) and high-density lipoprotein (HDL)), as well as systolic blood pressure, in patients with hyperlipidaemia [116].
Two clinical studies looked at the benefit of cumin on anthropometric measures, blood insulin and blood lipid levels in overweight adults [85] and women with dyslipidaemia [86].The randomised clinical trial by Zare et al. used a dose of 6 g/day for 3 months and this reduced all blood lipid measurements, as well as anthropometric measurements of weight, body mass index (BMI), waist circumference and fat [85], while Pishdad et al. used 3 g/day for 8 weeks in a double-blind RCT and found a benefit on total cholesterol, but not LDL or HDL cholesterol [86].
One single-blind crossover study found that a single dose of 2 g of fennel as a tea decreased appetite in healthy women, but did not impact food consumption [87].

Fenugreek
There were twenty studies looking at fenugreek, mainly for its impact on blood glucose, insulin and lipids, in healthy individuals [87,91,92,95], diabetics [89,90,93,94,[96][97][98][99][100][101][103][104][105][106], individuals with coronary artery disease [137] and adults with hyperlipidaemia/hypercholesterolaemia [88,102].Quantities ranged from 2 g up to 100 g, with the majority of studies using 10-15 g/day.Effects on blood insulin, glucose and lipids were promising, with 11 out of 14 studies showing significant positive effects on blood glucose, 7 out of 8 studies finding significant changes in insulin and 6 out of 8 studies significantly improving blood lipids, regardless of dose used.However, excluding low-quality studies reduced the number of studies indicating a benefit on blood glucose (to 4 out of 5 studies) and blood lipid levels (to 1 out of 2 studies).

Garlic
There were ten clinical studies (four double-blind RCTs and six single-blind or randomised clinical studies) looking at the benefits of garlic.Both clinical trials that looked at the effect of garlic on blood pressure (BP) found benefits when participants consumed 20 g or 100 mg/kg bodyweight of fresh garlic daily [107,111].Most of the studies investigated the impact of garlic on blood lipids.One clinical study was carried out on overweight smokers [112].Four clinical studies looked at platelet function [110], cholesterol [108,109], immunity and cancer markers [168] in healthy individuals.Two studies looked at multiple outcomes in patients with MetS [107,115], one study investigated NAFLD [114] and two studies looked at individuals with hyperlipidaemia [111,116].For the interventional studies, doses ranged from 1.6 g to 40 g, with higher doses of fresh garlic compared with dried garlic powder.All but two of the clinical studies looked at blood lipids and seven out of eight found a benefit.Fresh garlic in doses of 100 mg/kg body weight, 20 g or 40 g/day significantly reduced triglycerides in three studies [107,108,111], while two studies found that 1.6 g/day of dried garlic reduced triglycerides [113,115].Total cholesterol was significantly reduced by 1.6, 2 or 3 g/day dried garlic and 20 g or 40 g of fresh garlic [108,109,111,113,116].Only one study of overweight participants at risk of cardiovascular disease found no impact of 2.1 g of garlic on blood lipids [112].

Ginger
Out of a total of 24 studies on ginger, 6 were carried out on healthy individuals to look at blood clotting [119], energy intake and appetite [138], thermoregulatory function or thermogenesis and appetite [118,120], anthropometric measurements [128,133], anthropometric measurements and blood glucose and fats [130] and cardiovascular risk factors [137].There were 11 studies on patients with type 2 diabetes looking at the impact of ginger on blood sugar, insulin and blood lipids [126,134,135], metabolic health and inflammation [125,132], fasting blood glucose and insulin sensitivity [127,129], blood glucose, insulin and inflammation [121], vascular function [122], anthropometric measurements and blood pressure [84] and anthropometric measurements and inflammation [124].One study looked at the effects of 1.5 g of ginger on anthropometric measurements and insulin resistance in women with PCOS [83].One study looked at the effect of 3 g/day on blood lipids in individuals with hyperlipidaemia [136].Two studies looked at the impact of ginger on liver function, anthropometric measurements, blood sugar and inflammatory markers in individuals with NAFLD [117,123].One looked at the impact of 1 g of ginger daily in obese children with NAFLD [117], while, in the other study, adults were given 1.5 g/day [123].A pilot study investigated the impact of 1 g/day of ginger on thyroid symptom score, anthropometric measurements, blood glucose and blood lipids in hypothyroid patients [131].
Ginger was used in doses that ranged from 1 g to 10 g of dried powdered ginger for a single dose or up to 12 weeks daily, apart from one study that used 15 g of fresh ginger or 40 g of cooked ginger [119] and another study that used 20 g of fresh ginger [138].There did not appear to be a correlation between dose and efficacy.All seven studies that investigated the impact of ginger (doses of 1.5-3 g/day) on insulin found a benefit, ten out of twelve found positive effects on blood glucose (doses of 1.2-3 g/day), six out of seven found a positive effect on blood lipids, such as total cholesterol, LDL and triglycerides (doses of 1-3 g) and four out of five studies looking at inflammatory markers (doses of 1.5-3 g) found a benefit.The studies were mainly of high quality (22 out of 24) according to Jadad scoring, with 18 double-blind RCTs, 3 randomized cross-over studies and 3 placebo-controlled study.

Nigella Seeds
There were 17 studies on nigella seeds, mainly investigating their effect on anthropometric measurements, blood glucose, insulin and lipids.One double-blind RCT was carried out on healthy male volunteers [141].A large double-blind RCT looked at the impact of 1.5 g/day of nigella seeds in 250 healthy men with MetS [165].One double-blind RCT was carried out on men with obesity [153].Two studies were carried out with thyroiditis patients [147,150], four in individuals with MetS [139,140,143,152], three in patients with hyperlipidemia/hypercholesterolaemia [144,146,154], three in patients with type 2 diabetes [142,145,151] and two in patients with NAFLD [148,149].The studies on nigella seeds used between 500 mg and 3 g/day for durations ranging from 4 weeks to 1 year.
Nigella seeds improved anthropometric measurements such as BMI and weight in three out of seven studies (at doses of 2-3 g/day), improved blood glucose in five out of ten studies (at doses of 500 mg-2 g/day), insulin (at 2 g/day) in three out of four studies, blood lipids in seven out of eleven studies (at 500 mg-2 g/day) and inflammatory markers in one out of four studies (at a dose of 2 g/day).Of the 17 studies, 13 were high-quality according to Jadad.

Rosemary, Sage and Turmeric
The one high-quality, double-blind RCT on rosemary found no impact on liver enzymes, anthropometric measurements, fasting blood glucose, insulin and blood lipids from 4 g/day for 8 weeks in patients with NAFLD [155].
One low-quality, non-randomised cross-over study found that drinking 600 mL of sage tea daily for 4 weeks improved lipid profile but had no effect on blood glucose in healthy female volunteers aged 40-50 years [156].
Five out of the eleven studies on turmeric looked at patients with type 2 diabetes [157,159,161,162,164].One turmeric study was carried out on healthy volunteers to investigate glycaemic effect [158].Two other studies were carried out on individuals who were stated to be overweight, obese or prediabetic, with no other health issues [166,167].Two studies looked at the effect of turmeric on NAFLD [163,169].The studies used between 1 and 3 g/day for between 4 and 12 weeks, or single doses of 1 g [166] and 6 g [158].
All studies were of a high quality according to Jadad.Three out of five studies investigating anthropometric measurements, such as weight and BMI, found some positive effect from turmeric (at a dose of 2.1 g/day).Four out of seven studies found improvements in blood glucose levels (at doses of 2.1-2 g/day), one out of two studies found improvements in insulin (from a dose of 2 g/day) and five out of six studies found improvements in blood lipids such as triglycerides, total cholesterol and LDL (at doses of 2.1-2.4 g/day).Out of three studies looking at inflammatory markers, two found beneficial effects from 2.1 to 2.4 g/day of turmeric powder in capsules.

Herb/Spice Efficacy
Figure 2 identifies the main health markers measured and whether effects were seen for each of the herbs and spices in all studies and only in high-quality studies.Blood glucose and insulin were the most commonly measured markers, followed by blood lipids, then inflammatory markers.Only including high-quality studies did not make a big difference to the pattern of responses seen for glucose, insulin or inflammatory markers.However, the benefits of fenugreek and garlic on blood lipids were not apparent when only high-quality studies were considered.

Adverse Effects
No adverse effects were reported for any of the studies at the doses used.

Study Quality
Studies were scored for quality using Jadad (details on the scores given are provided in Supplementary Table S2).There were 40 low-quality studies (28% of the scored studies), 97 high quality studies (66% of the scored studies), and 4 studies for which there was not enough information to score them.Of the 142 studies, 81 were double-blind RCTs, 30 were cross-over clinical studies, 30 were single-blind or parallel clinical studies and 1 was a cross-sectional observational study.

Discussion
The aim of this scoping review was to assess the clinical evidence available for culinary doses of herbs and spices, what doses are used and in which health conditions, with a view to identifying areas that need further research.In this review, there were a total of 142 studies looking at the effects of black pepper, chilli, cardamom, cinnamon, cloves, coriander, cumin, fennel, fenugreek, garlic, ginger, nigella seed, rosemary, sage and turmeric on metabolic health.Cinnamon, fenugreek and ginger showed the most promise in controlling blood glucose and insulin.Cinnamon, ginger, nigella seed and turmeric were most promising in terms of having beneficial effects on blood lipid levels.Cardamom, ginger and turmeric showed promise for reducing systemic inflammation due to a decrease in inflammatory markers.Some herbs/spices were more likely to be researched in a specific population or in an investigation of a specific metabolic biomarker.This either indicates increased efficacy or traditional associations and observations stimulating more research in these areas.Findings from in vitro studies or in vivo animal research may also have prompted researchers to focus on a particular herb and effect.For example, despite not having a traditional association with inflammation, the anti-inflammatory effects of cardamom have been found in an animal model [160].
Cardamom was only investigated in individuals with disease associated with MetS and no studies were carried out in healthy individuals.Most studies investigated the impact of cardamom on inflammatory markers.MetS involves increased inflammation; therefore, changes in inflammatory markers are more likely to be observed in those with MetS than healthy individuals.Preclinical research has identified the potential of cardamom for use in inflammation and hyperlipidaemia.Cardamom reduced swelling and downregulated inflammatory cytokines such as cyclo-oxygenase-2 (COX-2) in an animal model [160].This confirms the finding in this scoping review that cardamom has anti-inflammatory activity.A terpenoid compound from cardamom, 1,8-cineole, prevented lipid oxidation in vitro and lowered serum lipid levels in zebrafish, while cardamom oil at a dose of 3 g/kg reduced total cholesterol, LDL-cholesterol and triglycerides in Wistar rats [170].This scoping review did not identify any clinical studies showing a beneficial effect of cardamom on blood lipids, which may reflect a failure of animal studies to relate to effects in humans, or may be due to the difference in dose or formulation.
Almost all the studies on chilli were carried out in healthy individuals.Chilli did not have marked effects on the main insulin, glucose, lipids and inflammatory biomarkers, which may reflect the use of healthy populations for most studies, the doses used or difficulty in blinding chilli consumption in food.It showed more promise for impacting thermogenesis, metabolic rate and appetite.The key active compound in chilli is capsaicin and this binds to transient receptor potential vanilloid receptor 1 (TRPV1) to activate metabolic modulators such as peroxisome proliferator activated receptor (PPAR)α and glucagon-like peptide (GLP)1 [171].Capsaicin has also been found to decrease ghrelin secretion [171], which would explain its appetite-suppressing effects.
The majority of studies on cinnamon were carried out in patients with diabetes, indicating the strong association of this spice with blood sugar control, e.g., references [172][173][174].This impact on blood sugar is thought to be due to an insulin-mimetic effect and via the inhibition of digestive enzymes, such as α-amylase, in the gastrointestinal tract [172,174].Cinnamon activates both PPARα and PPARγ, which would explain its effect on glycaemia [175].However, there was considerable heterogeneity in the effect of cinnamon on blood sugar and blood insulin across the different studies in this review.Cinnamon was more likely to positively impact blood sugar and insulin in healthy individuals than those with type 2 diabetes.Seven out of nine studies (77%) looking at the impact of cinnamon on blood sugar in healthy individuals found a benefit, while only seven out of fifteen studies (47%) looking at the impact of cinnamon on blood sugar in diabetic patients found a benefit.This suggests that it could be of preventative and therapeutic benefit; however, due to the heterogeneity of the results, systematic reviews isolating the impact of the dose and the health of the participants on outcomes would be interesting.There are a number of meta-analyses of cinnamon in diabetes [172,[176][177][178][179][180][181][182]; however, there did not appear to be any assessing blood glucose control in healthy individuals.
The effects of cinnamon on blood sugar, insulin and lipids appeared to be quite mixed from both this scoping review and published meta-analyses.Well-researched areas, such as is found with cinnamon, often highlight heterogenous results.This indicates that further research is needed to separate out the factors that impact efficacy, such as dose, presence in a food matrix, population or duration of study.Yu et al. found that dosage did impact efficacy, with a dose of less than 1.2 g significantly reducing fasting blood glucose, when pooled results found no benefit [175].There have been at least eight meta-analyses of clinical trials of cinnamon looking at LDL-cholesterol.Six found decreases in LDLcholesterol [175,176,180,[183][184][185], but two found no impact on LDL-cholesterol [186,187].Yu et al. found that the effect of cinnamon on LDL-C was influenced by dose [175], which may explain some of the heterogeneity.
Fennel has been used traditionally for its digestive properties [188], but it has also been found to have anti-inflammatory and antihyperlipidaemic activity [20].Bae et al. found that fennel did not impact food consumption; however, it did reduce appetite, indicating that further research might be beneficial [87].
The impact of fenugreek was investigated in patients with diabetes in 14 studies and in healthy individuals in 6 studies.The effects on blood glucose and insulin were mainly positive whether in a healthy or diseased population; however, high-quality studies were less likely to find benefits.Larger doses of fenugreek tended to be used, as the beneficial effect was usually considered to be from the soluble fibre in the seeds [189], although some studies suggest an effect of other compounds such as flavonoids, saponins and the alkaloid trigonelline [190,191].As a relatively mild-flavoured spice, larger amounts are palatable in the diet.The studies using larger quantities incorporated the seed powder into a food matrix, such as being baked into bread; therefore, these were considered culinary doses and were included.
Nine meta-analyses on fenugreek in MetS or associated conditions have been published in the last ten years [189][190][191][192][193][194][195][196][197].All of those that assessed effects on blood glucose found a benefit, but concerns were raised about the quality of the clinical trials.A review of fenugreek in blood pressure found a dose-dependent effect, with doses greater than 15 g/day for longer than 12 weeks being effective [192].Neelakantan et al. also found that dose impacted the effect of fenugreek on glycaemia, with doses higher than 5 g being effective [189].
Studies on garlic looked almost exclusively at blood lipid levels, whether in healthy populations or those with metabolic disorders.Garlic has a strong association with cardiovascular health and cholesterol levels [198][199][200]; however, much of the published research has looked at the effect of standardised garlic extracts, rather than its consumption in food.Systematic reviews and umbrella reviews have identified strong potential for garlic in hyperlipidaemia, hypertension and inflammation [198][199][200].
This review has confirmed the benefits of garlic for hyperlipidaemia and indicates that concentrated extracts may not be necessary in order to benefit from some of the positive health effects from garlic, as both lower and higher doses showed efficacy.There was no relationship between dose and size of effect; for example, the reductions in total cholesterol from 2, 20 and 40 g of garlic compared with control were 82, 19 and 51 mg/dL, respectively [108,111,116].Both low-and high-quality studies, according to Jadad score, showed effectiveness.Garlic and its phytochemicals have been found to have anti-hyperlipidaemic activity via 3-hydroxy-3-methylglutaryl CoA (HMG CoA) inhibition and reduction in cholesterol synthesis; hypotensive activity via angiotensin-converting enzyme (ACE) inhibition, the downregulation of angiotensin II and the stimulation of nitric oxide; and anti-inflammatory/anti-atherosclerotic effects via COX inhibition, the decreased synthesis of thromboxane B2, the decreased production of leukotriene C4 and a reduction in LDL oxidation [201].There are feasible mechanisms of action for the findings and evidence for the benefits of garlic is building.
Most of the ginger studies in healthy populations looked at thermoregulatory function and appetite rather than metabolic biomarkers of glucose, insulin or lipids.The obvious sensorial heating effects on the body from ginger can explain this choice of research.The activation of TRPV1 by pungent principles in spices such as ginger leads to a sensation of heat in the mouth upon consumption and has been suggested to have a thermogenic effect [202].Studies in diabetic patients appeared largely positive for blood glucose, insulin and lipid levels.Whether this is via the activation of TRPV1 receptors, via anti-inflammatory effects through the inhibition of COX and lipoxygenase or via another mechanism remains to be investigated.
Both nigella seeds and turmeric were investigated in a range of health conditions, with no predominance of either healthy individuals or those with type 2 diabetes.This reflects the broad range of uses of these herbs/spices in traditional medicine.
The studies on nigella seeds were heterogenous in terms of the populations investigated and effects seen.The health effects are broad and many traditional medicine systems consider it to be a panacea [203][204][205], which has led to a lack of focus for research into its benefits.However, the phytochemical thymoquinone, found in the essential oil of the seed, has been identified as being responsible for some of the health benefits [203].This may indicate there is likely to be more benefit from the use of nigella seed oil than the seeds.A meta-analysis by Daryabeygi-Khotbehsara et al. found that there was a reduction in triglycerides by nigella seed oil, but not the seeds [206].Sahebkar et al. found that nigella seed powder was more effective than the oil for reducing blood pressure [207], while Askari et al. found that the oil was more effective than the powder for blood glucose control [208].It is likely that thymoquinone and other terpenoids are responsible for supporting healthy blood lipid and glucose levels, but other phytochemicals not found in the oil are responsible for the hypotensive effect.This indicates the importance of assessing the effect of culinary uses separately from that of concentrated food supplements or extracts.Future research focusing on whether dose and formulation impact on the effects and efficacy would be of interest.
There are at least 10 meta-analyses on the use of nigella seeds for MetS and associated conditions [206][207][208][209][210][211][212][213][214][215].These all find benefits of nigella seeds on anthropometric measurements such as body weight, blood lipids, glucose control and inflammation, apart from a review of studies on patients with NAFLD, which found mixed results on blood lipids, inflammatory markers and glucose control [214].
Most studies on turmeric found a beneficial effect, with the most promising areas being inflammation and blood lipids.A meta-review on the health benefits of turmeric by Rolfe et al. identified osteoarthritis and MetS to be the most promising areas of research [216].Turmeric is well researched for its use in inflammatory conditions such as osteoarthritis; however, most research focuses on high-dose curcumin extracts due to the poor bioavailability of curcumin [217].Therefore, it is interesting that the relatively low doses of 2 g were found to have some effect in this review.Sahebkar found in a meta-analysis that overall turmeric reduced CRP, but that bioavailability-improved preparations of curcuminoids were superior [218], so it may be that higher doses are preferable but not essential.
Nearly all of the spices investigated, but none of the herbs, had some evidence to support their use in culinary doses for the prevention or treatment of MetS and associated disorders.Four mixed herb/spice intervention studies found metabolic benefits from Italian herb seasoning mixes or mixes containing Mediterranean herbs rosemary, basil, thyme, oregano and parsley [8,10,13,14]; however, this scoping review has found a lack of studies to confirm the effects of individual herbs mint, parsley, thyme, rosemary, sage and oregano.These plants are particularly rich sources of volatile oils; therefore, research investigating the antimicrobial properties of the essential oil is abundant, e.g., references [219,220].In vitro antimicrobial research is relatively easy to carry out, which may explain why other properties of these herbs have not been investigated to date.In addition to volatile oils, as is the case with the spices cinnamon, turmeric and ginger, these herbs are also good sources of polyphenols [24].Further research into the general health benefits of adding these herbs to the diet would be beneficial.
Considering the widespread use of black pepper in food, it was surprising that there was only one study investigating the impact of this popular condiment for health.It may be that flavour prevents the use of large enough quantities in food for this spice to be of benefit.One study of black pepper was excluded as it investigated the use of a water extract made from 20 g of black pepper, which was not representative of culinary use [15].It was not clear from the methodology what final dose was consumed.However, if it was a comparable dose to that used by Gregersen et al. [138], then the two studies found opposite effects on appetite, with Zanzer et al. finding an effect of black pepper on appetite, but Gregersen et al. finding none.Black pepper contains piperine, which is recognised as a phytochemical that enhances the absorption of other food components [221], as well as some prescription drugs [222].The benefits of black pepper could be largely due to its ability to improve the bioavailability of polyphenols and other phytochemicals in herb/spice mixtures.
Changes in insulin, blood sugar and blood lipids were the most common biomarkers to be investigated.Effective glycaemic control, whether via eating foods with a low glycaemic index or adding in herbs/spices and other phytochemical-containing plant foods that help to reduce the glycaemic index of foods, is crucial for the management and prevention of diabetes, as well as the reduction in cardiometabolic risk factors in diabetics [223].In terms of coronary heart disease risk, only LDL cholesterol has been proven in formal clinical trials to be a biomarker that can be considered a causative factor.Other factors, such as HDL cholesterol, triacylglycerol, vascular function and oxidative damage, require further evidence before their measurement can be considered predictive [224].This scoping review found promise for cardamom, cinnamon, fenugreek, garlic, ginger, nigella seeds and turmeric, as there were positive findings from at least five different studies for one or more of these biomarkers.However, whether this translates to clinically significant effects for patients with MetS remains to be tested.

Limitations and Future Directions
Heterogeneity in the methodology is a major limiting factor in both interpreting the results of this scoping review and the many systematic reviews that have been carried out in this area.As herbs/spices are complex in terms of phytochemistry, as well as effect, and there are not commonly accepted doses, comparisons across different studies are challenging.
The doses used in different studies varied more greatly for herbs/spices which can be used both fresh and dried, such as ginger, garlic and chilli.The difficulty in comparing fresh with dried herbs/spices could be overcome in the future by ensuring that a phytochemical analysis of fresh versus dried samples is carried out.Methodologies that account for differences such as these will add value and enable the clearer comparison of one study with another.Most dried herbs/spices were used in doses of between 1 and 6 g, which is representative of the amounts usually used in cooking (however, the doses were usually chosen based on what amounts had been found to be beneficial in previous studies).A notable exception was fenugreek, which was used in higher doses for the additional fibre benefits.It is possible that investigating higher doses of other herbs/spices may also indicate greater benefit, but this would have to be weighed against palatability.
The combination of multiple herbs and spices is likely to have greater beneficial effect than any individual herb or spice, due to the greater quantity and variety of phytochemicals.A limitation of this scoping review is that focusing on individual herbs prevents comparisons being made with the efficacy of herb/spice mixes.Future research could compare the impact of adding a single herb/spice with that from the synergy of a mix of herbs and spices in the diet, providing a rich variety of phytochemicals.
The duration of the clinical trials is also likely to be a major limiting factor in determining whether consuming herbs and spices in the diet is likely to have a noticeable effect on MetS and cardiovascular health.Although the duration of the studies included in this review did not appear to impact on whether the effect was positive or not, any dietary intervention for preventative health needs to be assessed over a longer period, which adds considerable cost and complexity to trials.Many of these diseases develop over a long period of time, so the next step should be to measure changes in biomarkers associated with them over longer periods.Identifying metabolite markers that indicate an increased consumption of specific herbs may be of use, as has been suggested for measuring the intake of polyphenol-rich foods [225].
The health benefits of herbs/spices are likely due to their phytochemical content and complex interactions between these molecules, other dietary components, the microbiome and the gut wall.Phytochemicals, and polyphenols specifically, have been found to impact carbohydrate absorption and metabolism, gut bacteria populations and the uptake of glucose into muscle and adipose tissue [226].None of the studies incorporated an analysis of the phytochemical content of the herbs/spices used, which would have been a useful addition to tease out the mechanisms or to ascertain which bioactive phytochemicals are driving the effects.The impact of any dietary intervention is dependent on multiple other factors, such as the rest of the diet, participants' stress levels and physical activity; therefore, teasing out the true impact of individual herbs/spices remains a challenge.

Conclusions
Overall, this scoping review has highlighted that there is evidence for the beneficial effect of culinary doses of cardamom, cinnamon, chilli, fenugreek, garlic, ginger, nigella seeds and turmeric in the prevention and treatment of MetS and its associated disorders.Cardamom, ginger and turmeric appear to have the most potential for inflammation linked to MetS, garlic, ginger and turmeric for blood lipids and cinnamon, ginger and fenugreek for blood glucose control.Future research needs to address which factors are most important to unlocking these benefits: the food matrix; the combinations of different herbs/spices; the duration of consumption; and how herb/spice intake interacts with other important dietary and lifestyle changes.

Figure 1 .
Figure 1.PRISMA flow diagram of the screening process.* The number of studies for all the individual herbs has a total sum of more than 145, as some studies included more than one herb in each arm of the study.

Figure 1 .
Figure 1.PRISMA flow diagram of the screening process.* The number of studies for all the individual herbs has a total sum of more than 145, as some studies included more than one herb in each arm of the study.

Figure 2 .
Figure 2. Number of studies and high-quality studies demonstrating the effect of herbs/spices in specific cardiometabolic biomarkers.Figure 2 identifies the main health markers measured and whether effects were seen for each of the herbs and spices in all studies and only in high-quality studies: (a) Number of studies showing an effect or lack of effect for each of the herbs and spices on blood glucose; (b) Number of high-quality studies showing an effect or lack of effect for each of the herbs and spices on blood glucose; (c) Number of studies showing an effect or lack of effect for each of the herbs and spices on insulin; (d) Number of high-quality studies showing an effect or lack of effect for each of the herbs and spices on insulin; (e) Number of studies showing an effect or lack of effect for each of the herbs and spices on blood lipids; (f) Number of high-quality studies showing an effect or lack of effect for each of the herbs and spices on blood lipids; (g) Number of studies

Figure 2
Figure 2. Number of studies and high-quality studies demonstrating the effect of herbs/spices in specific cardiometabolic biomarkers.Figure 2 identifies the main health markers measured and whether effects were seen for each of the herbs and spices in all studies and only in high-quality studies: (a) Number of studies showing an effect or lack of effect for each of the herbs and spices on blood glucose; (b) Number of high-quality studies showing an effect or lack of effect for each of the herbs and spices on blood glucose; (c) Number of studies showing an effect or lack of effect for each of the herbs and spices on insulin; (d) Number of high-quality studies showing an effect or lack of effect for each of the herbs and spices on insulin; (e) Number of studies showing an effect or lack of effect for each of the herbs and spices on blood lipids; (f) Number of high-quality studies showing an effect or lack of effect for each of the herbs and spices on blood lipids; (g) Number of studies

Figure 2 .
Figure 2. Number of studies and high-quality studies demonstrating the effect of herbs/spices in specific cardiometabolic biomarkers.Figure 2 identifies the main health markers measured and whether effects were seen for each of the herbs and spices in all studies and only in high-quality studies: (a) Number of studies showing an effect or lack of effect for each of the herbs and spices on blood glucose; (b) Number of high-quality studies showing an effect or lack of effect for each of the herbs and spices on blood glucose; (c) Number of studies showing an effect or lack of effect for each of the herbs and spices on insulin; (d) Number of high-quality studies showing an effect or lack of effect for each of the herbs and spices on insulin; (e) Number of studies showing an effect or lack of effect for each of the herbs and spices on blood lipids; (f) Number of high-quality studies showing an effect or lack of effect for each of the herbs and spices on blood lipids; (g) Number of studies showing an effect or lack of effect for each of the herbs and spices on inflammatory markers; (h) Number of high-quality studies showing an effect or lack of effect for each of the herbs and spices on inflammatory markers.

Figure 2
Figure 2. Number of studies and high-quality studies demonstrating the effect of herbs/spices in specific cardiometabolic biomarkers.Figure 2 identifies the main health markers measured and whether effects were seen for each of the herbs and spices in all studies and only in high-quality studies: (a) Number of studies showing an effect or lack of effect for each of the herbs and spices on blood glucose; (b) Number of high-quality studies showing an effect or lack of effect for each of the herbs and spices on blood glucose; (c) Number of studies showing an effect or lack of effect for each of the herbs and spices on insulin; (d) Number of high-quality studies showing an effect or lack of effect for each of the herbs and spices on insulin; (e) Number of studies showing an effect or lack of effect for each of the herbs and spices on blood lipids; (f) Number of high-quality studies showing an effect or lack of effect for each of the herbs and spices on blood lipids; (g) Number of studies showing an effect or lack of effect for each of the herbs and spices on inflammatory markers; (h) Number of high-quality studies showing an effect or lack of effect for each of the herbs and spices on inflammatory markers.

Table 1 .
Summary of results from included studies.