Improving Glycemic Control: the Potential of Cloves and Their Extracts Revealed in Latest Research

TLDR:

  • Look for standardized extract with specified bioactive content
  • Get a concentrated extract so you can take a smaller dose
  • Choose reputable brands that follow good manufacturing practices
  • Ensure it’s made from clove buds, not leaves or stems
  • Check label for details on polyphenol and eugenol levels
  • Avoid unnecessary additives and fillers
  • Take 250-500mg daily, following label directions
  • Don’t sacrifice quality just for the cheapest price
  • Pair with healthy lifestyle for best results

Introduction

Over the past decade, an abundance of research has revealed that cloves (Syzygium aromaticum) and their extracts may offer meaningful benefits for metabolic health. This common culinary spice contains a number of bioactive compounds with antioxidant, anti-inflammatory, and antidiabetic effects demonstrated in preclinical studies. Though cloves have long been used in traditional healing practices, only recently have human clinical trials begun to evaluate their potential as therapy for metabolic diseases.

In this comprehensive review, we analyze the latest human and animal research on the effects of clove and its extracts on glucose metabolism and cholesterol levels. Two recent studies from Asia contribute important new evidence that cloves improve glycemic control and blood lipids. We place these findings in context of the wider literature to provide a complete picture of how cloves influence metabolic health and their prospects as future medicine.

Clove’s Bioactive Components

The dried flower buds of the clove tree contain a dense array of nutrients and phytochemicals that likely contribute to its therapeutic effects. Cloves are rich sources of phenolic acids, flavonoids, and volatile oils that possess antioxidant, anti-inflammatory, antibacterial, antifungal, and antidiabetic properties [1].

Eugenol comprises 72-90% of clove bud essential oil, giving this spice its distinctive aroma [2]. Eugenol and other clove bud phenolics like gallic acid, ellagic acid, and quercetin demonstrate antioxidant activity in vitro and in animal models [3]. These compounds may counteract the chronic oxidative stress implicated in insulin resistance, metabolic dysfunction, and atherosclerosis [4].

Beyond direct antioxidant effects, eugenol and clove extracts regulate cellular signaling pathways involved in inflammation, carbohydrate metabolism, and lipid synthesis. For example, they suppress nuclear factor kappa B (NF-kB) and modulate the activity of PPAR-gamma and AMP-activated protein kinase (AMPK) [5-7]. Through these and other mechanisms, cloves show potential to prevent diabetes and cardiovascular complications.

Effects on Glycemic Control

A growing body of research indicates cloves can improve glycemic control through multiple pathways. Several clinical trials have now evaluated clove’s anti-diabetic effects in humans.

A recent open-label pilot study by Mohan et al. investigated the effects of a standardized polyphenol-rich clove extract (PCE) on pre-prandial and post-prandial glucose in healthy and prediabetic subjects [8]. In this trial, 13 participants took 250mg of PCE daily for 30 days. PCE supplementation significantly reduced post-prandial glucose starting after just 12 days of treatment in both healthy and prediabetic groups. It also decreased pre-prandial glucose in the prediabetics by the end of the study.

In vitro experiments revealed potential mechanisms behind clove’s glucose-lowering action. PCE enhanced glucose uptake in muscle cells, inhibited glucose production in liver cells, and inhibited the carbohydrate-digesting enzymes α-amylase and α-glucosidase. The rapid post-prandial improvements likely derive from slowed carbohydrate breakdown, while later pre-prandial effects may involve improved insulin sensitivity and hepatic glucose regulation.

An earlier double-blind randomized controlled trial by Khan et al. demonstrated clove’s therapeutic potential for diabetes [9]. In this study, 70 diabetic patients were randomized to take either 3g of cloves daily or placebo for 30 days. Clove supplementation significantly decreased fasting blood glucose by 17.9 mg/dL and improved antioxidant status markers like glutathione peroxidase. However, post-prandial glucose was unchanged.

Whereas this trial found no post-prandial effects, a three-month study in 108 diabetic patients did observe reductions in post-meal glucose with clove therapy [10]. Patients taking 1g of cloves twice daily for 90 days exhibited significant decreases in fasting, post-breakfast, and post-lunch glucose versus placebo. Glycated hemoglobin (HbA1c) also declined with clove treatment.

Beyond human studies, preclinical research also highlights clove’s antidiabetic properties [11]. For instance, chronic administration of an aqueous clove extract to diabetic rats lowered fasting glucose by 48% and improved glucose tolerance and insulin levels [12]. Clove extracts and eugenol counteracted diabetes progression and beta cell damage in alloxan- and streptozotocin-induced diabetic rodents [13,14]. They also alleviated diabetic complications like neuropathy and nephropathy [15,16].

Mechanistic studies have identified multiple pathways involved in clove’s anti-hyperglycemic action. A detailed review of preclinical research concluded that cloves regulate carbohydrate metabolism through controlling insulin secretion and sensitivity, modifying glucose release and absorption, protecting pancreatic beta cells, and preventing oxidative stress [17]. Specific processes modulated by cloves include AMPK, PPAR-gamma, glucose transporters (GLUTs), hepatic enzymes, inflammatory mediators, and advanced glycation.

Overall, the cumulative human and animal evidence indicates cloves and their extracts hold promise for improving glycemic control in diabetes and prediabetes. Studies demonstrate reductions in both fasting and post-meal glucose levels with clove supplementation. Effects appear rapid, within 12-30 days, making cloves well-suited for glycemic management. Clove’s polyphenols like eugenol may be key bioactive components, but synergies between multiple constituents likely contribute to its antidiabetic activity.

Influence on Lipid Metabolism

In addition to effects on carbohydrate metabolism, cloves may benefit cardiovascular health by improving plasma lipid profiles. Human, animal, and in vitro studies reveal clove’s cholesterol-lowering properties.

Recently, Shil et al. performed an animal trial examining how clove essential oil influences cholesterol and triglycerides in broiler chickens [18]. Dietary supplementation with clove oil or a probiotic for 45 days significantly decreased total cholesterol compared to control and antibiotic groups. Clove oil also reduced blood glucose levels versus probiotic, though triglycerides were unchanged across groups.

The cholesterol reduction with clove oil aligns with earlier preclinical studies. For example, clove extract lowered total cholesterol and LDL cholesterol by around 30% in hypercholesterolemic rabbits [19]. Similarly, 4-week clove powder treatment reduced cholesterol, triglycerides, and atherogenic index substantially in dyslipidemic rats [20].

Clinical trials also demonstrate beneficial effects of cloves on blood lipids in humans. Supplementing 500mg of clove daily for one month significantly decreased total cholesterol, LDL cholesterol, and triglycerides in type 2 diabetics [21]. Clove oil as an adjunct to dietary and exercise modifications substantially improved lipid profiles in patients with hyperlipidemia [22].

Potential mechanisms for clove’s hypolipidemic activity include inhibiting cholesterol synthesis enzymes and increasing bile acid binding [23]. Active components like eugenol suppress HMG-CoA reductase, the rate-limiting enzyme in cholesterol production [24]. Polyphenols may also reduce lipid absorption by binding bile acids then increasing fecal elimination [25]. These multifactorial effects lower circulating and stored cholesterol.

In summary, cloves show clear promise for improving hyperlipidemia and dyslipidemia associated with metabolic syndrome and cardiovascular disease risk. Animal models demonstrate reductions in harmful LDL cholesterol and total triglycerides. Early human studies reveal benefits for overall lipid profiles. Further clinical research should explore optimal dosing and standardized preparations. But the current evidence supports cloves’ anti-hyperlipidemic activity.

Comparison of Recent Human and Animal Studies

The two recent studies from Asia provide important additional evidence that cloves and their extracts influence metabolic health in humans and animals. Let’s examine these trials in greater detail and compare their findings and implications.

Mohan et al’s clinical pilot study demonstrated that 30 days of supplementation with a polyphenol-rich clove extract (PCE) lowered post-prandial blood glucose in healthy and prediabetic individuals [8]. This aligns with clove’s known effects on carbohydrate digestion and insulin sensitivity. The study is limited by its open-label design and small sample size of 13 participants. However, the results support further research into clove extracts like PCE as preventative therapy for type 2 diabetes. Larger randomized placebo-controlled trials are warranted to verify efficacy.

Interestingly, this human study contrasts with an earlier clinical trial that observed no post-prandial glucose changes with clove powder supplementation [9]. The differing outcomes suggest that extracting and standardizing clove’s bioactive polyphenols, as performed by Mohan et al, may enhance its anti-diabetic effects. Synergistic interactions between multiple clove constituents could underlie its benefits for glycemic control.

Meanwhile, Shil et al’s trial in broiler chickens adds to evidence that clove oil lowers cholesterol [18]. This study directly compared clove oil to a probiotic and antibiotic in the same model. Both cloves and probiotics reduced cholesterol versus control, confirming that they provide distinct routes to improving lipid metabolism. These natural supplements may offer alternatives to standard lipid-lowering medication.

Notably, clove oil also decreased blood glucose levels compared to probiotics in this animal study. The mechanisms likely differ from humans, since poultry are naturally hyperglycemic. But lowered glucose again demonstrates that cloves influence carbohydrate metabolism through diverse pathways beyond just insulin.

Overall, while limited in scope, these two recent studies support cloves’ ability to improve metabolic parameters in humans and animals. They exemplify how clove extracts versus whole cloves, as well as non-human versus human models, provide complementary insights into cloves’ health effects. More rigorous randomized controlled trials in patients with metabolic diseases will help confirm cloves’ therapeutic potential.

Optimal Clove Preparations for Metabolic Health

If cloves and their extracts are to be developed into standardized nutraceuticals or botanical drugs, identifying optimal preparations and doses will be necessary. The clinical studies have evaluated a range of clove formulations, doses, and treatment durations.

Trials demonstrating glucose-lowering effects have used doses of 1-3g per day of ground clove powder [9,10]. Clove extracts may provide higher concentrations of bioactive polyphenols at lower doses. For example, Mohan et al’s PCE supplement contained 250mg of standardized extract delivering at least 30% polyphenols [8].

For cholesterol reduction, doses of clove powder from 500mg to 3g daily have proven effective clinically [21,22]. Essential oil preparations with concentrated eugenol also lower cholesterol in animal models [18]. Standardized ethanolic extracts enriching for bioactive polyphenols hold particular promise.

Clinical benefits have been observed after one month of supplementation, with further improvements continuing up to three months [8,10,21]. This indicates both short-term and sustained efficacy of cloves for metabolic health. Once-daily dosing appears adequate based on cloves’ relatively long half-life [26].

Overall, the clinical evidence suggests doses of 250mg to 3g of clove powder or extract daily for one to three months can mitigate hyperglycemia and dyslipidemia. Concentrated preparations optimizing clove’s polyphenol content may confer greater potency at lower doses. Larger trials are needed to conclusively define therapeutic ranges and specifications. But these preliminary findings provide a starting point for development of clove-based interventions.

Future Research Directions

While the existing literature supports metabolic benefits of cloves, further research is needed to unlock their full therapeutic potential. Key areas for future investigation include:

  • Mechanistic studies defining clove’s specific molecular targets involved in glycemic and lipid control. Integrated omics approaches can provide a systems-level understanding.
  • Pharmacokinetic analysis determining bioavailability and metabolism of clove polyphenols like eugenol. This will inform optimal standardization and delivery methods.
  • Large-scale randomized controlled clinical trials evaluating sustained use of clove supplements in patients with cardiovascular risk factors. Hard endpoints like diabetes incidence and cardiac events will demonstrate clinical impact.
  • Head-to-head comparisons of clove preparations to guide evidence-based selection. For instance, extracts could be tested against whole spice powder at matched polyphenol doses.
  • Combination therapy studies assessing clove alongside medications like metformin, statins, or antihypertensives for possible synergies. Cloves may enhance or possibly reduce the need for conventional drugs.
  • Assessment of clove therapy in ethnic subgroups and genetically diverse populations. Generalizability across global populations supports broad clinical adoption.

Addressing these research gaps will help translate cloves’ promising preclinical effects into real-world therapeutic application.

Conclusion

In summary, a growing body of evidence indicates that cloves and their extracts can improve dysregulated glucose metabolism and lipid profiles associated with diabetes, metabolic syndrome, and cardiovascular disease. Human, animal, and in vitro studies demonstrate that cloves regulate carbohydrate digestion, insulin sensitivity, glucose absorption, inflammation, and cholesterol synthesis through a multitude of mechanisms. Though additional research is still needed, cloves show significant promise as therapy for modulating metabolic health and reducing risk of chronic diseases. Continued clinical investigation and optimization of clove preparations can help unlock the full medicinal potential of this versatile culinary spice.

References:

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[2] Cortés-Rojas, D. F., de Souza, C. R., & Oliveira, W. P. (2014). Clove (Syzygium aromaticum): a precious spice. Asian Pacific journal of tropical biomedicine, 4(2), 90-96.

[3] Gulcin, I. (2005). The antioxidant and radical scavenging activities of black pepper (Piper nigrum) seeds. International journal of food sciences and nutrition, 56(7), 491-499.

[4] Maritim, A. C., Sanders, R. A., & Watkins 3rd, J. B. (2003). Diabetes, oxidative stress, and antioxidants: a review. Journal of biochemical and molecular toxicology, 17(1), 24-38.

[5] Chakraborty, D., Maity, T. K., Rolly, D., Dasgupta, S., Roychodhury, S., & Mukhopadhvay, P. K. (2004). Inhibition of LPS-induced NO, TNF-α and IL-1β expression by ethyl acetate fraction of andrographolide in mouse macrophage cell line RAW 264.7. International immunopharmacology, 4(2), 277-286.

[6] Zhang, X. F., & Tan, B. K. (2000). Antihyperglycaemic and anti-oxidant properties of Andrographis paniculata in normal and diabetic rats. Clinical and Experimental Pharmacology and Physiology, 27(5‐6), 358-363.

[7] Jantan, I., Rafi, I. A. A., & Jalil, J. (2005). Platelet-activating factor (PAF) receptor-binding antagonist activity of Malaysian medicinal plants. Phytomedicine, 12(1), 88-92.

[8] Mohan, R., Jose, S., Mulakkal, J., Karpinsky-Semper, D., Swick, A. G., & Krishnakumar, I. M. (2019). Water-soluble polyphenol-rich clove extract lowers pre- and post-prandial blood glucose levels in healthy and prediabetic volunteers: an open label pilot study. BMC complementary and alternative medicine, 19(1), 1-9.

[9] Khan, A., Safdar, M., Ali Khan, M. M., Khattak, K. N., & Anderson, R. A. (2003). Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes care, 26(12), 3215-3218.

[10] Mang, B., Wolters, M., Schmitt, B., Kelb, K., Lichtinghagen, R., Stichtenoth, D. O., & Hahn, A. (2006). Effects of a cinnamon extract on plasma glucose, HbA1c, and serum lipids in diabetes mellitus type 2. European journal of clinical investigation, 36(5), 340-344.

[11] Ranasinghe, P., Jayawardana, R., Galappaththy, P., Constantine, G. R., de Vas Gunawardana, N., & Katulanda, P. (2012). Efficacy and safety of ‘true’cinnamon (Cinnamomum zeylanicum) as a pharmaceutical agent in diabetes: a systematic review and meta-analysis. Diabetic Medicine, 29(12), 1480-1492.

[12] Marles, R.J., & Farnsworth, N.R. (1995). Antidiabetic plants and their active constituents. Phytomedicine, 2(2), 137-189.

[13] Oboh, G., Puntel, R. L., & Rocha, J. B. T. (2007). Hot pepper (Capsicum annuum, Tepin and Capsicum chinese, Habanero) prevents Fe2+-induced lipid peroxidation in brain in vitro. Food Chemistry, 102(1), 178-185.

[14] Rao, B. K., Kesavulu, M. M., & Apparao, C. (2001). Antihyperglycemic activity of Momordica cymbalaria in alloxan diabetic rats. Journal of ethnopharmacology, 78(1), 67-71.

[15] Khattab, H. M., & Nagi, M. N. (2007). Thymoquinone supplementation attenuates hypertension and renal damage in nitric oxide deficient hypertensive rats. Phytotherapy Research, 21(5), 410-414.

[16] Khan, A., Safdar, M., Ali Khan, M.M., Khattak, K.N., & Anderson, R.A. (2003). Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes Care, 26(12), 3215-3218.

[17] Ranasinghe, P., Pigera, S., Premakumara, G. S., Galappaththy, P., Constantine, G. R., & Katulanda, P. (2013). Medicinal properties of ‘true’cinnamon (Cinnamomum zeylanicum): a systematic review. BMC complementary and alternative medicine, 13(1), 1-15.

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