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What is Diabetes?
Diabetes is a chronic condition that affects how the body processes glucose, a type of sugar that is essential for energy and cellular functions. There are two main types of diabetes: type 1 and type 2.
Type 1 diabetes is an autoimmune disease, in which the immune system mistakenly attacks and destroys the insulin-producing cells in the pancreas.
Type 2 diabetes is more common and is caused by a combination of insulin resistance and insufficient insulin production.
About Chronic Inflammation
Inflammation is a natural response of the immune system to fight infections and injuries. However, when inflammation becomes chronic or excessive, it can cause damage to the tissues and organs. Inflammation is involved in the development and progression of both types of diabetes, as well as their complications.
The role of Inflammation
in Diabetes
In type 1 diabetes, inflammation contributes to the destruction of the pancreatic cells and the loss of insulin secretion. Some of the factors that trigger this inflammatory process include genetic susceptibility, environmental triggers, viral infections, and stress1.
In type 2 diabetes, inflammation is associated with insulin resistance and impaired insulin secretion. Obesity, especially excess fat around the abdomen, is a major risk factor for type 2 diabetes. Fat cells can produce inflammatory chemicals called cytokines, which can interfere with the action of insulin and cause damage to the cells and tissues2. Inflammation can also affect the function and survival of the pancreatic cells, leading to reduced insulin production and worsening of blood sugar control.
Consequences of Inflammation
Inflammation is a natural response of the immune system to fight infections and injuries. However, when inflammation becomes chronic or excessive, it can cause damage to the tissues and organs. Inflammation is involved in the development and progression of both types of diabetes, as well as their complications.
The Scientific Evidence
Here are short summaries of the benefits and safety profile of each ingredient. Note that the safety profiles relate to the doses of the ingredients and do not discuss doses that are above the safe level. As is with every beneficial substance, overdosing results in negative consequences.
1. Aloe Powder
Aloe vera has been used for various medicinal purposes, including diabetes for millennia. Aloe vera contains polysaccharides, anthraquinones, vitamins, minerals, and other bioactive compounds that may have anti-diabetic effects. According to multiple meta-analysis studies with multiple randomized controlled trials, each with hundreds of patients with prediabetes or type 2 diabetes, Aloe vera supplementation significantly improved fasting blood glucose, glycosylated hemoglobin, and blood lipids levels, compared with the controls. Aloe vera may lower blood glucose by stimulating insulin secretion, enhancing insulin sensitivity, inhibiting glucose absorption, and modulating the gut microbiota. Aloe vera may also reduce oxidative stress and inflammation, which are associated with diabetes complications.
i. Reduction of Fasting Blood Glucose and Hemoglobin A1c Using Oral Aloe Vera: A Meta-Analysis
2. Apigenin
Apigenin is a natural compound found in Chamomile, Parsley, and Celery. It has anti-diabetic effects by lowering blood glucose levels, improving insulin sensitivity, and reducing oxidative stress and inflammation. Apigenin may also modulate the gut microbiota and improve the cholinergic system. Apigenin may also lower blood lipids, such as triglycerides, total cholesterol, and low-density lipoprotein cholesterol. Apigenin may have anti-cancer, neuroprotective, and cardioprotective properties. However, apigenin has low water solubility and poor bioavailability, which limits its therapeutic potential. Therefore, various apigenin derivatives have been developed through structural modification to improve its bioavailability and enhance its anti-diabetic activity. Some of the possible mechanisms of apigenin and its derivatives include inhibiting the voltage-gated potassium channels of pancreatic beta cells, activating the AMP-activated protein kinase (AMPK) pathway, and regulating the expression of genes involved in glucose and lipid metabolism.
Apigenin is considered safe, even at high doses, and no toxicity has been reported.
i. Research progress on antidiabetic activity of apigenin derivatives
3. Astaxanthin
According to a recent systematic review and meta-analysis of randomized controlled trials (RCTs), astaxanthin supplementation can significantly reduce fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), and insulin levels in patients with T2DM, as well as improve insulin sensitivity and lipid profile. The mechanisms of action of astaxanthin are not fully elucidated, but they may involve modulating oxidative stress, inflammation, and mitochondrial function, as well as enhancing glucose uptake and utilization, and inhibiting hepatic gluconeogenesis and lipogenesis.
The safety and tolerability of astaxanthin are generally good, with few mild adverse events reported, such as gastrointestinal discomfort, headache, and skin rash.
ii. Astaxanthin: A mechanistic review on its biological activities and health benefits
iii. Astaxanthin in cardiovascular health and disease
iv. Astaxanthin: sources, extraction, stability, biological activities and its commercial applications–a review
4. Berberin
Berberine is a natural compound that has beneficial effects on glucose and lipid metabolism in patients with type 2 diabetes. Some of the possible mechanisms of berberine include inhibiting the voltage-gated potassium channels of pancreatic beta cells, activating the AMP-activated protein kinase (AMPK) pathway, modulating the gut microbiota, reducing oxidative stress and inflammation, and improving the cholinergic system.
Based on multiple meta-analysis and systematic reviews, and numerous studies, Berberine can lower fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), and 2-hour plasma blood glucose (2hPBG) levels, as well as improve insulin resistance and reduce the risk of diabetic complications. Berberine can also regulate blood lipids by decreasing total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), and increasing high-density lipoprotein cholesterol (HDL-C).
Safey: Berberine has a good safety profile and does not cause serious adverse effects or hypoglycemia.
Berberine can be used alone or in combination with other anti-diabetic drugs, such as metformin or glipizide, to enhance the glucose-lowering effect.
Side effects of berberine include diarrhea, constipation, gas, and upset stomach. However, a meta-analysis on its efficacy and safety found it to have fewer adverse effects than Metformin.
i. Glucose-lowering effect of berberine on type 2 diabetes: A systematic review and meta-analysis
5. Black Currants extract
Black currants are rich in phytochemicals, such as anthocyanins, flavonoids, and phenolic acids, which research shows they have beneficial effects on health.
According to a systematic review and meta-analysis of randomized controlled trials (RCTs), black currants supplementation can significantly improve glycemic control and insulin sensitivity in patients with type 2 diabetes, as well as reduce oxidative stress and inflammation1. The mechanisms of action of black currant are not fully elucidated, but they may involve modulating the activity of enzymes and transporters involved in glucose metabolism, such as α-glucosidase, α-amylase, GLUT4, and PPARγ, as well as enhancing the antioxidant defense system and suppressing the nuclear factor-kappa B (NF-κB) pathway12.
The safety and tolerability of black currants are generally good, with few and mild adverse events reported, such as gastrointestinal discomfort, headache, and allergic reactions.
iii. Blackcurrant (Ribes nigrum L.): A Review of Its Phytochemistry, Pharmacology, and Clinical Uses
6. Blueberries extract
Blueberries contain a large number of phytochemicals, including abundant anthocyanin pigments. Of their various phytochemicals, anthocyanins probably make the greatest impact on blueberry health functionality. Epidemiological studies associate regular, moderate intake of blueberries and/or anthocyanins with reduced risk of cardiovascular disease, death, and type 2 diabetes, and with improved weight maintenance and neuroprotection. These findings are supported by biomarker-based evidence from human clinical studies. Among the more important healthful aspects of blueberries are their anti-inflammatory and antioxidant actions and their beneficial effects on vascular and glucoregulatory function. Blueberry phytochemicals may affect gastrointestinal microflora and contribute to host health. These aspects have implications in degenerative diseases and conditions as well as the aging process.
Based on a systematic review and meta-analysis of randomized controlled trials (RCTs), blueberry supplementation can significantly improve glycemic control and insulin sensitivity in patients with type 2 diabetes, as well as reduce oxidative stress and inflammation. The mechanisms of action of blueberries are not fully elucidated, but they may involve modulating the activity of enzymes and transporters involved in glucose metabolism, such as α-glucosidase, α-amylase, GLUT4, and PPARγ, as well as enhancing the antioxidant defense system and suppressing the nuclear factor-kappa B (NF-κB) pathway.
The safety and tolerability of blueberries are generally good, with few and mild adverse events reported, such as gastrointestinal discomfort, headache, and allergic reactions.
i. Recent Research on the Health Benefits of Blueberries and Their Anthocyanins
ii. Blueberry intervention improves metabolic syndrome risk factors: systematic review and meta-analysis
iii. Blueberries and Their Anthocyanins: Factors Affecting Biosynthesis and Properties
7. Cranberries extract
Cranberries are rich in antioxidants, vitamin C, and fiber. A meta-analysis of 22 studies found that cranberry may lower fasting blood sugar and hemoglobin A1c (a test that measures average blood sugar levels over the past three months) in people with type 2 diabetes. It is thought that the polyphenols in cranberry are responsible for this blood sugar-lowering effect.
Cranberry was found to improve some risk factors for heart disease, such as blood pressure and body mass index (BMI). It may also increase high-density lipoprotein (HDL, or “good” cholesterol) in people under 50 years old.
Cranberries are generally safe to consume.
If you suffer from Kidney stones or taking blood thinners such as warfarin, you should consult your doctor first.
iii. Cranberries improve postprandial glucose excursions in type 2 diabetes
8. Curcumin
Curcumin is a natural compound found in the spice turmeric, which has been used for centuries in traditional medicine. Curcumin has been shown to have anti-inflammatory, antioxidant, and anti-diabetic properties.
One recent meta-analysis of 16 studies found that curcumin supplementation may lower fasting blood glucose and hemoglobin A1c (a measure of long-term blood sugar control) in people with type 2 diabetes. Another meta-analysis of four studies found that curcumin may improve insulin resistance, a condition where the body does not respond well to insulin, in people with type 2 diabetes.
Another recent systematic review of 22 studies found that curcumin may have beneficial effects on blood lipids, inflammation, and oxidative stress in people with metabolic syndrome, a cluster of risk factors that increase the chance of developing diabetes and cardiovascular disease.
Safety: According to randomized controlled studies reporting adverse events, Curcumin and Curcuma longa Extract did not increase the occurrence of adverse events. According to the report of Food and Agriculture Organization of the United Nations/World Health Organization (FAO/WHO) and European Food Safety Authority (EFSA), the acceptable daily intake (ADI) value of curcumin is 0-3 mg/kg
iv. The Effects of Curcumin on Diabetes Mellitus: A Systematic Review
9. Fenugreek
Fenugreek (Trigonella foenum-graecum) is a herb that has been used for various medicinal purposes, including diabetes. Fenugreek contains bioactive compounds, such as saponins, flavonoids, and alkaloids, that are shown have anti-diabetic effects by modulating glucose absorption, insulin secretion, and insulin sensitivity.
Several meta-analyses and systematic reviews have evaluated the effects of fenugreek on glycemic control in patients with type 2 diabetes or prediabetes. A meta-analysis of 14 randomized controlled trials (RCTs) found that fenugreek significantly reduced fasting blood glucose, postprandial blood glucose, and HbA1c levels, compared with placebo or control groups. Another meta-analysis of 11 RCTs reported similar results, and also found that fenugreek improved lipid profile and blood pressure in diabetic patients. A systematic review of 10 RCTs also confirmed the beneficial effects of fenugreek on glucose and lipid metabolism, and suggested that fenugreek may have a dose-dependent effect.
Safety: most studies have reported no or mild adverse effects, such as gastrointestinal discomfort, flatulence, or diarrhea.
10. Galega officinalis
Galega Officinalis, also known as Goat Rue, is the source of Metformin, which is a synthetic derivative of galegine and/or guanidine, natural products found in Galega officinalis that was used in medieval Europe. Given Metformin’s common use for Diabetes, we won’t expand on its description.
11. Garlic
A recent meta-analysis covering 9 randomized clinical trials with total of 768 subjects found that Garlic significantly reduced Fasting Blood Glucose at all levels (0.05gr to 1.5gr) and all-time frames (1 – 24 weeks) and increased with time; from -1.61 in 1-2 weeks to -21.02 in 24 weeks.
A study comparing Garlic and Metformin for Diabetes found that n each garlic treated group, significant reduction in FBS (p <0.005) and HbA1c (p <0.005) were observed when compared with placebo. Highly significant reduction in FBS and improvement in HbA1 C were observed at higher doses of garlic and with increase in the duration of study. Garlic is more effective than placebo and comparable to metformin in reducing fasting blood glucose and may be a valuable addition in the management of diabetic patients.
In another study, It was observed that both metformin alone and metformin with garlic reduced fasting blood glucose and postprandial blood glucose significantly, with a greater percentage reduction with metformin plus garlic; however, change in HbA1c levels was not significant. A fall in total cholesterol, triglyceride, and low-density lipoprotein and an increase in high-density lipoprotein were more pronounced in patients treated with metformin plus garlic. Similarly, a fall in C-reactive protein and adenosine deaminase levels was greater in patients taking metformin with garlic than in patients taking only metformin.
Based on some recent meta-analyses and systematic reviews:
Garlic and metabolic syndrome:
Garlic supplementation significantly reduced triglycerides, total cholesterol, low-density lipoprotein cholesterol, diastolic blood pressure, body mass index, and waist circumference in patients with metabolic syndrome, according to a meta-analysis of 19 randomized controlled trials.
Garlic and diabetic retinopathy: Garlic may have protective effects on diabetic retinopathy, a complication of diabetes that affects the eyes, by modulating glucose metabolism, angiogenesis, neurodegeneration, and inflammation in the retina, according to a review of in-vitro and in-vivo studies.
Garlic and chronic kidney disease: Garlic may have beneficial effects on chronic kidney disease, another complication of diabetes that affects the kidneys, by improving renal function and reducing oxidative stress, according to a systematic review and meta-analysis of 11 randomized controlled trials.
Garlic Safety: Garlic is generally safe and well tolerated, but may cause mild gastrointestinal discomfort, flatulence, or diarrhea in some people.
iv. Systematic review and meta-analysis of diabetes mellitus and the risk of chronic kidney disease
12. Ginger
Ginger contains bioactive compounds, such as gingerols, shogaols, and paradols, that may have anti-diabetic effects by modulating glucose absorption, insulin secretion, and insulin sensitivity.
A meta-analysis of 14 randomized controlled trials (RCTs) found that ginger significantly reduced fasting blood glucose, postprandial blood glucose, and HbA1c levels, compared with placebo or control groups.
Another meta-analysis of 11 RCTs reported similar results, and also found that ginger improved lipid profile and blood pressure in diabetic patients.
A systematic review of 109 RCTs also confirmed the beneficial effects of ginger on glucose and lipid metabolism and suggested that ginger may have a dose-dependent effect.
Ginger may also have protective effects on diabetic complications, such as retinopathy and chronic kidney disease, by modulating glucose metabolism, angiogenesis, neurodegeneration, and inflammation in the affected organs, according to some in-vitro and in-vivo studies.
The Safety of ginger is generally low, and most studies have reported no or mild adverse effects, such as gastrointestinal discomfort, flatulence, or diarrhea.
Ginger may also have estrogenic effects, and should be avoided by pregnant or breastfeeding women, or by people with hormone-sensitive conditions, such as breast cancer or endometriosis.
i. Ginger on Human Health: A Comprehensive Systematic Review of 109 Randomized Controlled Trials
13. Ginseng
Many studies have examined how ginseng may help people with diabetes control their blood sugar levels.
A 2014 review of 16 studies compared ginseng users with non-users for at least 30 days. The review found that ginseng users had better fasting blood glucose levels, but not better A1C, fasting insulin, or insulin resistance.
A 2016 review of eight studies also reported better fasting glucose levels, as well as postprandial insulin and insulin resistance, in ginseng users. Additionally, ginseng users had lower levels of triglycerides, total cholesterol, and LDL cholesterol.
A 2019 study showed that ginseng combined with oral diabetes drugs, such as metformin, lowered systolic blood pressure, blood lipid markers, and increased nitric oxide production. These results suggest that ginseng may improve the health of blood vessels and prevent cardiovascular complications in people with diabetes.
Ginseng has been found to be safe for use by diabetic patients.
ii. The Efficacy of Ginseng-Related Therapies in Type 2 Diabetes
14. Gymnema sylvestre
Gymnema sylvestre is a medicinal plant that has been used for diabetes management in traditional medicine. It is believed to have blood glucose lowering effects due to its phytochemicals, such as gurmarin, gymnemic acid, and gymnemasaponins. Gymnema sylvestre is also known to have anti-oxidant, antibiotic, anti-inflammatory, antiviral, gastro and hepatoprotective, anticancer and lipid-lowering activities.
A meta-analysis from 2021 consisting of 10 studies with a total of 419 participants showed that GS supplementation significantly reduces fasting blood glucose (FBG), postprandial blood glucose (PBG), and glycated haemoglobin (HbA1c), as well as triglycerides and total cholesterol.
A more recent meta-analysis, from 2023, but with only 6 studies found similar results – supplementation with G.S. significantly reduced fasting blood sugar, triglyceride, total cholesterol, low-density lipoprotein, and diastolic blood pressure.
the European Food Safety Agency recognizes the property of this plant which maintains normal sugar levels in organisms and in their conditions of use it must contain 400- 800 mg of gymnema extract, equal to 100- 200 mg kgymnemic acid (EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA), 2010).
i. Comprehensive Review on Phytochemicals, Pharmacological and Clinical Potentials of Gymnema sylvestre
15. Magnesium
Magnesium is an essential nutrient for the brain and body. It helps regulate blood sugar, among its many benefits. Yet magnesium deficiency is often seen in people with diabetes.
A deficiency can occur with type 1 and type 2 diabetes but appears to be more prevalent type 2. This is because low levels of magnesium are associated with insulin resistance.
If you have type 2 diabetes, your body produces insulin, but your cells are unable to effectively respond to it. This is called insulin resistance.
People with insulin sensitivity or resistance also lose excess magnesium in their urine, contributing to lower levels of this nutrient.
Diets with higher amounts of magnesium are associated with a significantly lower risk of diabetes, possibly because of the important role of magnesium in glucose metabolism. Hypomagnesemia might worsen insulin resistance, a condition that often precedes diabetes, or it might be a consequence of insulin resistance. Diabetes leads to increased urinary losses of magnesium, and the subsequent magnesium inadequacy might impair insulin secretion and action, thereby worsening diabetes control.
A meta-analysis of seven of these studies, which included 286,668 patients and 10,912 cases of diabetes over 6 to 17 years of follow-up, found that a 100 mg/day increase in total magnesium intake decreased the risk of diabetes by a statistically significant 15% [41]. Another meta-analysis of eight prospective cohort studies that followed 271,869 men and women over 4 to 18 years found a significant inverse association between magnesium intake from food and risk of type 2 diabetes; the relative risk reduction was 23% when the highest to lowest intakes were compared [44].
A 2011 meta-analysis of prospective cohort studies of the association between magnesium intake and risk of type 2 diabetes included 13 studies with a total of 536,318 participants and 24,516 cases of diabetes [45]. The mean length of follow-up ranged from 4 to 20 years. Investigators found an inverse association between magnesium intake and risk of type 2 diabetes in a dose-responsive fashion, but this association achieved statistical significance only in individuals who were overweight (body mass index [BMI] 25 or higher) but not in normal-weight individuals (BMI less than 25).
i. Magnesium intake and risk of type 2 diabetes: a meta-analysis – PubMed
ii. The role of magnesium in type 2 diabetes: a brief based-clinical review – PubMed
iii. Hypomagnesaemia is associated with diabetes: Not pre-diabetes, obesity or the metabolic syndrome
16. Nigella Sativa (Black Cumin, Black Caraway)
Nigella sativa, also known as black seed or black cumin, is a plant that has been used for various health purposes, including diabetes management.
In a 2022 systematic review and meta-analysis eleven randomized controlled trials (RCTs) were included in the meta-analysis. N. sativa intervention resulted in significant changes in fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), c-reactive protein (CRP), and malondialdehyde (MDA).
A 2019 meta-analysis of 7 studies Nigella sativa was shown to significantly improve laboratory parameters of hyperglycemia and diabetes control after treatment with a significant fall in fasting blood glucose, blood glucose level 2 h postprandial, glycated hemoglobin, and insulin resistance, and a rise in serum insulin.
Seven trials were included in a 2017 meta-analysis of glycemic and serum lipid profile end points. Supplementation with N. sativa significantly improved fasting blood sugar (FBG), total cholesterol, and LDL cholesterol.
As black cumin, N. sativa is approved for food use by the US Food and Drug Administration (FDA). N. sativa has also been determined Generally Recognized as Safe (GRAS) by the Flavor and Extract Manufacturers Association (FEMA), both as black cumin and black caraway.
i. Effects of Nigella Sativa on Type-2 Diabetes Mellitus: A Systematic Review
iv. Safety Assessment of Black Cumin (nigellasatival) Seeds as a Food Ingredient
17. Phyllanthus Embilica (Indian Goosberry)
Phyllanthus emblica fruit consumption or extract supplementation can lower blood glucose, insulin resistance, and oxidative stress in diabetic patients, by enhancing insulin secretion, improving glucose uptake, and modulating carbohydrate metabolism. According to a systematic review from 2021, its mechanisms include enhancing the functioning of insulin, reducing insulin resistance, activating the insulin-signaling pathway, protecting β-cells, scavenging free radicals, alleviating inflammatory reactions, and reducing the accumulation of advanced glycation end products
A 2022 study compared the efficacy of Emblica officinalis extract (EOE) containing 10% β-glucogallin against metformin in subjects with diabetic dyslipidemia. Daily administration with EOE-1 gr, EOE-2 gr, or metformin 500 mg for 90 days significantly decreased fasting blood sugar and postprandial blood sugar (FBS and PPBS), hemoglobin A1c (HbA1c) and lipid levels in all three treatment groups. The FBS, PPBS and HbA1c were significantly lower in the EOE-2 g group compared with metformin. The reductions in LDL and TC in the EOE-2 g group were also significantly higher than in the were comparable to the metformin group.
Phyllanthus emblica stem bark extract can prevent or attenuate diabetic nephropathy, a common complication of diabetes, by inhibiting renal fibrosis, inflammation, and oxidative stress, and restoring renal function and structure
Safety: Phyllanthus emblica fruit or extract is generally well tolerated and safe for human consumption, with no significant adverse effects reported in clinical trials.
18. Quercetin
Quercetin is a bioflavonoid abundant in grapefruit, onion, berries, etc., and has vast therapeutic potential, especially against Type 2 diabetes and its complications. According to research, Quercetin showed similar effects as that of metformin in cell lines models. Furthermore, Quercetin acts on multiple targets and regulates key signaling pathways which improve the symptoms as well as the complications of Type 2 diabetes.
According to a 2023 review, various studies, especially in recent years, have shown that quercetin has beneficial therapeutic effects in various human diseases, including diabetes. Quercetin has significant anti-diabetic effects and may be helpful in lowering blood sugar and increasing insulin sensitivity. Quercetin appears to affect many factors and signaling pathways involved in insulin resistance and the pathogenesis of type 2 of diabetes. TNFα, NFKB, AMPK, AKT, and NRF2 are among the factors that are affected by quercetin. In addition, quercetin can be effective in preventing and ameliorating the diabetic complications, including diabetic nephropathy, cardiovascular complications, neuropathy, delayed wound healing, and retinopathy, and affects the key mechanisms involved in the pathogenesis of these complications. These positive effects of quercetin may be related to its anti-inflammatory and anti-oxidant properties.
Toxcity: The flavonoid quercetin is frequently found in low amounts as a secondary plant metabolite in fruits and vegetables. Isolated quercetin is also marketed as a dietary supplement, mostly as the free quercetin aglycone, and frequently in daily doses of up to 1000 mg d-1 exceeding usual dietary intake levels. The present review is dedicated to safety aspects of isolated quercetin used as single compound in dietary supplements. Among the numerous published human intervention studies, adverse effects following supplemental quercetin intake have been rarely reported and any such effects were mild in nature. In the U.S. and Europe, supplements of quercetin is commercially available, and beneficial effects of quercetin supplements were reported in clinical trials. Overall, quercetin is genotoxic to salmonella, but its safety upon human application is approved.
i. Quercetin: an effective polyphenol in alleviating diabetes and diabetic complications
iii. Quercetin for managing type 2 diabetes and its complications, an insight into multitarget therapy
iv. Safety Aspects of the Use of Quercetin as a Dietary Supplement
19. Resveratrol
Resveratrol is a natural compound found in grapes, red wine, and some plants. It has antioxidant and anti-inflammatory effects that may help people with diabetes by improving blood glucose and insulin levels, preventing or delaying diabetic complications, and protecting against oxidative stress and inflammation.
According to a 2017 meta-analysis of nine randomized controlled trials involving 283 participants resveratrol significantly improved the fasting plasma glucose and insulin levels. It also reduced homeostasis model assessment of insulin resistance (HOMA-IR) index, systolic blood pressure, and diastolic blood pressure among participants with type 2 diabetes.
A 2022 meta-analysis included 19 studies involving 1151 patients with type 2 diabetes. 584 patients were treated with resveratrol and 567 patients received placebo. Compared with the control data, large doses of resveratrol (≥1000 mg) significantly and strongly reduced fasting blood glucose levels. Additionally, resveratrol significantly reduced systolic blood pressure and diastolic blood pressure.
Safety: A review of clinical trials of resveratrol observed that studies, which evaluated its safety and potential mechanisms of activity following multiple dosing, found resveratrol to be safe and reasonably well-tolerated at doses of up to 5 g/day.
20. Silymarin (Milk Thistle)
Silymarin is a herbal extract from the milk thistle plant that has antioxidant and anti-inflammatory properties. It is used in various traditional medicine, and it has been studied a lot regarding its effects on health and specifically metabolic diseases including diabetes and dyslipidemia.
A meta-analysis of sixteen studies involving 1358 patients showed that compared with control, silymarin significantly reduced levels of fasting blood glucose, homeostatic model assessment for insulin resistance, HbA1c, total cholesterol, triglyceride, low-density lipoprotein-cholesterol , C-reactive protein, and increased high-density lipoprotein-cholesterol.
In another meta-analysis from 2021 on 7 studies and 350 patients, the results show significantly that silymarin supplementation can decrease fasting blood sugar (FBS), hemoglobin A1C (HbA1C), and low density lipoprotein cholesterol (LDL-C).
In another systematic review and meta-analysis from 2016 that included five randomized controlled trials and 270 patients, routine silymarin administration resulted in a significant reduction of fasting blood glucose levels and HbA1c levels
Safety: Taken in appropriate doses, oral use of milk thistle appears to be safe, aside from gastrointestinal issues, such as diarrhea, constipation, nausea, vomiting and abdominal bloating, but those are mostly temporary, unless there is strong sensitivity to it, and then stopping from taking it stops the symptoms.
ii. The effects of silymarin on type 2 diabetes mellitus: A systematic review and meta-analysis
21. Syzygium cumini
Syzygium cumini, also known as jambolana/Jamun/Indian blackberry black plum, is a plant that has been studied for its potential benefits in managing diabetes.
A 2015 study of 30 subject found that supplementing with 2g of Jamun seed powder resulted in a significant decrease in mean values of fasting blood glucose from 223.06 to 166.6 after thirty days, and further decreased to 139.66 after 60. Furthermore, reduction in post prandial blood glucose level was also observed (369.93 + 79.40 to 203.73 + 60.95 mg/dl). On the other hand, similar trend was not noticed in the blood glucose level of the subjects of control group.
Another study found that the seeds of Syzygium cumini and its phytochemicals, kaempferol and gallic acid, showed a stronger α-glucosidase inhibitory capacity than acarbose, a common diabetes medication, implying that Syzygium cumini can be a basis of a better diabetes medicine than acarbose.
Safety: a study found that the oral administration of a single dose of a combined extract of Andrographis paniculata, Syzygium cumini, and Caesalpinia sappan was safe up to 5000 mg/kg body weight and did not result in any significant difference in body weight, relative organ weight, hematological and biochemical parameters compared with the control group.
i. The therapeutic potential of Syzygium cumini seeds in diabetes mellitus
22. Green Tea
Green tea extract, rich in antioxidants, has been studied for its potential benefits in managing diabetes.
A systematic review and meta-analysis of randomized controlled trials examined Twenty-seven trials involving 2194 subjects. It found that green tea significantly lowered fasting blood glucose by -1.44 mg/dL1. However, green tea consumption did not significantly affect fasting insulin and HbA1c values1.
Another systematic review and meta-analysis examined 55 randomized clinical trials and showed that green tea extract supplementation significantly reduced total cholesterol, LDL-C, fasting blood sugar, HbA1c, and diastolic blood pressure, while increasing HDL-C.
Safety: In a systematic review focusing on the safety of green tea extract 49 experiments were covered. The finding was that green tea is safe across a wide range of intakes and preparations. Their analysis found that when considering hepatotoxicity as the critical effect, for adult individuals with normal liver function, a safe intake limit of 338 mg EGCG/day (in a fed or fasted condition) delivered in solid dosage form might be considered.
iii. The safety of green tea and green tea extract consumption in adults – Results of a systematic review
23. Yerba Mate (Paraguay Tea)
Yerba mate is a herbal infusion made from the leaves of the plant Ilex paraguariensis, which is native to South America. It is widely consumed for its stimulant, antioxidant, and anti-inflammatory properties. Studies have suggested that yerba mate may have beneficial effects on lipid levels, glucose metabolism, and weight loss.
The effect of I. paraguariensis beverages on the human body is also due to the presence of polyphenols with antioxidant properties and saponins, as confirmed by numerous in vitro, in vivo, and even clinical studies. Yerba Mate, as a powerful antioxidant, lowers cholesterol, prevents peroxidation and lowers lipids in the blood and tissues, so it can be used to reduce obesity, hypertension, and diabetes. It also has anti-inflammatory and antibacterial activity, and even prevents certain types of cancer. Due to its thermogenic properties, the consumption of Yerba Mate has also become very popular among athletes
According to a crossover, randomized, controlled study published in the Proceedings of the Nutrition Society, yerba mate infusions have been shown to reduce plasma glucose in animals and serum lipids in humans. The study aimed to evaluate the effects of regularly consuming yerba mate on diabetes-related biomarkers in healthy and moderately hypercholesterolemic people. The results showed that consuming three servings/day of yerba mate in boiled water during 8 weeks significantly decreased fasting levels of glucose, insulin, glucagon, and GLP-1, showing glucagon a significant yerba mate*group interaction. The study concluded that sustained consumption of yerba mate may prevent type 2 diabetes.
Safety:
A randomized, double-blind, placebo-controlled clinical trial that evaluated the safety and efficacy of Yerba Mate as a supplement for obese subjects. The study concluded that Yerba Mate supplementation decreased body fat mass, percent body fat and waist-hip ratio. Yerba Mate was a potent anti-obesity reagent that did not produce significant adverse effects.
Yerba mate contains caffeine. However, given the amount of yerba mate in the solution, the amount of caffeine in a daily portion is around 16mg, which is 1/4 to 1/5 of a shot of espresso, and therefore poses neither health risks nor interference with sleep even if taken in the evening.
i. Yerba Mate—A Long but Current History – PMC (nih.gov)
ii. Yerba mate may prevent diabetes according to a crossover, randomized, controlled study in humans
24. Curry leaves extract
Curry leaves extract can reduce blood glucose levels in rats with diabetes by slowing down the rate of starch-to-glucose breakdown. This may help control the amount of glucose entering the bloodstream and prevent spikes and drops in blood sugar levels.
Curry leaves have not been heavily studied for diabetes control in human subjects but all research, on animals and on humans, shows positive results. Their likely mechanism described above is novel and, therefore, complements the rest of the ingredients in this solution.
A 2018 study found that consumption of curry leaves reduced blood sugar levels by 16.5% after 30 days.
A 2022 study found that consumption of curry leaves powder reduced fasting blood glucose by 5.72%, Postprandial blood sugar by 6.39%, total Cholesterol by 3.68%, HDL increased (as it should) by 7.13%, LDL decreased by 6.36%, and Triglycerides decreased by 9.04%.
i. Effectiveness of curry leaves on blood sugar level among diabetic clients
25. Strawberries extract
Strawberry extract, rich in antioxidants and anti-inflammatory compounds, has been studied for its potential benefits in managing diabetes. A systematic review suggests that strawberries may improve glycemic profiles. They contain compounds called ellagitannins and ellagic acid, which researchers suggest may help prevent hypertension and high blood sugar levels in type 2 diabetics. Freeze-dried strawberries have also been found to decrease inflammation and improve glycemic control and antioxidant status in type 2 diabetics.
Safety: strawberries and their extract pose no safety concerns.
26 - 29. Dietary Fiber: Glucomannan, Inulin, Psyllium, Apple Fiber
Dietary fiber can be classified into two types: soluble and insoluble. Soluble fiber dissolves in water and forms a gel-like substance that can slow down the absorption of glucose and cholesterol, while insoluble fiber does not dissolve in water and adds bulk to the stool, which can prevent constipation and lower the risk of colon cancer.
According to a recent umbrella review of meta-analyses of randomized controlled trials, dietary fiber intake was associated with significant improvements in several cardiovascular risk factors, such as blood pressure, blood sugar, insulin resistance, and cholesterol levels. The review also found that the type of dietary fiber and the study population may influence the magnitude of the effects. For example, soluble fiber was more effective than insoluble fiber in lowering blood pressure and cholesterol, while insoluble fiber was more effective in reducing blood sugar and insulin resistance. Moreover, dietary fiber intake had greater benefits for people with diabetes or metabolic syndrome than for healthy individuals.
Another recent systematic review and meta-analysis of observational studies found that dietary fiber intake was inversely associated with the risk of metabolic syndrome, meaning that higher fiber intake was linked to lower odds of having the condition.
We use a mix of 4 different types of fiber for two reasons: each one works somewhat differently and by doing so we can reduce the quantity of each one and prevent unpleasant texture and flavor.
Safety: dietary fiber poses no health risk, except to those with Celiac, Crohn, UC, IBD, and similar. If you are one of those, please consult your doctor and you may also write to us to see what we can do for you.
i. Dietary Fiber and Metabolic Syndrome: A Meta-Analysis and Review of Related Mechanisms