Paradigm of Complementary and Alternative Medicine in Type 2 Diabetes

Abstract

Complementary and alternative medicine (CAM) is increasingly used by patients nowadays. The pooled prevalence of CAM use is about 51%. Many types of CAM have been practiced by patients with diabetes. Some of them showed promising results on blood glucose and other cardiometabolic parameters such as blood pressure, body mass, and lipid profile. This chapter explores two main types of CAM: Herbs and mind–body therapy. Different types of mind–body therapy and plants, plant extracts, and herbal substances have been utilized for an extended period and are sometimes favored by many individuals with T2D. Those practices and compounds found in these natural remedies are believed to have the potential to benefit the body in several ways, including the reduction of symptoms, alleviation of pain, and promotion of overall health. This chapter includes a summary of the findings of the available systematic reviews and meta-analyses regarding the most used medicinal herbs and body–mind therapies. In conclusion, as some of these interventions are promising, it is unclear to what extent glucose metabolism and certain substances can help mitigate complications in late-stage diabetes. Healthcare providers should be aware about them.

1. Introduction

Type 2 diabetes mellitus (T2D) is a chronic condition, where the body’s metabolic pathways for carbohydrates, proteins, and fat are disrupted due to various factors. These factors include defects in insulin secretion, reduced production of incretins in the gut, high levels of glucagon, increased production of glucose by the liver, issues with the endocrine function of adipose tissue, insulin resistance, increased activity of specific glucose transporter in the kidneys called sodium-glucose transporter-2 (SGLT2), and dysfunction in the hypothalamic centers that regulate hunger and fullness. All these lead to hyperglycemia, which carries risks to many organs of the human body [1]. The number of patients with T2D is expected to increase as long as there is no definitive treatment. It is expected to be around 578 million patients with T2D by 2030 and 700 million by 2045 worldwide [2].

Complementary and alternative medicine (CAM) has been defined as any healthcare practice that is not part of the nation’s standard medical care [3, 4, 5]. However, it is important to say there is no unified definition, and the terms “complementary” and “alternative” has been used interchangeably [5]. Each institute has its term and definition for such practices, for example, traditional or integrative medicine. The first terms used to describe unconventional medicine were “alternative” in 1975, “unconventional” in 1980, “complementary” in 1984, “complementary and alternative” in 1994, and “integrated/integrative” in 1995 [6]. CAM is widely spread and popular all over the world [3]. The pooled prevalence of CAM use is about 51%, with a wide range in prevalence between studies (8–93%) [7]. At present, traditional and complementary medicine (T&CM) has a user base of over 100 million in Europe. About one-fifth of these people use T&CM regularly, and the same amount of people prefer healthcare options that include T&CM. The number of united states adults using herbs and supplements went up from 38.2 million in 2002 to 40.6 million in 2012 [8]. Chinese medication was valued at approximately $83.1 in 2012. This was a 20% increase compared to the previous year [3]. According to research in Saudi Arabia, people typically spend about $560 per year from their own money on T&CM services [9].

Generally, patients with chronic diseases tend to use CAM because they are looking for any measure that could help to treat, control, or reduce the severity of their medical problems [10, 11]. According to the 2012 National Health Interview Survey and the Adult Alternative Medicine supplement, they collected the data of about 15 thousand patients who have one or more of the following diseases: hypertension, diabetes, hypercholesterolemia, or obesity. They found that 29.5% of the patients had used a CAM before [12]. The percentage of people who reported using T&CM (products and/or practitioners/therapies) in the past year ranged from 24 to 71.3% [13]. CAM is frequently utilized by a considerable percentage of individuals in Saudi Arabia, varying from a few to as many as 96%, who experience chronic mental and physical illnesses [14]. However, in Eastern Mediterranean countries members of the World Health Organization, the prevalence of CAM use among patients with T2D within the 14 countries ranged between 9 and 88.4% [15]. American diabetes association advised asking every patient with diabetes about any CAM use every visit [16].

There are some predictors to use CAM among patients such as affordability of the CAM, cultural beliefs, the cost of the healthcare services, loss of trust in healthcare workers and hospitals, and the belief in the importance and value of one’s inner life and experiences [3, 14, 17].

This chapter includes a summary of the findings of the available systematic reviews and meta-analyses regarding the most used medicinal herbs and body–mind therapies. It also includes suggestions for healthcare providers, stakeholders, and researchers in the field of CAM therapy in the management of type 2 diabetes.

2. Herbal medicine

Herbal medicine refers to the use of plants or plant extracts for their medicinal properties to promote healing and well-being. It is a traditional form of medicine that has been practiced for thousands of years in various cultures around the world. Herbal medicines often involve the use of leaves, flowers, stems, roots, or seeds of specific plants, which are prepared as teas, tinctures, capsules, or topical applications. These natural remedies are believed to contain bioactive compounds that can have therapeutic effects on the body such as reducing symptoms, alleviating pain, or supporting overall health. However, number of them have been studied, and their use is not strictly controlled, so it is hard to know what side effects they might have. This makes it difficult to figure out which therapies are the safest and most effective and to know how to prescribe such therapies [18]. One study was conducted on outpatients with chronic disease in Turkey and found that the level of adherence is affected by the use of herbal medicine [19]. About 7 out of 100 people had purchased natural herbal products online [20]. Although there is insufficient evidence to definitively confirm the effectiveness of specific herbs and supplements for diabetes, they generally appear to be safe [21]. Many herb consumers mistakenly believe that natural remedies are always safe and have no risks. However, some medicinal plants are toxic. Like all medicines, herbal remedies can have adverse side effects. Some of these side effects are caused by quality issues, such as the inclusion of undisclosed medications or potent pharmaceutical substances. Adverse events can also occur due to the incorrect use of herbal medicines, interactions with other medications, and the use of contaminated products. In the following sections, we will go through a review of the herbs used in T2D management.

2.1 Curcumin

Curcumin, also known as diferuloylmethane, is a natural substance found in the roots of the turmeric plant and other related plants. Curcuma longa is a plant that has been used as a medicine in Asia for a long time [22]. A randomized controlled trial was conducted to determine whether curcumin could help in diabetes prevention and found that after 9 months of curcumin intervention in prediabetic patients. The participants were asked to take six capsules of either curcumin or a placebo, each capsule containing a curcuminoid content of 250 mg. A significantly lower number of prediabetic individuals eventually developed T2D [23]. Another study on nano curcumin (as nano-micelle 80 mg/day) has found that it could help in reducing glycated hemoglobin (HbA1C), fasting plasma concentration (FPC), and 2-hour postprandial sugar (2hPP) in patients with T2D [24]. Combining Curcuma longa with hypoglycemic drugs, especially ones that are processed by the CYP2C19 and CYP2C9 enzymes and have a narrow therapeutic range, can alter their functionality within the body. Also, the combination can potentially interact in significant ways. However, additional research is needed to determine the advantages of using these things together [25].

In conclusion, Curcumin is one of the most extensively studied food-driven substances and is generally safe. The allowed daily intake is 0–3 mg/kg body mass. Curcumin might help in the prevention of diabetes complications; however, more studies are needed [26, 27, 28]. Moreover, it could help in reducing the non-high-density lipoprotein cholesterol (HDL-C) and lipoprotein(a) [Lp(a)] [29]. There are few side effects reported with higher doses such as diarrhea, skin rash, yellow stool, and an increase in serum alkaline phosphatase and lactate dehydrogenase [22].

2.2 Aloe vera

Aloe vera is a type of plant that belongs to the Asphodelaceae family. It is a type of plant that can survive in dry environments. For a long time, people in South Africa have been using traditional medicine, including Aloe vera to treat skin problems and other illnesses. This practice has been around for thousands of years [30]. Patients have used it for a long time to help lower plasma glucose concentration in people with diabetes or prediabetes. Some substances found in Aloe vera called chromium and alprogen can help fix damaged insulin cells in the pancreas, improve the working of insulin, and reduce high blood sugar levels [31].

A systematic review and meta-analysis was published in 2022 and included 642 patients, and found reduced FPC in patients with prediabetes and T2D. However, the sample size of the clinical trials was small in size, and most of the studies’ periods were short [31]. The previous clinical studies did not notice any negative herb-drug interaction [25].

There is still a need for more well-established and longer-duration studies. The patients need to consult with a healthcare provider before using Aloe vera as a supplement or adjunctive treatment for T2D.

2.3 Moringa oleifera

In the past, Moringa oleifera had been grown and consumed within its original regions. In the 1990s, some researchers began studying how it could be used to purify water. They later found out its nutritional and medical benefits, and now it is grown in almost all tropical and subtropical areas [32]. A systematic review covering the studies between 2008 and 2018 and found that moringa leaf powder intake showed statistical evidence of reduced plasma glucose concentration [33].

Moringa oleifera is not very safe because it has been found that there are certain compounds that can cause serious problems in the liver, kidneys, blood, and other parts of the body. Roasted Moringa oleifera seeds have substances that might lead to genotoxicity. The leaf contains a lot of saponins, which can be potentially harmful to vegetarians. These saponins can lower the amount of divalent and trivalent metals, such as zinc (Zn) and magnesium (Mg) that the body could absorb. Alkaloids in the tree’s root and bark, such as Spirochin and Benzothiocyanate, are toxic substances that are mostly present in the root and bark. As a result, the leaf was deemed the safest part to eat [34].

Moringa oleifera could help patients with diabetes when used with certain medications that are metabolized by CYP1A2 and CYP3A4 enzymes, such as pioglitazone. This combination can have a positive effect and allow for a lower dosage of antihyperglycemic medications [25]. There is still a need for well-constructed RCT to know the best way to prepare, use, and know the effect on plasma glucose concentration.

2.4 Fenugreek

Fenugreek (Trigonella foenum-graecum) is a plant found in various countries, with yellow flowers and pods containing seeds. The term “Trigonella” refers to its triangular flower shape, while “foenum-graecum” means Greek hay. It has been used in cooking and traditional medicine for a long time [35].

A recent systematic review of 14 clinical trial studies found a significant effect of fenugreek on HbA1c. However, the reduction in FPC and postprandial glucose (PPG) was not statistically significant [36]. A previous systematic review study found a significant effect of fenugreek on FPC, 2hPP, and HbA1c. Moreover, it concluded that the amount of fenugreek used was different for each person. Some participants used as little as 1 gram per day, while others used as much as 100 grams per day. The impact of using different amounts of fenugreek varied greatly. Studies using low doses of fenugreek (less than 5 g per day) showed no effects, while studies using a higher dose showed stronger effects [37]. The way the fenugreek supplement is made also affects how it affects glucose levels [37, 38]. As shown, using fenugreek for a long duration (180 days) does not add more benefit to blood glucose [38]. All the published systematic review papers addressed the heterogeneity and the problems in the quality of the clinical studies. There are a few side effects reported by the participants, such as abdominal pain and dyspepsia. However, all these symptoms subside after a 2-day withdrawal of fenugreek without any specific treatment [37]. More studies are required considering the fenugreek dose, as well as other factors that could affect the glucose level.

2.5 Urtica dioica (nettle)

Urtica dioica or stinging nettle is a plant that grows in many places around the world, including Asia, Europe, North Africa, and North America [39]. It is believed that it affects the glucose level through the induction of insulin secretion and proliferation of pancreatic B cells [40]. Ziaei et al. found that ingestion of Urtica dioica by patients with T2D reduced FPC but did not affect HbA1c or insulin levels [41]. One of the limitations of the systematic review by Ziaei et al. is the mode of preparation of Urtica dioica was varying between the studies. Moreover, all the studies were conducted in one country [41]. In another study, Tabrizi et al. found that Urtica dioica improved FPC, HbA1c, triglycerides, and SBP in patients with T2D [42]. There is limited scientific evidence regarding the specific effects of Urtica dioica (commonly known as stinging nettle) on type 2 diabetes. While some studies suggest that stinging nettle may exhibit antidiabetic properties, more research is needed to establish its effectiveness and determine the appropriate dosage.

2.6 Salvia officinalis

Salvia officinalis (Sage) is a plant that grows all over the world and has been used for a long time in cooking and medicine. It is also used in traditional medicine to help with different health problems such as seizures, ulcers, diarrhea, and inflammation [43]. Abdollahi et al. found that S. officinalis reduced 2hPP, FPC, and HbA1c in patients with T2D in a systematic review that included three studies only [44]. Overuse or excessive consumption of the ethanolic extract and volatile oil of S. officinalis can result in adverse effects on health. S.Officinalis can cause vomiting, excessive saliva, tachycardia, dizziness, hot flashes, allergic reactions, swelling of the tongue, bluish skin, and even seizures. Officinalis oil affects the nervous system directly, especially at doses higher than 0.5 grams per kilogram. Camphor, thujone, and terpene ketones are the most dangerous substances in Salvia oil. These substances might cause harm to the developing baby during pregnancy and after birth [43]. More studies are needed for longer durations to assess the effects on glycemic control considering the possible side effects of S. officinalis.

2.7 Sesamum indicum L. (sesame)

Sesame is a type of plant that produces seeds that people use to make oil. It is one of the oldest crops that humans have grown and eaten. In China, people have been using sesame seeds for over 5000 years. The biggest producers of sesame seeds are India, Sudan, Myanmar, China, and Tanzania. Tanzania has become the top producer in recent years, surpassing India. In 2017, the whole world produced about 5.9 million tons of sesame seeds, with Tanzania producing the most followed by China [45]. Ramírez-Coronel et al. and Sohouli et al. found that sesame help in reducing FPC and HbA1c significantly in patients with T2D [46, 47]. For people with certain health conditions, such as T2D and Metabolic syndrome, taking a certain amount of sesame oil or adding it to their food every day can help improve their health. They can have 30–35 ml of sesame oil each day or include it in their meals so that it makes up 30% of all the energy they get from food for 8–12 weeks. They can also take a supplement called sesamin, which is a special kind of sesame oil, by taking 200 mg of it every day for eight weeks [48].

2.8 Nigella sativa (black seed)

Nigella sativa, also known as black seed, that has been used for a long time in medicine. It comes from places such as Southern Europe, North Africa, and Southwest Asia. People have used the seeds and their oil to treat different sicknesses all around the world. It is even mentioned in religious texts as a special healing plant. People who follow the Islamic faith believe it is a very important medicine and should be used regularly [49]. It has been found that Nigella sativa improves FPC, HbA1c, total cholesterol, and LDL in patients with T2D [50, 51, 52]. When thymoquinone, Nigella sative derivative, was taken alongside metformin daily, it resulted in a more significant decrease in HbA1c and plasma glucose concentrations compared to taking metformin alone [53]. The effects of Nigella sativa on diabetes might be related to antioxidants and anti-inflammatory effects. It may also help in improving the levels of good cholesterol while reducing the levels of LDL and body mass [54].

2.9 Psyllium fiber (Isabgol)

Psyllium seeds, also known as Isabgol, come from the Plantago ovata plant and are highly valued for their nutrient-rich husk [55]. The first scientific article discussing psyllium was published in 1927, and since then, there have been over 1200 articles related to psyllium. Psyllium fiber was significantly reducing FPC, HbA1c, LDL, and triglyceride [56]. Dietary fibers in general significantly reduced TG, LDL, FPC, and HbA1c [57, 58]. A systematic review found that adding viscous fiber reduced HbA1c levels by 0.58% following a median dose of about 13.1 g/day over 8 weeks [58]. Individuals who have diabetes or are susceptible to diabetes should aim to consume a minimum of 14 grams of fiber per 1000 calories consumed. Half of the grains they eat should be whole grains. Eating enough fiber regularly can lower the risk of death for people with diabetes. Studies have shown that eating more fiber is also linked to a lower risk of getting type 2 diabetes [59].

2.10 Nopal

Nopal, which is also referred to as prickly pear cactus, has been proposed as having potential advantages for people diagnosed with (T2D). There are different types of Nopal, such as Opuntia streptacantha and Opuntia ficus-indica. Gouws et al. found no benefit for peaky fruit on glucose or insulin levels. However, the cladode exhibits potential glucose-lowering effects that are deserving further research and exploration [60]. The results of animal experiments demonstrated the potential of fruit extracts in the effective regulation of blood sugar levels [61].

Prickly pear seeds helped diabetic rats by increasing muscle and liver glycogen levels while also reducing plasma glucose concentration and increasing insulin sensitivity. It was observed in one study that the prickly pear cactus pad had led to a decrease in blood sugar levels in people with T2D on glipizide and metformin [62]. However, more studies are needed to confirm if using this herb together with standard diabetic medications is effective.

2.11 Astragalus membranaceus

Astragalus membranaceus, which is a member of the Fabaceae/Leguminosae family. The dried root of this plant is widely used and is recognized in both Chinese and Japanese pharmacopeia [55]. Tian et al. found that FPC, postprandial glucose, and HbA1c were significantly reduced after using Astragalus membranaceus in people with T2D [63]. One systematic review found a positive effect of Astragalus membranaceus on people with diabetic kidney disease [64]. Astragalus membranaceus has the ability to lower blood sugar levels by helping in increasing glucose transporter (GLUT4) in cells, preserving the function of beta cells, and increasing the release of insulin [65].

2.12 Momordica charantia (bitter gourd/bitter melon)

Momordica charantia, also known as bitter gourd or bitter melon, is a plant from the Cucurbitaceae family that is often utilized for its medicinal properties [66]. It helps in regulating the secretion of insulin and the synthesis of glycogen [25]. Momordica charantia was found to decrease FPC, PPG, and HbA1c significantly in people with T2D [67, 68]. No side effects were reported.

2.13 Olive oil

Olive oil is obtained from olives (Olea europaea, family Oleaceae). Mediterranean nations heavily rely on olive oil, which serves as a significant fat source. The quality of olive oil depends on various factors and processes involved in extracting it. During the time it is stored, it can additionally experience alterations before it is put to use [69]. Olive oil intake was associated with a significant reduction in FPC and HbA1c [70]. Increasing olive oil consumption by 25 grams per day was linked to a notable 22% decrease in the risk of developing T2D [71]. However, extra-virgin olive oil (EVOO) did not show any significant glycemic effect on people with T2D. However, animal studies showed a good hypoglycemic effect after EVOO use [72]. More RCT studies on EVOO with different doses are required to assess the hypoglycemic effect on people with T2D.

2.14 Allium sativum (garlic)

Garlic, Allium sativum, is a type of aromatic plant that is used in cooking. It was first found in places, such as Kazakhstan and China a long time ago, and people have been growing it ever since. Many different kinds of garlic can grow in different places around the world. Garlic was found to reduce the FPC and HbA1c significantly in people with diabetes [73, 74]. The inclusion of garlic in the diet had a notable impact on reducing HbA1c levels, and this effect was more pronounced among individuals who consumed garlic for a period of 24 weeks compared to those who consumed it for only 12 weeks [75]. Garlic was found to decrease blood pressure readings as well. Studies conducted on animals have provided evidence suggesting that aged garlic extract can inhibit the rise in plasma glycated albumin levels in mouse models with T2D. This beneficial effect is believed to be attributed, at least partially, to the activation of AMP-activated protein kinase, which subsequently leads to the suppression of both free fatty acid production and monocyte chemoattractant protein 1 (MCP1) gene expression in adipose tissue [76]. Garlic can help with common symptoms of diabetes such as polydipsia, polyuria, weight loss, and especially polyphagia. The consumption of garlic can regulate hunger and satiety, maintaining healthy energy levels of metabolism [77].

2.15 Zingiber officinale (ginger)

Ginger (Zingiber officinale) is a type of plant, that is, in the same family as other ginger plants. For hundreds of years, people have been using ginger to add flavor to their food and as a traditional medicine. We first learned about the medical use of ginger root in the sixth century BC. In the beginning, this plant was mostly used in countries, such as India and China. Over time, it started being sent to the Mediterranean region. The Greeks also used ginger to help with digestive problems [78]. Ginger reduced HbA1c and FPC significantly [79]. This was supported by previous studies that found that ginger could affect FPC, HbA1c, and lipid parameters positively [80, 81, 82]. No major differences in HbA1C levels were found in the trials when ginger was given as a supplement to research participants over the age of 50 [79]. Ginger aids in the management of diabetes by restoring the functionality of pancreatic β-cells and improving the utilization of glucose within the body. Other mechanisms involve enhancing the liver’s glycogen synthesis, promoting increased insulin release from the pancreas, and inhibiting the liver’s glucose production [25].

2.16 Panax spp. (ginseng)

Ginseng is a highly valued plant that can help treat many different illnesses. The ancient Chinese used ginseng in their medicine about 5000 years ago. Ginseng can be made from different types of Panax plants. These plants are used to make botanical preparations. There are 13 different types of ginseng, but the ones that are mostly used are Panax ginseng (also known as Korean ginseng) which is grown in China and Korea, and Panax quinquefolius (also known as American ginseng) which is grown in the United States and Canada. Multiple research studies have demonstrated the potential benefits of Panax ginseng and Panax quinquefolius with various health-related issues such as neurological, metabolic, infectious, and cancerous diseases [83].

One systematic review looked at the impact of taking a dose ranging from 200 mg to 8 g of Panax ginseng compared to a placebo, it found that the amount of blood glucose decreased by 1.77 mmol/L*hr. [84]. Another study showed that the ingestion of ginseng supplements for a duration of 8 weeks or more resulted in a significant improvement in fasting blood sugar (FSB) levels. However, the heart rate increased by about 2.65 beats per minute in patients taking ginseng compared to the control group [85]. No significant effect of ginseng on HbA1c level [84, 85, 86, 87]. Ginseng has been found in extensive research in vitro and on animal and human subjects to have the potential in regulating insulin levels, glucose absorption, and glucose processing in the body. It does this by preventing the death of beta cells and increasing the production of glucagon-like peptide-1 (GLP-1), which helps reduce the effects of diabetes [86].

2.17 Other herbs with promising effects on T2D

Cinnamon reduced FPC but did not affect HbA1c or insulin levels significantly [88, 89]. On the other side, Camellia sinensis, which belongs to the Camellia genus, is a type of plant that is used to make green and other types of tea, where assessed by Wang et al. found a statistically significant reduction of FPC and HbA1c in people with T2D by Camellia sinensis use [90, 91]. These findings are contradicting previous studies that failed to show any benefit on blood glucose in people with T2D [92, 93]. The studies are still inconclusive and advise for more well-organized RCT to assess the green tee effectiveness. Another plant called Coccinia grandis belongs to the Cucurbitaceae family, which includes 960 different species. This herb was assessed by a double-blind RCT. The patients were advised to take 20 g of leaves of Coccinia grandis with the breakfast. It found that the postprandial glucose was significantly reduced compared to the control group [94]. The need for more RCT is required to prove the effect of this plant.

2.18 Common herbs with no significant effect on blood glucose levels

2.18.1 Ginkgo Biloba

Ginkgo biloba L. is a valuable source for developing new herbal medicines, also known as the maidenhair tree. It is a living fossil that has impressed scientists worldwide due to its abundance of bioactive compounds and medicinal value. This type of species is commonly used to treat some central nervous system diseases, such as Alzheimer’s disease and memory problems. The Ginkgo tree is grown a lot in many countries such as Asia, Europe, North America, New Zealand, and Argentina. This tree has been used in Chinese medicine for a very long time, around 2000 years. Many people use Ginkgo leaf extracts in herbal medicine, food supplements, and natural remedies [95]. Ginkgo biloba was found to increase HbA1c levels in people with T2D [96]. However, the extract from the Ginkgo biloba tree reduced the amount of albumin in urine, lowered the fasting blood sugar levels, and decreased levels of creatinine, blood urea, and nitrogen [97]. Moreover, it might help in treating diabetic retinopathy alongside conventional medicine [98]. More studies are required to assess the effect of Ginkgo biloba on plasma glucose concentration.

2.18.2 Walnut

It has been found by two systematic review studies that the consumption of walnuts did not significantly impact fasting blood sugar levels or HbA1c. That means the positive effect of walnut on the cardiovascular system is not related to the improvement of blood sugar levels. The current evidence has a high risk of bias, so we need more randomized well-conducted clinical trials to get reliable results on the walnut effect on blood sugar [99, 100]. Moreover, the walnut increased leptin and adiponectin levels but does not affect the body mass of people with T2D [101, 102].

2.18.3 Capsicum frutescens or annuum

Pepper, also known as Capsicum, is a widely cultivated crop with a long history of use. It originated in America and there are over 200 species of pepper, each with different tastes and levels of heat. Pepper is commonly used as a condiment or food ingredient and has various medicinal uses in Indian, American, and Chinese traditions. It belongs to the Solanaceae family and is highly valued for its spiciness and flavor [103]. A systematic review and meta-analysis study found no effect of Capsicum annuum on plasma glucose concentration. However, the number of the studies is small with high heterogeneity [104]. Moreover, studies have shown that using capsaicin cream with a low concentration of 0.075% can help reduce pain in people with diabetic neuropathy. This cream can be applied to painful areas for around 8 weeks. It is well tolerated by patients and is effective in improving pain levels, mobility, ability to work and sleep, and participation in recreational activities. Similarly, giving a higher amount of topical capsaicin, specifically 8%, also works well in reducing pain for people with diabetic neuropathy [105].

2.18.4 Homeopathy

Homeopathic medicine follows two main ideas. First, the principle of similarity says that something that causes a problem can also cure it. Second, it believes that the more diluted a substance is, the stronger its healing power becomes. However, these ideas have not been proven and go against what doctors and scientists know about medicine [106]. The prevalence of using homeopathy in adults over the last 12 months across 11 countries is between 0.2–8.2% for the period 1990–2012 [107]. A systematic review tried to assess homeopathy in people with T2D and no studies were found comparing homeopathic remedies to either a placebo or an active drug for treating diabetes or obesity [108].

One study tried to track the case reports and series that are related to the adverse effects of homeopathy. It found that there are about 1159 patients who experienced direct or indirect adverse effects of homeopathy. The direct adverse effects of homeopathy use lead to serious outcomes such as cancer, death, dialysis, toxic polyneuropathy, and quadriparesis. Indirect adverse effects included deterioration of pulmonary allergy, hypertensive heart failure, encephalopathy, and others. Most cases of adverse effects in homeopathy are caused by allergic reactions or ingestion of toxic substances. Heavy metals, such as arsenic, cadmium, mercury, and iron, commonly used in homeopathy, can be toxic if not properly diluted. Other poisons used in homeopathy, such as aconitum, kerosene, or thallium, can also pose serious health risks if not adequately diluted [109].

The National Health and Medical Research Council (NHMRC) in Australia has determined that there is no reliable evidence to support the effectiveness of homeopathy in treating any health conditions. Therefore, it is not recommended to use homeopathy for chronic, serious, or potentially serious conditions. People who rely solely on homeopathy may jeopardize their health by rejecting or delaying treatments that have been proven safe and effective [110].

3. Conclusion regarding the medicinal herbs

Some herbs, such as Sesame, Aloe vera leaf gel, Psyllium fiber, and Fenugreek seeds demonstrated a significant impact on the levels of HbA1c compared to other studied herbs. Other herbs decreased HbA1c by at least 0.5%, such as Nigella sativa and Astragalus membranaceus. Some herbal remedies had not been assessed by a meta-analysis [111].

Traditional dietary and lifestyle recommendations for people with diabetes rarely include information on natural remedies, herbs, and spices that can help control blood sugar levels. However, this review guides patients interested in using herbal supplements and foods as part of their self-care and diet, as well as clinicians consulting them. Some of the tested remedies are both effective and safe, and many of these herbs and spices are commonly used in food and considered very safe. Some can easily be incorporated into the diet, while others can be purchased without a prescription. However, it is important to ensure that the most effective preparations are used in adequate dosages. Additionally, it is important to inform patients and clinicians about remedies that are ineffective or lack sufficient evidence of effectiveness [111].

Regarding the clinical trials on the herbs, the discussion is focused on how both environmental and individual factors can influence the outcomes achieved. It is difficult to determine whether the results are due to natural treatments or accompanying medicines. Unhealthy habits, such as a poor diet, can have negative consequences when using natural products. Each patient’s unique qualities, including lifestyle, genetics, existing health issues, and previous treatments, can lead to different outcomes. Therefore, it is important to consider these personal characteristics when conducting such studies. Most of the trials encountered a couple of issues. An obstacle is presented by the differences among the clinical trial participants. Furthermore, the trials’ poor design has resulted in different results for different individuals. Moreover, both the inadequate number of participants and brief durations characterize these trials. Additionally, the limited amount of data available can impact the application of the results to a larger population or special population, such as pregnant ladies or patients with diminished renal or liver functions [112, 113]. The summary for all systematic reviews and meta-analysis regarding medicinal herbs are shown in Table 1.

Study’s First author	Herb	No. of included studies/patients	Study period	The main findings	The effect on glucose level
Budiastutik et al. [31]	Aloe vera	13 / 642	2011–2021	Aloe vera reduced FBS significantly. There is high heterogeneity between the included clinical trial	FBG: (−1.238 mg/dl, 95% Cl: −1.853, −0.623)
Owens et al. [33]	Moringa oleifera	30 / 158	May 1, 2008 - May 1, 2018	Moringa significantly decreased blood glucose levels In some cases, increased insulin levels in diabetic patients.	It is a systematic review paper, not a meta-analysis
Shabil et al. [36]	Fenugreek	14 / 894	Up to November 18, 2022	There is a reduction in FBS, and PPG, but was not statistically significant. There is a statistically significant reduction in HbA1c There is high heterogeneity between the included studies	FBS: (MD: 3.70, 95% CI of −27.02, 19.62); PPG: (MD: −10.61, 95% CI of −68.48, 47.26); HbA1c (MD: −0.88, 95% CI −1.49, −0.27)
Neelakantan et al. [37]	Fenugreek	10 / 278	up to 29 Nov 2013	significant reduction in FBS, 2-hr glucose, and HbA1c. There was a large variation between the included studies in the dose of fenugreek seeds used ranging from 1 g per day to 100 g/day. The quality of the included clinical trials was generally poor	FBS: (−0.96 mmol/l (95% CI: −1.52, −0.40); 2-hPP: (−2.19 mmol/l (95% CI: −3.19, −1.19); HbA1c: (−0.85% (95% CI: −1.49%, −0.22%)
Khodamoradi et al. [38]	Fenugreek	12 / 823	2000 to 31 July 2019	Fenugreek reduces FBS, LDL-C, and HbA1c levels significantly. Fenugreek did not affect BMI	FBS: (−12.94 mg/dL, 95%CI: −21.39, −4.49); HbA1c: (−0.58%, 95% CI: −0.99, −0.17%)
Ziaei et al. [41]	Urtica dioica	8 / 266	2012 and 2017	Effective in reducing FBS No effect on HbA1C or insulin level	FBS [WMD]: (−18.01 mg/dl, 95% CI: −30.04 to −5.97); HbA1c: [WMD]: (−0.77%, 95% CI: −1.77 to 0.22)
Tabrizi et al. [42]	Urtica dioica	13 studies	Up to December 2019	improvement in levels of FBS, HbA1c, CRP, triglycerides, and SBP No significant change in serum levels of insulin, TC, LDL-C, HDL-C, BMI, and diastolic blood pressure (DBP)	FBG [WMD]: (− 17.17 mg/dl, 95% CI: −26.60, −7.73); HbA1c [WMD]: (−0.93, 95% CI: - 1.66, −0.17)
Abdollahi et al. [44]	Salvia officinalis	3 / 85	Up to March 2021	Salvia officinalis reduced 2hPP, HbA1c, TC, LDL. No significant effect on TG, and HDL. No specific side effects were reported	FBS [MD]: (−31.15 mg/dL; 95% CI: −37.56 to −24.73); HbA1c [MD]: (−0.94%; 95% CI: −1.25 to −0.63)
Ramírez-Coronel et al. [46]	Sesamum indicum L.	8 / 395	Up to December 2022	Sesame consumption significantly reduced serum FBS and HbA1c percentage in patients with T2D	FBS [WMD]: (−28.61 mg/dL, 95% CI: −36.07 to −21.16); HbA1C [WMD]: (−0.99%, 95% CI: −1.22 to −0.76)
Sohouli et al. [47]	Sesamum indicum L.	8 / 510	Up to February 2021	Sesame consumption significantly reduced serum FBS and HbA1c percentage in patients with T2D	FBG [WMD]: (−21.31 mg/dl, 95% CI: −41.23, −1.39); HbA1c [WMD]: (−0.75, 95% CI: −1.16, −0.34)
Khotbehsara et al. [50]	Nigella sativa	7 / 255	Up to February 2017	Significantly improved FBS, HbA1c, TC and LDL The overall effects of TG and HDL-c were insignificant	FBS: (−17.84 mg/dl, 95% CI: −21.19 to −14.49); HbA1c: (−0.71%, 95% CI: −1.04, −0.39)
Hamdan et al. [51]	Nigella sativa	7 / 447	2009 and 2015	Concluded that there is Improvement of FBS, 2hPP, HbA1c, insulin level and insulin resistance	It is a systematic review paper, not a meta-analysis
Hallajzadeh et al. [52]	Nigella sativa	50 / 3679	Up to October 30, 2019	Significantly reduced FBS, HbA1c, TG, TC, VLDL, LDL.; No effect on insulin level or insulin resistance	FBS [WMD]: (−15.18 mg/dl; 95% CI: −19.82, −10.55); HbA1C [WMD]: (−0.45%; 95% CI: −0.66, −0.23)
Mahomoodally et al. [53]	Nigella sativa	17 / 3679	Up to January 2022	Concluded that there is improvement of FBG, PPBG, HbA1c, HOMA-IR, and HOMA-β	It is a systematic review paper, not a meta-analysis
Xiao et al. [56]	Psyllium fiber	8 / 395	from 1998 to August 2019	Significant reduction in TG, LDL, FBS, and HbA1c using about 10 g/day No significant change in weight No side effects were reported	HbA1c [MD]: (−0.91%, 95% CI −1.31, −0.51); FBS [MD]: (−31.71 ml/dl, 95% CI −50.04, −13.38)
Ting Mao et al. [57]	Dietary fiber	22 / 911	Up to March 23, 2021	Significant reduction in FBS, HbA1c, fasting insulin, and HOMA-IR using about 10 g/day No significant effect on BMI	FBS [WMD]: (−0.80 mmol/L, 95% CI −1.14, −0.46); HbA1c: (−0.66%, 95% CI −0.94, −0.38)
Jovanovski et al. [58]	Viscous fiber including psyllium	28 /1394	Up to 15 June 2018	Significant reduction in FBS, HbA1c, and HOMA-IR HbA1c levels were reduced by 0.58% following a median dose of about 13.1 g/day over 8 weeks	HbA1c [MD]: (−0.58% [95% CI −0.88, −0.28); FBS [MD]: (−0.82 mmol/L, 95% CI −1.32, −0.31)
Gouws et al. [60]	Opuntia spp. cacti	20 / 450	Up to September 2018	Prickly Pear fruit was predominately reported to have no significant effects on glucose or insulin. The cladode does however show promise in potential glucose-lowering effects which warrant further investigation	It is a systematic review paper, not a meta-analysis
Tian et al. [63]	Astragalus membranaceus	13 / 1054	Up to December 2015	reduced FBS, PPG, and HbA1C no adverse reactions were reported	FBS [WMD]: (−0.28, 95% CI −0.46 to −0.10); PPG [WMD]: (−0.47, 95% CI −0.77 to −0.17); HbA1c [WMD]: (−1.77, 95% CI −3.06 to −0.47)
Peter et al. [67]	Momordica charantia	10 / 1045	1st January 1960–30th April 2018	reduced significantly FBS, PPG, and HbA1C There is an overall moderate to high risk of bias No serious adverse effects were reported	FBS [MD]: (− 0.72 mmol/L, 95% CI: −1.33, −0.12); PPG [MD]: (− 1.43 mmol/L, 95% CI: −2.18, −0.67); HbA1c [MD]:(− 0.26%, 95% CI: −0.49, −0.03)
Phimarn et al. [68]	Momordica charantia	8 / 507	Up to June 2016	Significant reduction in FBS, HbA1C, LDL-C, TC, TG, and body weight	FBS [WMD]: (−25.03 mg/dL; 95% CI −41.17, −8.89); HbA1c [WMD]: (−0.20%; 95% CI −0.36, −0.04)
Schwingshackl et al. [70]	Olive oil	33 / 187,068	Up to August 2016	Olive oil reduced HbA1c and FBS significantly; It is associated with a 16% risk reduction of T2D	HbA1c [MD]: (−0.27%; 95% CI: −0.37, −0.17); FBS [MD]: (−0.44 mmol l − 1; 95% CI −0.66, −0.22)
Dehghani et al. [72]	Olive oil	13 / 633	Up to 1 September 2020	Extra-virgin olive oil did not show any effect on blood glucose	FBS [SMD]: (−0.07; 95% CI: −0.20, −0.07)
Shabani et al. [73]	Allium sativum (Garlic)	33 / 1273	1988 and 2016	Garlic reduced HbA1c, FBS, TC, LDL, and TG. Moderate risk of publication bias may exist in HbA1c.	FBS: (10.90 mg/dl, 95% CI, −16.40, −5.40); HbA1c: (0.60 mg/dl, 95% CI, −0.98, −0.22)
Wang et al. [74]	Allium sativum (Garlic)	9 / 768	up to April 2017	Significant improvement of FBS, HbA1c and fructosamine Improved TC and LDL	After 24 weeks: FBS [SMD]: (−21.02, 95%CI −32.47, −9.57); HbA1c [SMD] = (−13.25, 95%CI −15.83, −10.68)
Ebrahimzadeh et al. [79]	Zingiber officinale (Ginger)	10 / 597	2013 - September 2021	Significant reduction in FBS and HbA1c; Significant effect on SBP and DBP; No significant effect on lipid profile	FBS (WMD) = (− 18.81; 95% CI: − 28.70, − 8.92); HbA1C (WMD) = (−0.57; 95% CI: −0.93, −0.20)
Jafarnejad et al. [80]	Zingiber officinale (Ginger)	9 studies	up to 30 October 2016	Reduced FBG, TG, and TC and significantly increased HDL-C No serious side effects	FBS (WMD) = (−14.93; 95% CI: −19.83 to −10.04)
Zhu et al. [82]	Zingiber officinale (Ginger)	10 / 608	Up to May 19, 2017	Significant reduction of HbA1c. FBS and fasting insulin Positive significant effect on TG, TC, LDL, and HDL No serious side effect	HbA1c [MD]: (−1.00, (95% CI: −1.56, −0.44); FBS [MD]: (−21.24; 95% CI: −33.21, −9.26)
Fy Huang et al. [81]	Zingiber officinale (Ginger)	8 / 454	Up to July 2018	No significant effect of FBS Significant reduction of HbA1c	FBS [WMD]: −0.27, 95% CI: (−5.09–4.54); HbA1c [WMD]: (−0.46, 95% CI: 0.09–0.84)
Park et al. [84]	Panax quinquefolius; (Ginseng)	23 /224	Up to September 2020	No significant improvement in FBS, HbA1c, and 2hpp Statistically significant effect on TC, TG, and LDL Improvement of blood pressure	FBS [AUC]: −1.77 mmol/L*hr.; (95% CI: −2.97 to −0.57)
Naseri et al. [85]	Panax quinquefolius; (Ginseng)	20 /1295	Up to 10 April 2022	Significant reduction of FBS, HOMA-IR, and TC. No significant effect on OGTT, HbA1,c, TG and BMI	FBS [WMD]:(−7.03 mg/dL; 95% CI: −10.89, −3.17)
Gui et al. [114]	Panax quinquefolius; (Ginseng)	8 / 90	Up to March 2, 2015	No significant effect on HbA1c, FBS or postprandial glucose	HbA1c: std. diff in means:  (−0.148, 95% CI: −0.637 to 0.228); FBS, std. diff in means: (−0.306, 95% CI: −0.539 to −0.074)
Shishtar et al. [87]	Panax quinquefolius (Ginseng)	16 / 770	Up to July 3, 2013	Significant effect on FBS No significant effect on HbA1c, or postprandial glucose	FBS: MD  =  (−0.31 mmol/L [95% CI: −0.59 to −0.03])
Namazi et al. [88]	Cinnamomum verum	18 studies	Up to 31 February 2018	Significant reduction of FBS No statistically significant reduction in HbA1c, insulin levels, waist circumference, and BMI.	FBS: (−19.26 mg/dL, 95% CI: −28.08, −10.45); HbA1C (−0.24%; 95% CI: −0.48, −0.01; I2: 76.8%)
Wang. [91]	Camellia sinensis	16 / 832	up to January 30, 2021	Statistically significant reduction of FBS, HbA1c, and TG No positive effect on LDL The tea preparations were different between the studies. No serious adverse events were reported	FBS [MD]: (−0.50 mmol/L 95%CI, −0.99, −0.01); HbA1c [MD]: (−0.37%, 95%CI -0.47, −0.26)
Yu. [93]	Camellia sinensis	6 / 382	up to April 2017	No significant effect on fasting insulin, FBS, or HbA1C The included studies are small	HbA1c [SMD]: (−0.32; 95% CI –0.86 to 0.23); FBS [SMD]: (−0.10; 95% CI, −0.50 to 0.30)
Tabrizi et al. [96]	Ginkgo biloba	7 / 768	Up to September 2, 2019	Ginkgo biloba can significantly improve HDL-cholesterol levels; however, it increases HbA1c levels.	HbA1c [WMD]: (−0.26, 95% CI -0.02, −0.50); FBS [WMD]: (−4.15, 95% CI −8.99, 0.70)
Mateș et al. [99]	Walnut	17 / 871	Up to November 2021	statistically significant decreasing effects for triglyceride, total cholesterol, and LDL cholesterol concentrations No consequences on anthropometric or glycemic parameters.	FBS [SMD]: (−0.01; 95% CI: 0–0.02); HbA1c [SMD]: (0.08; 95% CI: −0.04–0.2)
Neale et al. [100]	Walnut	16 / 1283	Up to 2 March 2019	No positive effect on blood sugar levels	FBS [WMD]: (−0·331 mg/ dl; 95% CI −0·817, 1·479); HbA1c [WMD]: (−0.03, 95% cl −0.00,0.06)
Jang et al. [104]	Capsicum annuum	3 studies	up to April 2020	BMI reduced but not statistically significant No effect on blood glucose TC, or BP Had a significant effect on LDL	Blood glucose [SMD]: (− 0.58; 95% CI − 1.62, 0.45)

Table 1.

Summary of systematic review and meta-analysis papers of the studied herbs.

FBS: fasting blood sugar, PPG: postprandial glucose, HbA1c: glycated hemoglobin, MD: mean difference, WMD: Weighted mean difference, HDL: high-density lipoprotein, LDL: low-density lipoprotein, VLDL: very low-density lipoprotein, TC: total cholesterol, TG: triglyceride, BMI: body mass index, 2hPP: 2-hour postprandial, BP: blood pressure. HOMA-IR: Homeostatic Model Assessment for Insulin Resistance, SMD: standardized mean differences. AUC: area under the curve.

4. Mind-body therapies

4.1 Yoga

Yoga is a type of exercise that focuses on both body and mind. It requires both physical movement and mindful focus on one’s thoughts, feelings, breathing, and energy [115]. One systematic review and meta-analysis published in 2022, tried to assess whether yoga training could affect diabetes-related indicators compared to usual care. It included 13 studies with a sample size of 1335 people with T2D. The study found a significant effect of yoga on HbA1c, FPC, PPBG, and TG. In the coming years, it is recommended to undertake extensive studies involving a higher number of participants to examine the prolonged effects of yoga on individuals diagnosed with T2D [116]. These findings are similar to previous systemic reviews, which were published in 2010 and 2016 and found that positive effect of yoga on HbA1c and FPC. However, the risk of bias and heterogeneity among the included studies is high [117, 118].

4.2 Meditation

Meditation involves engagement in activities that promote relaxation and contentment for the mind and body. It helps people feel better overall. Meditation usually involves focusing on breathing, feeling relaxed, staying focused, and being mindful of the thoughts and body at the same time. A survey reveals that the number of American adults who engaged in meditation with mantras, mindfulness, or for spiritual motives had tripled between 2012 and 2017. It went from 4.1 to 14.2% [119]. One systematic review and meta-analysis study was conducted to assess the effects of meditation interventions on the self-management of people with T2D. It found that mindfulness-based meditation reduced hemoglobin A1c levels but not fasting blood sugar levels [120]. There were problems with the randomization in some studies and with missing information about the results. Variations in the duration of follow-up, group size, and measured outcomes were prominent among the included studies [120].

4.3 Hydrotherapy

Hydrotherapy means using water as medicine to improve health. It involves using hot or cold water and sometimes adding minerals or herbs to directly affect the flow of blood and hormones in the body, which helps alleviate symptoms of certain illnesses [121]. Hydrotherapy was found to have a positive effect on high blood sugar as shown in a systematic review study [122]. The patients need to be cautious about the water temperature since patients with neuropathy may not have the ability to perceive if they are burning themselves. When recommending hot-tub therapy to people with diabetes, it is important to treat the water properly and give them the right instructions [123].

4.4 Muscle relaxation

Progressive muscle relaxation (PMR) was tried by quasi-experiment with pre-and posttest randomized control study. The study involved 48 inpatients with high plasma sugar concentration. The people in the study practiced relaxation exercises two times a day for three days in a row. Each session lasted about 25 to 30 minutes. Participants in the control group engaged in breathing exercises. There were big differences in the average plasma sugar levels of T2D people who received treatment compared to the other group [124]. PMR and mindfulness meditation were found to alleviate diabetic neuropathy in people with T2D [125].

4.5 Acupuncture

A systematic review showed a positive effect of acupuncture on plasma glucose concentration and HbA1C. However, most of these studies were conducted in China, and some of them have a bias in the methodology [126]. Other systematic review research showed that acupuncture, when used alongside medication for diabetes, can slightly but statistically significantly help in lowering fasting plasma glucose concentration and improving insulin resistance. The effects of acupuncture on HbA1c, 2hBG, and fasting insulin levels were uncertain [127]. One study reviewed the side effects on 229,230 patients who received on average 10.2 ± 3.0 acupuncture treatments. It found that 19,726 patients (8.6%) had at least one adverse effect and 4963 (2.2%) reported one which required treatment. The most commonly reported side effects were hematoma or bleeding [128].

Acupuncture is generally considered safe for individuals who have mild diabetes and should be performed by trained specialists to minimize the side effects. However, there is still a need for more well-conducted clinical trials to show how acupuncture affects T2D either in the short or long term.

4.6 Therapeutic massage

Therapeutic massage aims to enhance overall well-being by gently manipulating and stroking the body’s soft tissues, to facilitate relaxation and improve sleep quality. It can also help with specific issues, such as reducing muscle pains or discomfort. Most cultures have created ways to use therapeutic massage. Massage methods are significant in traditional Chinese and Indian healthcare [129]. There are different types and techniques of massage therapy such as Swedish, tactile, and compressed air. Bayat et al. found that therapeutic massage could decrease FBS and HbA1c. Also, it could help in improving neuropathic pain in patients with diabetic neuropathy [130].

4.7 Tai chi

Tai chi sessions involve various physical movements, such as slow, flowing motions resembling a dance. It can also include sitting or standing meditation postures and gentle or vigorous body shaking. The focus is on deliberately controlling both breath and thoughts while coordinating with the body’s movements [131].

A meta-analysis showed that doing tai chi for 4000–5999 minutes can help improve blood sugar and HbA1c levels for people with type 2 diabetes. Doing tai chi exercise for 80–120 minutes each week for over a year, or 160–240 minutes each week for over six months, can help control their blood sugar and HbA1c levels. The recommended quantity of tai chi exercise aligns with the amount of moderate-intensity exercise suggested in the clinical practice guidelines, which is around 150 minutes weekly [132]. Moreover, practicing tai chi could help people with T2D to reduce triglyceride, improve HDL-C cholesterol, lower their BMI, and improve their quality of life [133, 134, 135].

4.8 Moxibustion

Moxibustion is a traditional treatment method that has been used in Eastern Asian countries for thousands of years to alleviate various ailments, with a particular focus on pain conditions. This therapy involves stimulating specific acupuncture points on the body using dried Mugwort leaves, which are burned and applied directly or indirectly to the skin. In a study conducted by Kim et al. the effectiveness of moxibustion in the treatment of T2D was investigated. However, the researchers faced challenges in drawing definitive conclusions about the efficacy of moxibustion for controlling T2D due to the limited number of trials available and the overall poor quality of the included studies [136].

4.9 Conclusion regarding the mind-body therapies

Mind–body interventions encompass various practices and methods that promote the integration of the mind, body, thoughts, and actions to enhance physical well-being and overall health. Practices, such as yoga, meditation, and tai chi, have been found to improve glycemic control, reduce stress, and enhance overall well-being in individuals with T2D. Based on all the above-mentioned studies, it seems like we need more research studies in the field of T2D treatment to determine if using (CAM), including mind–body therapies, on a regular basis is effective and safe. These studies should have to include a large number of participants and reliable data to make strong conclusions. Experienced experts are in a great position to create, carry out, and explain integrative research for common use. The summary for all systematic reviews and meta-analysis regarding mind–body therapies are shown in Table 2.

Study’s First author	CAM modality	No. of included studies/patients	Study period	The finding
Chen et al. [116]	Yoga	13 / 1335	Up to July 2021	Good and significant effect on FBS, HbA1c, and TG No effect on TC or BMI
Aljasir et al. [117]	Yoga	5 / 362	Up to May 2007	Good effect on FBS, and lipid profile Reduction of Hb1c and BMI but was not significant in the trials. No calculated pooled effect because of the high level of heterogeneity between the characteristics of the studies
Kumar et al. [118]	Yoga	17 / 1521	Up to December 17, 2014	Good effect of yoga as an additional intervention to the treatment Good effect on FBS and HbA1c risk of bias was overall high
Heo et al. [120]	Meditation	9 / 698	Up to March 2022	Improved hemoglobin A1c but not fasting blood glucose
Yogapriya Chidambaram et al. [122]	Hydrotherapy	6 studies	Up to December 20, 2022	Hydrotherapy is effective in reducing blood sugar level Two studies used hot treatments, two used cold treatments, and two used both ht and cold treatments.
Chen et al. [126]	Acupuncture	21 / 1943	2001 - June 4, 2018	Acupuncture plus baseline treatments yield a reduction in FBG, 2hPP, and HbA1c. There are many pitfalls in the method of the involved clinical trials.
Qing et al. [127]	Acupuncture	21 / 1188	Up to July 5, 2020	Improved fasting blood glucose and insulin resistance. No clear improvement in HbA1c or 2hPP levels
Bayat et al. [130]	Massage	12 /581	January 1, 2000 - May 13, 2018	Statistically significant improvement in FBS, and HbA1c Improvement in neuropathic pain Low sample size of the RCTs
Chao et al. [132]	Tai chi	14 / 798	Up to June 2016	Tai chi reduces FBS and HbA1c The quality of included papers was low
Xinzheng et al. [133]	Tai chi	18 / 1220	2008 and 2020	Tai Chi exercise therapy shows significant superiority in improving the FBG, HbA1c, TG, and HDL-C
Cai et al. [135]	Tai chi	24 / 1314	Up to December 2021	Tai Chi improved HbA1c, FBG, fasting insulin, DBP, BMI, and the quality of life (QoL) in patients with T2DM. There was no difference between Tai Chi and other exercise types in the HbA1c, FBG, TC, TG, HDL, LDL, BMI, and (WC).

Table 2.

Summary of systematic review and meta-analysis papers of the studied mind–body therapies.

FBS: fasting blood sugar, PPG: postprandial glucose, HbA1c: glycated hemoglobin,, HDL: high-density lipoprotein, LDL: low-density lipoprotein, VLDL: very low-density lipoprotein, TC: total cholesterol, TG: triglyceride, BMI: body mass index, 2hPP: 2-hour postprandial, BP: blood pressure DBP: diastolic blood pressure. WC: waist circumference.

5. Suggested actions for stakeholders and healthcare providers

World health organization published a guideline entitled “WHO guidelines on safety monitoring of herbal medicines in pharmacovigilance systems” and encouraged the national health supervision centers to keep people safe when using herbal medicines by application of the followings:

1. Recognizing the adverse events has occurred.

2. Management of the risks.

3. Putting rules and regulations in place to prevent the adverse events.

4. Explaining clearly the advantages and risks of herbal remedies in an easy-to-understand manner.

WHO published another strategy named (WHO traditional medicine strategy 2014–2023) to face the challenges facing traditional and complementary medicine T&CM. This strategy includes [3]:

1. build the knowledge base that will allow T&CM to be managed actively through appropriate national policies that understand and recognize the role and potential of T&CM.

2. strengthen the quality assurance, safety, proper use, and effectiveness of T&CM by regulating products, practices, and practitioners through T&CM education and training, skills development, services, and therapies.

3. promote universal health coverage by integrating T&CM services into health service delivery and self-health care by capitalizing on their potential contribution to improve health services and health outcomes, and by ensuring users are able to make informed choices about self-health care.

Moreover, Healthcare providers need to be aware of the reliability and accuracy of online information regarding CAM treatments for T2D. In over half (56%) of the websites surveyed, the sources utilized for information gathering were deemed unreliable [137]. Healthcare providers need to communicate with their patients about the various treatment options. They also should understand how their patients search for information and direct them to reliable resources for health information. Furthermore, researchers, healthcare providers, and educators must establish guidelines addressing emerging and significant concerns associated with online health information. They should also be aware people about the false information on the internet and social media and help patients find trustworthy online sources.