In the context of Advanced Precision Nutrition, I would like to highlight how crucial the specificity of nutraceutical indications is in clinical practice.
In particular, in the case of turmeric (root or dry extract) compared to BIOCURCUMIN (a nanoemulsified curcumin formulation) I would like to highlight the great difference and effectiveness based on the specific context.
Turmeric, both in its natural root form and as a full-spectrum dry extract, can be a valid alternative when aiming to obtain an indirect systemic effect, acting through the modulation of the microbiota and the related formation of anti-inflammatory substances, therefore as a prevention-oriented choice.
On the other hand, when the objective requires a more targeted and acute approach, biocurcumin, a molecular form much more bioavailable and a longer half-life thanks to its nanoemulsions, may be the most suitable choice. Especially when greater safety is desired with respect to possible drug-nutraceutical interactions on cytochromes P450.
In this article, we would like to focus on the effectiveness of various forms of turmeric or its active ingredient called curcumin, in diabetes mellitus.
Meta-analysis summary
Diabetes mellitus (DM) comprises a number of metabolic conditions that have reached epidemic proportions worldwide. The complexity of the disease, influenced by multiple factors, makes patient management, including the need for long-term drug therapy and lifestyle modifications, a considerable challenge. In recent times, there is growing evidence suggesting the effectiveness of using plant or herbal supplements for the prevention and control of DM.
Curcumin is a bioactive compound extracted from Curcuma longa and is known for its multiple physiological and pharmacological properties, including antioxidant, anti-inflammatory, anticancer, neuroprotective, and antidiabetic activities. Therefore, we will analyze a systematic review of the effects of Curcuma longa and curcumin on diabetes mellitus. The search was conducted using databases such as PUBMED and EMBASE, and finally, sixteen studies were selected that met the inclusion criteria.
The results revealed that the antidiabetic efficacy of curcumin could be derived from its ability to reduce oxidative stress and the inflammatory process. In addition, curcumin was found to significantly reduce fasting blood glucose, glycated hemoglobin, and body mass index. In addition, the use of nanocurcumin was associated with a significant decrease in the levels of triglycerides, VLDL cholesterol, total cholesterol, LDL cholesterol, HDL, serum C-reactive protein, and plasma malonaldehyde .
Consequently, curcumin could be considered as an integral part of the therapeutic approach for patients with diabetes mellitus.
1. Introduction
The International Diabetes Federation has reported a significant increase in the prevalence of diabetes mellitus (DM), which includes both type 1 (T1DM) and type 2 (T2DM), from 151 million to 463 million cases in adults aged 20 to 79 years since 2000. T2DM is the most common form of diabetes, characterized by high blood glucose levels due to problems with the body's insulin management. This chronic hyperglycemia can lead to an increase in advanced glycation end products (AGEs), resulting in proinflammatory effects and oxidative stress.
2. Role of inflammation
The exact causes of inflammation in T2DM are not yet fully understood, but it appears to contribute to the development of the disease and insulin resistance, which is worsened by hyperglycemia. Epidemiological studies have found a correlation between inflammatory biomarkers and the onset of T2DM and its complications.
Adipose tissue appears to play a significant role in the production of inflammatory biomarkers, due to interactions between adipocytes, macrophages, and other immune cells that contribute to increased adipose tissue (5, 6).
On the other hand, oxidative stress is a key element in the development of T2DM. People with T2DM show increased production of oxidative species and reduced antioxidant capacity. Hyperglycemia contributes to oxidative stress through various mechanisms, including activation of the polyol pathway and induction of glucose autoxidation, leading to increased reactive oxygen species (ROS).
3.Damage from reactive oxygen species
These ROS can cause damage such as reduced glucose transport channels, decreased insulin secretion, protein and DNA damage, generation of free fatty acids, and increased vascular permeability. In addition, oxidative stress contributes to the formation of AGEs, which damage the lining of blood vessels and are linked to microvascular and macrovascular complications of T2DM.
Given the detrimental nature of oxidative stress in the development of T2DM and its vascular complications, the use of antioxidant therapies has been considered as a possible approach.
4. Curcumin
Curcuma longa, a plant widely used as a spice, is recognized for its health benefits. Turmeric contains curcumin, which has been shown to have antioxidant and anti-inflammatory properties. In addition to these properties, curcumin has the potential to prevent and treat various medical conditions, such as infections, diabetes, and cancer .
Studies have indicated that curcuminoids, present in turmeric, can improve insulin resistance, reduce glucose and insulin levels, and influence the levels of various inflammatory biomarkers in patients with T2DM .
These results suggest that curcuminoids may impact glucose homeostasis, diabetes complications, and vascular risk associated with T2DM. Furthermore, curcuminoid supplementation appears to improve lipid profile and total antioxidant in T2DM patients, thereby reducing cardiometabolic risks.
Considering the above, this systematic review focused on the effects of Curcuma longa and its derivatives on diabetes mellitus.
5. Evidence
Publications have shown that the use of Curcuma longa or curcumin (in different formulations) has resulted in a significant decrease in lipid peroxidation, fasting blood glucose levels, glycated hemoglobin (HbA1C), triglycerides, total cholesterol, LDL cholesterol (LDL-c), C-reactive protein, both systolic and diastolic blood pressure. In addition, a significant increase in HDL cholesterol (HDL-c) levels and serum antioxidant capacity has been observed. Some studies have also suggested that curcumin intake may help improve levels of depression and anxiety.
Type II Diabetes Mellitus in Brief
Type 2 diabetes (T2DM) accounts for 80% of diabetes mellitus cases and is a chronic disease characterized by high blood sugar levels. This condition has a multifactorial nature, triggered by several genetic and environmental factors, with a critical mechanism of progressive loss of insulin secretion by β cells. Initially, the patient can compensate for insulin resistance by maintaining normal glycemia, but over time, the disease progresses to hyperglycemia.
Chronic hyperglycemia contributes to increased oxidative stress through increased advanced glycation end products (AGEs) and reactive oxygen species (ROS). This increases the risk of microvascular complications (such as retinopathy, nephropathy, and neuropathy) and macrovascular complications (such as heart failure, stroke, coronary artery disease, and peripheral vascular disease). These complications have a significant impact on quality of life and can reduce the life expectancy of diabetic patients by up to ten years.
Arterial hypertension, dyslipidemia, advanced age, sedentary lifestyle and abdominal obesity are key risk factors for the development of T2DM. Adipose tissue contributes to this process by secreting biomarkers such as resistin, TNF-α and IL-6, which can trigger a chronic inflammatory state and insulin resistance. Low levels of adiponectin and leptin resistance are often observed in obese patients.
The natural progression of diabetes is characterized by hyperglycemia, which contributes to oxidative stress and inflammation, increasing proinflammatory markers and lipid peroxidation. These processes lead to increased factors such as VEGF, ICAM-1, VCAM-1, endothelial dysfunction and apoptosis, which increase the risk of micro and macrovascular complications. Figure 2 summarizes the pathophysiology of diabetes mellitus.
Pathophysiology of diabetes mellitus. Hyperglycemic state leads to increased ROS and proinflammatory biomarkers related to diabetes-related complications. ROS, reactive oxygen species; AGE, advanced glycation end products; MAPK, mitogen-activated protein kinase; NADPHOX, nicotinamide adenine dinucleotide phosphate oxidase; NFKβ, nuclear factor-kappa β; TGF-β, transforming growth factor β; TNF-α, tumor necrosis factor α; IL-6, interleukin-6; VEGF, vascular endothelial growth factor; ICAM-1, intercellular adhesion molecule 1; VCAM-1, vascular cell adhesion protein.
6. Curcuma longa
Curcuma longa is a perennial plant with rhizomatous roots belonging to the genus Curcuma of the family Zingiberaceae, native to subtropical to tropical regions. Turmeric cultivation is widespread in large areas of tropical and subtropical regions of Asia, Australia and South America. Since ancient times, both in India and China, turmeric has been considered a remedy for a variety of ailments, including skin diseases, infections, stress and depression .
Rhizomes are the main part of the plant, and its main active components are curcuminoids , including curcumin, demethoxycurcumin, and bisdemethoxycurcumin. Curcuminoids are non-toxic polyphenols known for their diverse biological activities. They can influence the production of key immunosuppressants that inhibit the production of proinflammatory cytokines such as IL-2 and IL-12. In addition, curcuminoids suppress the expression of enzymes and cytokines such as iNOS (inducible nitric oxide synthase), COX-2 (cyclooxygenase-2), lipoxygenase-5, TNF-α, IL-1, IL-6, and IL-8.
Curcuminoids have been shown to regulate apoptosis, suppress neurotoxic factors in macrophages and alveolar monocytes stimulated by lipopolysaccharides. In addition, they act on the inhibition of phosphorylation and degradation of IκBα (nuclear factor kappa light polypeptide gene enhancer in B cells, inhibitor alpha) and activate peroxisome proliferator-activated receptor γ, reducing the NF-κB pathway-related inflammation pattern.
What makes curcumin particularly interesting to scientists is its antioxidant and anti-inflammatory activity, combined with a remarkably safe pharmacological profile. The unique chemical structure of curcumin gives it the ability to act on different molecular targets, allowing for a broad spectrum of action in different molecular pathways . Among the most significant biological effects is the inhibition of the production of reactive oxygen species (ROS), which play a key role in conditions related to oxidative stress and inflammation, such as diabetes mellitus. Figure 3 illustrates some of the systemic effects of curcumin.
7. Bioavailability
As previously mentioned, curcumin offers a broad spectrum of potential therapeutic benefits, but its low solubility and rapid metabolism limit absorption from the gastrointestinal tract, resulting in limited bioavailability. This is due to its insolubility in water and tendency to degrade rapidly in alkaline solutions or crystallize in acidic environments. The rate of degradation varies greatly with pH, with rapid degradation at pH > 7, taking approximately 30 minutes, while in acidic conditions degradation is considerably slower, with less than 20% of total curcumin decomposed in an hour. When taken orally, most curcumin is excreted in the feces, with only a small fraction absorbed from the intestine, although it undergoes rapid metabolism in the liver and plasma. It is extensively conjugated by glucuronidation and sulfation and converted to water-soluble metabolites (sulfates and glucuronides) which are eliminated in the urine, resulting in low blood concentrations.
The limited bioavailability of curcumin results in reduced serum concentrations, thus decreasing its effectiveness in producing positive health effects. For this reason, in recent years, various administration methods have been developed in order to improve the bioavailability of oral curcumin .
Pharmaceutical technologies and combinations with other compounds, such as piperine or lecithin, have been examined as they increase the solubility of curcumin, prolong its residence in plasma, improve the pharmacokinetic profile and cellular uptake.
New delivery systems, such as solid lipid particles, micellar systems or hydrophilic nanoparticles, can increase the concentration of curcumin up to 15-20 times. As a result, an improvement in curcumin solubility, bioavailability, permeability through cell membranes, plasma half-life, long-term stability, targeted release and therapeutic effects is observed .
8. Safety Studies
Regarding safety, studies conducted on turmeric have shown that the standardized powder and extract of turmeric and curcumin are safe for human use, even at high doses of 6 grams per day for seven weeks. Intravenous use of curcumin is also considered safe as long as the dose administered is lower than that used orally. In studies conducted on pregnant animals, curcumin was considered safe, but more research is needed to confirm its safety in pregnant women.
Curcumin is considered to be a nontoxic, nonmutagenic, noncarcinogenic, and nonphototoxic agent, and is generally considered safe at lower doses than orally administered doses when administered intravenously in humans.
However, it should be noted that turmeric consumption can cause side effects such as dyspepsia, nausea, flatulence, and diarrhea. It has also been shown that turmeric can interact with some drugs, affecting cytochrome P450 and the pharmacokinetics of conventional drugs such as anticoagulants, antibiotics, antidiabetics, cardiovascular drugs, anticancer drugs, and antidepressants .
- In the study conducted by Asadi et al., nano-curcumin supplementation in T2DM patients improved and reduced the severity of DSPN.
- Treatment of T2DM patients with nano-curcumin capsules showed a beneficial effect on depression and anxiety.
- The results of Shafabakhsh et al. revealed that nano-curcumin intervention in T2DM significantly reduced fasting plasma glucose and insulin levels and decreased plasma lipids. In addition, nano-curcumin intake upregulated PPAR-γ and LDLR gene expression in PBMCs and increased total nitrite and total antioxidant capacity (TAC) levels without affecting GSH levels and TGF-β gene expression. The authors concluded that this supplementation showed anti-inflammatory and antioxidant effects.
- The clinical study developed by Mokhtari et al. demonstrated that oral intervention with nano-curcumin in patients with diabetic foot ulcer (DFU) resulted in significant improvement in FPG, insulin levels, homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity control index (QUICKI), LDL-c, TAC and total glutathione (GSH), but did not affect ulcer size, HbA1c, lipid profile, inflammatory markers and oxidative stress.
Conclusions
Studies that met the eligibility criteria for this review showed that curcumin significantly improved insulin resistance, serum glucose levels, HbA1c, lipid profile, and inflammatory biomarkers in patients with T2DM. However, at low doses, for short periods of use, or with a poorly bioavailable molecular form, it may not be as effective on the symptoms of the disease. Since T2DM remains incurable, understanding the role of BIOCURCUMIN in this pathology could represent a new therapeutic target.
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- Ecotoxicol Environ Saf. 2021 Apr 13;216:112211.doi: 10.1016/j.ecoenv.2021.112211.
- Int J Hyg Environ Health. 2021 Apr 13;234:113747.doi: 10.1016/j.ijheh.2021.113747.
- Review Zhongguo Zhong Yao Za Zhi. 2018 May;43(10):2006-2013.
- Volume 2017 | Article ID
6971916 | https://doi.org/10.1155/2017/6971916 - Nutrients. 2015 Jan; 7(1): 552–571.doi: 10.3390/nu7010552
