Comparative Efficacy of Tocotrienol and Tocopherol for their Anti Diabetic Effects

Methodology: This systematic review was carried out following the PRISMA protocol and guidelines. Initially 86(n) articles were included which were than sort out to finally include 05(n). This was done following the pre defined inclusion and exclusion criteria of systematic review. Results: The results strongly supported the inclusion of tocotrienol as part of therapeutic management of diabetes mellitus. The dose can range from 200mg to 430 mg. However, no data was available to identify comparative efficacy of tocopherol. Conclusion: antioxidant, anti-inflammatory anti

tails whereas tocotrienols have unsaturated isoprenoid side chain with three double bonds [2].
With the advent of age, many pathologies used to come on rise. The highlighted ones are the presence of hypertension, type II diabetes, cardiovascular disorders, neurological deficit etc. These all have strong relation with oxidative stress and inflammation.
Here comes the significance for using anti oxidative and antiinflammatory to slow down the disease progression in view to improve quality of life. The isoforms of vitamin E i.e tocotrienol is notorious for both the above-mentioned properties. The reported literature supports that tocotrienols inhibit pathways that are involved in nuclear factor κB (NF-κB), signal transducers, activators 3 (STAT3) and cyclo-oxygenase 2 (COX-2). These all are the ones which activate pathological inflammatory responses. Besides this they are considered as the bioactive form of Vitamin E compared to tocopherols. Hence comes the reason for its application in the therapeutics [3].
Metabolic syndrome (MetS) also known as Syndrome X and Insulin Resistance Syndrome. Metabolic syndrome (MetS) refers to the presence of three or more amongst the five comorbidities: obesity, systemic hypertension, prediabetes/diabetes, insulin resistance, dyslipidemia with reduced HDL levels & hypertriglyceridemia leading to increased risk of cardiovascular disease. MetS involves chronic low-grade inflammation, with elevated serum interleukin 6 (IL-6), IL-1b & CRP levels [4].
It is well known that diabetes mellitus is caused by a deficiency in insulin secretion or by a low response of organs to the action of insulin. Oxidative stress also leads to development & progression of diabetes mellitus, since an exacerbated surge in production of free radicals occurs simultaneously with repressed mechanisms of antioxidant defenses resulting in cellular damage & increased lipid peroxidation and ultimately the development of insulin resistance.
(Savelieff et al. 2020) In another study the beneficial effects of T3s were observed for attenuation of inflammation and insulin resistance especially in overweight or obese women [4].
Around the Globe, management of diabetes mellitus is always a challenging task for the clinician. This is especially true to reduce the emergence of early complications. Therefore, the researchers are devoted to find the solution of this problem. In light of the delicacy of matter, a randomized control trial (RCT) was carried out in 2020, to assess a comparative efficacy of vitamins A, B, C, D&E supplementation on the antioxidant status and glycemic index of type 2 diabetes mellitus patients, The outcomes were measured and compared by various lab tests in pre and post supplementation period. The tests were malondialdehyde (MDA), changes in total antioxidant capacity (TAC), augmentation of glutathione peroxidase (GPx), enhance in superoxide dismutase enzyme (SOD), and thiobarbituric acid reactive substances (TBARS) and glucose levels. It was concluded that supplementation of vitamin E revealed highest antioxidant efficacy [5].

Rationale
The process of aging is a non-modifiable risk factor predisposing to many pathologies. The highlighted one includes hypertension, type II diabetes, hypercholesterolemia, cardiovascular morbidities, and many other degenerative changes. The allopathic medicines impart great significance to address these issues. But besides beneficial effects, many side effects used to be there. Therefore, even with advancement in medical science, there is emergence for a necessity of herbal remedies or plant-based natural compounds.

So alternative form of treatment search is being carried out
Globally. The aim behind the current systematic review is to add up the knowledge for the efficacy of tocotreinol and tocopherol for managing a patient of diabetes with or without insulin resistance.
This will be a step forward to reduce the sufferings and miseries of diabetic patients.

Methodology
This systematic review was carried out by following PRISMA protocol and PRISMA guidelines -2019 [6]. Figure 1

Results
The salient results extracted from the appraisal of 05 selected articles are shown in Table IA. By following PRISMA guidelines and based upon the inclusion and exclusion criteria of study, 05(N) articles were short listed. The standardization of data was done by following critical appraisal skill program (CASP) checklist. Amongst 05 (N) selected articles, 04(n) were the randomized control trials and one was original research article. All of these 04(n) were the registered ones having details for registration bodies and numbers, It is incorporated in Table IA.  (ROS). This is the site of target for antioxidants like for currently extracted evidence and available literature. Antioxidants like tocotrienol helps their modification either enzymatically or nonenzymatically. 5 In one more study efficacy of tocopherol was mentioned as compared to tocotrienol. This is in view that it is the superior isoform of vitamin E. However, the further details were deficient in that particular study to justify this [7].
The pre and post lab investigations to compare disease outcome were done by various tests. They include fasting blood sugar, HbA1c, liver function tests, renal function tests, urine albumin creatinine ratio, e GFR, malondialdehye, thromboxane A2 (TXA2), Vascular cell adhesion molecule (VCAM), advanced cell glycation end product (AGE), soluble receptor for AGEs(sRAGE), Nε-Carboxymethyllysine (Nε-CML), Cystatin C, α-tocopherol concentration and insulin concentration by HPLC and ELISA. This is in favour of many studies, which supports that diabetes complications can be evaluated by these mentioned predictors [7].
The source for tocotrienol-rich vitamin E also came under a debate. The one extracted from palm oil (Tocovid) was found to improve diabetes via its superior antioxidant, antihyperglycemic, and anti-inflammatory properties. In 04(n) studies for current systematic review, the extract of palm oil was used. Only one study, the source was a nut oil. This finding is supported by published data showing efficacy of Tocovid for diabetic nephropathy in patients with T2DM. The parameters used to assess this were HbA1c, blood pressure, Advanced Glycation Endproduct (AGE), soluble receptor for AGE (sRAGE), Nε-Carboxymethyllysine (Nε-CML), and Cystatin C. 5 Another study also supported the efficacious use of palm oil extracted Tocovid for diabetic peripheral neuropathy (DPN). This is due to its anti-inflammatory and anti fibrolytic property, which helps reduction of nerve growth factor (NGF). Thus, neuronal functions will be enhanced, ultimately improving nerve conduction velocities [8].
Amongst the predisposition of diabetes, obesity, chronic finding was observed where duration of study was 24 weeks and 430mg olive oil extract as a source of totoctrienol was used and significant effects were observed to improve quality of life for diabetic patients [11,12].

Conclusion
Tocotreinol because of its antioxidant, anti-inflammatory and anti fibrolytic properties helps marinating the glycemic levels in diabetic patients. Besides this the emergence of diabetic complications was delayed. A clinical improvement in patients with diabetic nephropathy and neuropathy was seen as well. It was also observed that grape seed oil supplement of tocotrienol was proven beneficial as compared to sunflower oil supplement especially by lowering inflammatory markers. f) Therefore, this became a big limitation of study and only included articles were focused for assessing efficacy of tocotrienol on diabetes.

1.
Tocotrienol is found effective in managing the diabetic patients.
So prospective randomized control trials (RCTs) over longer period should be carried out to study its beneficial effects 2. The currently available RCTs, have shown maximum follow up duration uptil 03 months.

3.
The dose adjustment of tocotrienol needs to be calculated carefully in cases for follow up for more than 03 months.

5.
None of the available studies reported the side effects of tocotrienol. For longer duration follow up studies, it should be evaluated cautiously.
6. The efficacy of tocopherol needs to be explored for antidiabetic effects 7. The comparative analysis of tocotrienol and tocopherol needs to be carried out for exploring anti diabetic effects.

8.
Incorporation of tocotrienol as part of diabetic patients' management helps lowering the risk of diabetic nephropathy, diabetic neuropathy and end stage renal disease.

9.
Comparative efficacy for grape seed supplement was proven beneficial as compared to sunflower oil supplement for diabetic patient management.