Cardiovascular Study

Cardiovascular diseases (CVDs) are the number 1 cause of death globally. According to a WHO report, an estimated 17.9 million people died from cardiovascular diseases in 2016 representing 31% of all global deaths in 2016. Out of these, 85% were due to heart attack and stroke. Cardiovascular disease, listed as the underlying cause of death, accounts for nearly 836,546 deaths in the US. That’s about 1 of every 3 deaths! About 2,300 Americans die of cardiovascular disease each day, an average of 1 death every 38 seconds! In fact, cardiovascular diseases claim more lives each year than all forms of cancer and chronic lower respiratory diseases combined. Coronary heart disease is the leading cause (43.8%) of deaths attributable to cardiovascular disease in the USA, followed by Stroke (16.8%), Heart failure (9%), High Blood Pressure (9.4%), diseases of the arteries (3.1%), and other cardiovascular diseases (17.9%).

According to the American Heart Association, a new clinical study using DeltaGold Annatto Tocotrienol (Eannatto) which contains 90% Delta and 10% Gamma Tocotrienol was conducted and ‘Potential cholesterol lowering effects of tocotrienols were observed to involve post-transcriptional suppression of HMGR (3-hydroxy3methyl-glutaryl-CoA reductase-the enzyme/protein responsible for the body’s cholesterol production)’. Also, in a study, ‘Tocotrienol is a cardio – protective agent against ageing – associated cardiovascular disease and its associated morbidities’, superior anti – oxidative and anti – inflammatory activity of Tocotrienols were observed when compared to that of Tocopherols in ameliorating ageing – related cardiovascular diseases and its associated morbidities. In particular, the potential of Tocotrienols in improving inflammaging, dyslipidemia and mitochondrial dysfunction in ageing – related cardiovascular diseases were observed.

Most research in the past 50 – 60 years has been focused on Tocopherols and 50% of all the research in last 30 years has been done on Tocotrienols in last 5 years. Half of the Tocotrienol research ever published has been published in last 10 years as shown in Fig. 1. Each day it is becoming increasingly understood that Tocotienols (especially Eannatto – DeltaGold) are the right form of Vitamin E. Well in excess of 100 studies and clinical trials have shown the surprising benefits of Tocotrienols – without any known side effects.


Fig. 1:
In the graph, as you can see, R & D on Tocotrienol has increased exponentially over the years in all fields while research on Tocopherols has decreased. Whether it is cancer, Cardiovascular diseases (CVD), Diabetes, Anti – Oxidant activities or others, in all fields research on Tocotrienol has not only gained pace but quant as well.

Study 1 - Potential cholesterol lowering effects of tocotrienols were observed to involve post – transcriptional suppression of HMGR (3-hydroxy3methyl-glutaryl-CoA reductase-the enzyme/protein responsible for the body’s cholesterol production).

Scientists from the University of Missouri – Kansas City reported that Tocotrienol doses ranging from 125 – 750 mg/day combined with the healthy diet decreased lipid levels significantly after only 4 weeks, with 250 mg/day found to be the optimal dose.

“The results confirm that consumption of Delta – Tocotrineol plus AHA Step – 1 diet causes significant reduction in serum lipid parameters and several cytokines at a low optimal dose,” concluded the researchers, led by Dr. Ashraf Qureshi, a pioneer in Vitamin E Tocotrienol research.

The potential cholesterol lowering effects of Tocotrienols are reported to involve post – transcriptional suppression of HMGR (3 – hydroxyl – 3 – methyl – glutaryl – CoA reductase – the enzyme/protein responsible for the body’s cholesterol production) via controlled degradation of the reductase protein. This protein degradation is reportedly only seen with Delta – Tocotrienol and Gamma – Tocotrienol. In the current study, researchers tested the effects of Annatto Tocotrienoldoses ranging from 125 – 750 mg per day on 31 people with elevated cholesterol levels. Results showed that after only 4 weeks, the optimum daily dose of 250 mg decreased total cholesterol by 15%, LDL cholesterol by 18%, and triglycerides by 14%.

Furthermore, cytokines associated with cardiovascular disease and their gene expression, including TNF – alpha, IL – 2, IL – 4, IL – 6, and IL – 8, were down – regulated 39 – 64%. Selected microRNAs that are typically down – regulated in hypercholesterolemic individuals were up – regulated by Tocotrienolstreatment, suggesting a beneficial effect on these biomarkers.

A lack of lipid – lowering effects with the smaller 125 mg daily dose may have been remedied by extending the treatment period to 8 weeks, said the researchers. Higher doses of 500 mg and 750 mg, however did not decrease lipids compared to baseline. None of the participants reported any adverse events throughout the course of the study, indicating the supplement’s safety across the range of dosages utilized.

Commenting on the research, Dr. Barrie Tan, president of American River Nutrition Inc. said: “Dr. Asaf Qureshi has pioneered Tocotrienol research for nearly 35 years. His work continues to yield critical studies, particularly in connection to Delta – Tocotrienols and Gamma – Tocotrienols.”

Study 2 - Tocotrienol is a cardio – protective agent against ageing – associated cardiovascular disease and its associated morbidities.

Ageing is a non – modifiablerisk factor that is linked to increased likelihood of cardiovascular morbidities. Whilst many pharmacological interventions currently exist to treat many of these disorders such as statins for hypercholesterolemia or beta – blockers for hypertension, the elderly appear to present a greater likelihood of suffering non – related side effects such as increased risk of developing new onset type – 2 diabetes (NODM). In some cases, lower efficacy in the elderly have also been observed. Alternative forms of treatment have been considered to address these issues, and there has been a growing interest in looking at herbal remedies or plant – based natural compounds. Oxidative stress and inflammation are implicate in the manifestation of ageing – related cardiovascular disease. Thus, it is natural that a compound that possesses both anti – oxidative and anti – inflammatory bioactivities would be considered. In this study, the potential of Tocotrienols with proven superior anti – oxidative and anti – inflammatory activity compared to Tocopherols in ameliorating ageing – related cardiovascular diseases and its associated morbidities. In particular, the potential of Tocotrienols in improving inflammation, dyslipidemia and mitochondrial dysfunction in ageing – related cardiovascular diseases are discussed.

Also, in 2001, researchers tested Tocotrienols for their ability in reducing plaque buildup in arteries. This four-year study from Elmhurst Medical Center in Queens, New York, involved 50 participants who had the plaque in their carotid arteries, the major arteries that carry blood to the brain. Among the participants who took 240 mg of Tocotrienols a day along with 60 mg of Alpha-Tocopherols, an amazing 88% experienced either no increase in plaque or even reduction in plaque. But, the participants taking a placebo, 80% of them experienced a worsening in their condition.

In a study conducted in 2015, several people with high cholesterol took supplements ranging from 125-750 mg/day of Tocotrienols for 4 weeks. It was observed that on average, total cholesterol levels were lowered by 15 percent LDL cholesterol dropped by 18% and triglycerides decreased by 14%. The levels of inflammatory chemicals associated with cardiovascular diseases, called cytokines, were also reduced – and by a whopping 64%! Other kinds of research have also shown that when Tocotrienols were combined with plant-derived anti-oxidant polyphenols, Delta-Tocotrienol (Eannatto – DeltaGold) which is one of the four forms of Tocotrienols, reduced inflammation and lowered lipids associated with atherosclerosis as shown in Fig. 2 and Fig. 3.


Fig. 2: Dr. Qureshi, the father of Tocotrienol functions observed in his study that when he took 125mg, 250 mg, 500mg and 750 mg of Tocotrienols, at 250mg, total Cholesterol was lowered by 15%, LDL by 18% and Triglyceride by 14%.

Clinical Study
Fig. 3: In the study conducted by Dr. Qureshi, he saw that at 250 mg of Tocotrienols, the endogenous anti-oxidant, TAS (represented with grey colour) increased, while the C-reactive protein (CRP) dropped by 40%, oxidized fat (MDA) dropped by 34% and Total Anti-oxidant increased by 22%.

Scientists from the University of Missouri – Kansas City reported that Tocotrienol doses ranging from 125 – 750 mg/day combined with the healthy diet decreased lipid levels significantly after only 4 weeks.

Summary

Why Tocotrienol?

  • Antioxidants, especially Tocotrienol was observed to exhibit anti-cancer activity against breast cancer cells by lowering inflammation and oxidative stress as shown in Fig. 4.
    Clinical Study
    Fig. 4: In the study conducted by Dr. Qureshi, he saw that at 250 mg of Tocotrienols, the endogenous anti-oxidant, TAS (represented with grey colour) increased, while the C-reactive protein (CRP) dropped by 40%, oxidized fat (MDA) dropped by 34% and Total Anti-oxidant increased by 22%.
  • Cholesterol reduction is a significant feature of Tocotrienols by suppression of HMGR (3-hydroxy3methyl-glutaryl-CoA reductase) the enzyme/protein responsible for the body’s cholesterol production.
  • Cytokines associated with cardiovascular diseases were down-regulated by Tocotrienols according to the study done at the University of Missouri – Kansas City.
  • MicroRNAs which are usually down-regulated in hyper-cholesterolemic individuals are up-regulated by Tocotrienol treatment as per the study.
  • Cellular adhesion molecule expression has been observed to be reduced by Tocotrienols.
  • Monocytic cell adherence has also been found to be reduced by Tocotrienol in multiple kinds of research.
  • ‘Velcro effect” or Chemotaxis a process which initiates plaque formation in arterial walls and Atherosclerotic Lesion have also been observed to be reduced by Tocotrienol as shown in Fig. 5 and Fig. 6.


    Fig. 5:
    In a Japanese study, it was observed that when Alpha-Tocopherol was used, no change was observed towards the treatment of Atherosclerosis but when it was treated with 0.2% Delta-Tocotrienol, there was a 24% decrease in Atherosclerotic Lesion.

Fig. 6: In a Malaysian study, the inflammation marker was observed to drop at both established period of plaque and early period of plaque formation in arteries. Adhesion molecules like Vasco – cellular adhesion molecules (VCAM), Intra – cellular adhesion molecules (ICAM) etc. cling on to the arterial walls and bring on microphages and cholesterol and form plaque but Tocotrienols were observed to inhibit adhesion molecules thus preventing plaque formation. Proteolytic enzymes which also encourage plaque formation were also observed to be reduced.
  • Lipid peroxidesin blood vessels and blood pressure have been observed to be lowered by Tocotrienols which improves total anti-oxidant status thus preventing hypertension.
  • Carotid Arteriosclerosis has been observed to be reduced by Tocotrienol in several studies.
  • Anti-inflammation are characteristic properties of Tocotrienols.

Dosage

  • Scientists from the Universityof Missouri – Kansas City report that Tocotrienol doses ranging from 125 – 750 mg/day combined with the healthy diet decreased lipids.
  • Substances that complement Tocotrienol forhigh lipids include CoQ10, Omega – 3 fatty acids, Glucosomine, Chondroitin.
  • Substances that complement Tocotrienol for Cardiovascular diseases and MetS include CoQ10, Omega – 3 fatty acids, Magnesium, Resveratrol, Red Yeast Rice, MK4, MK7.

Why Tocotrienol and not Tocopherol?

  • Ineffective Tocopherol: Large clinical studies on alpha-tocopherol have shown it to be ineffective and possibly harmful. Also, Tocopherols do not have the cholesterol-lowering ability which Tocotrienols do.

Fig. 7: When a 275 mg/day of dose of Tocotrienol was given with 33% Alpha – Tocopherol for 48 months, it was observed that only 14% LDL was decreased while there was no change in Triglycerides. When a 200 mg/day of dose of Tocotrienol was given with 33% Alpha – Tocopherol for 1.5 months, it was observed that there was no change in either LDL or Triglycerides. When a 100 mg/day of dose of Tocotrienol was given with less than 10% of Alpha – Tocopherol for 1 month, it was observed that LDL decreased by 20% and Triglycerides decreased by 8%. When a 100 mg/day of dose of Tocotrienol was given with 0% of Alpha – Tocopherol for 1 month, it was observed that LDL decreased by 20% and Triglycerides decreased by 15% and when a 75 mg/day of dose of Tocotrienol was given with 0% of Alpha – Tocopherol for 2 months, it was observed that LDL decreased by 15% and Triglycerides decreased by 20%.
  • The inability of Tocopherol to regulate Cholesterol Synthesis: While Tocopherol has antioxidant value, they lack the ability to regulate cholesterol synthesis.
  • Structure of Tocotrienol:Tocotrienol has a smaller structure and less molecular weight which helps it to move freely through the cell membranes to cover larger areas for added protection.
  • Tocopherol, the enemy of Tocotrienol: Alpha-tocopherol has been observed to attenuate or interfere with the cholesterol-lowering function of Tocotrienols. Preparations effective in cholesterol-lowering action consist of 15% or less of alpha-tocopherol and 60% or more gamma and delta Tocotrienols while ineffective preparations consist of 20% or more alpha-tocopherol and 45% or less of gamma and delta-tocotrienols.
  • Absorption: As compared to Tocopherols, Tocotrienols absorb better in the body and Tocopherols have been observed to prevent absorption of Tocotrienols.

    Fig. 8: The 2nd pie chart represents Palm Tocotrienol rich fraction with 32% Alpha – Tocopherol which was given to people and when the Alpha – Tocopherol was removed then it was represented by the 1st pie chart with 0.3% Alpha – Tocopherol which was then given to people. In the graph, the hollow bar represents the Tocotrienol with Tocopherol which reduced the concentrations of Alpha, Gamma and Delta Tocotrienol in the body but when Tocopherol was removed from the dosage (Solid grey bars in graph), the concentrations of Alpha, Gamma and Delta – Tocotrienol significantly increased.

References

Note:

  • To read studies in detail, follow the references and links given.
  • The dosages given must not be taken as the advice of a medical practitioner. Consult your physician for the optimum dosage to be consumed.

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