In the literature and teaching to this day it is still argued that "vitamin E"  would be covered best by only one of the eight isomers, namely alpha-tocopherol. It would be “most bioavailable.”

This is a false lead that has already led to many misunderstandings and failed studies. In fact, there is a transport protein (aTTP) in the body that strongly prefers alpha-tocopherol. But this is only because it selects the storage form of vitamin E, namely the slowest and most inert version - alpha-tocopherol. The other isomers of vitamin E have been neglected in research for a long time, although they have a significantly higher antioxidant effect and some important additional effects.

The higher isomers (tocotrienols) are therefore not “hardly effective aberrations of nature”. They specifically serve their own purposes.

The alpha-tocopherol (aTP for short) even has some harmful effects when it is added artificially. For example, it even works in larger quantities pro-oxidative so it does exactly the Opposite of what it is supposed to do. It also oxidizes LDL cholesterol and increases cholesterol production. And it displaces the other important isomers from transport in the body and in the cells.

Thanks to tocotrienol-vitamin E, vitamin E is now available, which does not have these harmful effects and which can also be easily increased in quantity. You can see this very well in the studies dealing with cholesterol.

Brief summary: the proportion of alpha-tocopherol of total vitamin E should not exceed 27%. Therefore, nutritional supplements with alpha-tocopherol and very vitamin E-heavy foods should perhaps be avoided.

Cholesterol-stuthes with tocotrienol and the influence of alpha-tocopherol

Tocotrienols can reduce blood cholesterol levels by 10% - 15%, which has been proven for many years by studies with humans and animals. In individual cases, significantly more could even be achieved.

However, there are a number of “failed” studies – without significant changes in blood lipids. Upon closer inspection, it turns out that all of these studies used a proportion of 29% or more alpha-tocopherol than total tocochromanols (examples: [9][10][11]). When it comes to blood lipids, alpha-tocopherol is not only ineffective, it even disrupts the effect of the tocotrienols. Alpha-tocopherol can increase cholesterol production [6]. Alpha-tocopherol has a pro-oxidative effect on LDL [17].

[6] used animals to investigate the amounts of alpha-tocopherol (in relation to tocotrienol) and how severely the cholesterol reduction is affected. At 33% the effect is largely lost, at 24% and below the effect persists. In [4] the ATP was specifically removed because the mechanism was known.

Tocotrienols are now extracted from some natural plant oils.

Extractions from rice have approx. 50% atP, from palm trees 20 to 29% atP, from annatto 0%.

This means that the tocotrienols from rice do not work in blood lipids, but tocotrienols from annatto certainly work. Tocotrienols from palm trees only work in good quality (<25% aTP), which can be significantly exceeded in material from PFAD (cheaper productions) or by tocopherols from food or food supplements.

Even in successful studies there were “non-responders”, i.e. individual people who were hardly less responsive to the intervention - this can now be explained by additional alpha-tocopherol - for example from food supplements.

Successful studies

study [1] used tocotrienols with 20% aTP (160 mg tocotrienol and 40 mg aTP) successfully.

Result: Total cholesterol - 15%, HDL cholesterol +9%.

In the second part of this study, 200 mg ra gamma-tocotrienol was used.

Result: Total cholesterol -31%, LDL cholesterol -27%, TG -15%.

study [4] with very good results used tocotrienols from rice, which usually have a high percentage of ATP. For this study, the ATP was used under 9% reduced (now 40% gamma-T3). The study participants were divided into 5 groups and subjected to the AHA (American Heart Association) Step-1 diet for 35 days and were provided with tocotrienolsn in various doses.

Result: Alla through the diet has already achieved an improvement in the parameters by up to 5%. By adding and increasing the tocotrienols from 25 mg/d to 200 mg/d, these values ​​further improved as follows:

Between 100 and 200 mg of tocotrienol there was an optimal effect of almost 20% cholesterol reduction, of which almost 5% was returned to the diet.

study [12] with 19 type 2 diabetics used 3 mg/kg body weight TRF with less than 10% aTP and 40% gT3 for 60 days.

Result: After 60 days, total lipids, TC and LDL-C were reduced by 23, 30 and 42%. LDL-C was reduced from an average of 179 mg/dl to 104 md/dl. However, a reduction in blood sugar was not observed.

The standard medication to lower cholesterol is statins, which, however, have frequent and serious side effects (muscle wasting, skin peeling, allergies, headaches, nausea, indigestion, muscle, joint and back pain, increased blood sugar, insomnia, ringing in the ears, drowsiness, numbness, pancreatitis, hepatitis).

For people who refuse to take statins or want to reduce their intake, 100 to 250 mg of tocotrienols may represent an interesting and easily verified alternative to statins. If the intake of alpha-tocopherol is kept under control, 10 to 20% reductions in total cholesterol can be achieved without side effects. At the same time, other important parameters against atherosclerosis (e.g. coagulation and MDA) as well as other areas (brain, liver, inflammation) are also positively influenced.

Other parameters: MDA, CRP, delta-GT, NO, TAS

Since 2015, [3] has been a clinical study that examined other important parameters in blood and determined the optimal dosage range. C-reactive prota (CRP), malondialdehyde (MDA), δ-glutamyl transferase (δ-GT), serum nitric oxide (NO), total antioxidant status (TAS), cytokines/protas, cDNA and microRNAs were examined. With 31 hypercholesterol (>5.2 mmol/L) subjects on different dosages and concurrently with the AHA Step 1 diet.
Annatto-tocotrienol (90% delta-T3, 10% gamma-T3) 125 – 750 mg/d was used.

Result: CRP -40%, MDA -34%, δ-GT -22%, NO -40%, TAS +22% (P<0.001) Inflammatory plasma cytokine (resistin, IL-1a, IL-12, IFN-g) - 15-17% (P<0.05-0.01)
FGF-b (cardiac angiogenic fibroblast growth factor-b) -11% other
PDGF (platelet-derived growth factor)-14% (P<0.05-0.01)
Since tocotrienols are excellent antioxidants, the antioxidant status improved significantly - which should reduce cholesterol oxidation.

All effects increased dose-dependently up to 250 mg/d and decreased from 500 mg.

HAEC (endothelial cell) adhesion

For atherosclerosis to develop, plaques must attach to the endothelial cells. Adhesion factors determine this attachment and these can be significantly reduced by tocotrienols. It was measured by [5] that the attachment of monocytes to HAEC increased significantly after pretreatment with tocotrienolsn58% to 73% reducedbecame. The effect was most noticeable in delta-tocotrienol (-73%).

Interestingly, human endothelial cells prefer tocotrienols by a factor of 25 to 95 compared to alpha-tocopherol. In particular, for delta-tocotrienol, which also showed the strongest effect against cell adhesion, the HAEC had an 85-fold stronger preference compared to alpha-tocopherol.

References

1. [PMID: 2012010] Lowering of serum cholesterol in hypercholesterolemic humans by tocotrienols (palmvitee). At J Clin Nutr. 1991 Apr;53(4 Suppl):1021S-1026S.

2. [PMID: 21489303] tocotrienols-induced inhibition of platelet thrombus formation and platelet aggregation in stenosed canine coronary arteries
   Lipids Health Dis. 2011; 10: 58. Published online 2011 Apr 14. doi: 10.1186/1476-511X-10-58

3. [DOI: 10.4172/2155-9880.1000367]Journal of Clinical & Experimental Cardiology 2015
   Impact of δ-tocotrienol on Inflammatory Biomarkers and Oxidative Stress in Hypercholesterolemic Subjects

4. [DOI: 10.1016/S0021-9150(01)00619-0 Atherosclerosis 2001
   Dose-dependent suppression of serum cholesterol by tocotrienol-rich fraction (TRF 25 ) of rice bran in hypercholesterolemic humans
   https://www.atherosclerosis-journal.com/article/S0021-9150(01)00619-0/pdf

5. [PMID 15823271] tocotrienols reduce 25-hydroxycholesterol-induced monocyte-endothelial cell interaction by inhibiting the surface expression of adhesion molecules

6. [PMID 22692474] (Full text original at www.researchgate.net)

7. Dose-Dependent Cholesterolemic Activity of tocotrienols and α-Tocopherol Mal J Nutr 8(2): 157-166, 2002

8. [PMID: 8614310] Antioxidant effects of tocotrienols in patients with hyperlipidemia and carotid stenosis. Lipids. 1995 Dec;30(12):1179-83.

    

9. [PMID: 18481320] tocotrienol-rich fraction of palm oil exhibits anti-inflammatory property by suppressing the expression of inflammatory mediators in human monocytic cells.
   Mol Nutr Food Res. 2008 Aug;52(8):921-9. doi: 10.1002/mnfr.200700418.
10. [PMID: 28912593]
    Effect of palm-based tocotrienols and tocopherol mixture supplementation on platelet aggregation in subjects with metabolic syndrome: a randomized controlled trial
11. [PMID: 9989682]
    A vitamin E concentrate rich in tocotrienols had no effect on serum lipids, lipoprotas, or platelet function in men with mildly elevated serum lipid concentrations.
12. [PMID: 27295311] α-Tocopherol Attenuates the Triglyceride- and Cholesterol-Lowering Effects of Rice Bran tocotrienol in Rats Fed a Western Diet.
13. [PMID:16159610] The therapeutic effects of tocotrienols in type 2 diabetic patients with hyperlipidemia.
    Atherosclerosis.2005 Oct;182(2):367-74. Epub 2005 Apr 20.

14. [PMID 21673716] J Cereb Blood Flow Metab. 2011 Nov;31(11):2218-30. tocotrienol vitamin E protects against preclinical canine ischemic stroke by inducing arteriogenesis.

15. [PMID 24373555] tocotrienols for normalization of hepatic echogenic response in nonalcoholic fatty liver: a randomized placebo-controlled clinical trial.Nutr J.2013 Dec 27;12(1):166. doi: 10.1186/1475-2891-12-166.

16. [PMID 25231142] tocotrienols have a nephroprotective action against lipid-induced chronic renal dysfunction in rats.Ren Fail.2015 Feb;37(1):136-43.

17. [PMID 30227659] tocotrienol-Rich Vitamin E from Palm Oil (Tocovid) and Its Effects in Diabetes and Diabetic Nephropathy: A Pilot Phase II Clinical Trial.Nutrients.2018 Sep 17;10(9).

18. [PMID 15380467] Pro-oxidative effect of alpha-tocopherol in the oxidation of LDL isolated from co-antioxidant-depleted non-diabetic hemodialysis patients. Clinical Trial Atherosclerosis.2004 Oct;176(2):411-8.

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