#41

Hi and thank-you for the link.
So, I am a cancer survivor x 3, so which LE Vitamin E name, of the ones that I see via the LE link, could be more appropriate? (My endocrinologists x 3; Oncologist and GP MDs have suggested NO supplements. My Geneticist suggested a probiotic, Fisiten and Tru Niagin which Ibtook for awhile.
Sadly, my cardiologist doesn’t consult with the other MDs. None of my MDs consult with each other about anything.
Anyway, I understand that you’re not diagnosing or treating me or my medical conditions; rather just sharing what i think might be something for me to consider and to mention to my medical healthcare providers.
With appreciation,
Jan

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#42

“All of these and more make it important to learn more about the effects of ezetimibe on the assimilation of tocopherols and tocotrienols.”

Can you cite any human studies to that effect? I don’t seem to find any.
“Overall, only the animal study provided evidence directly related to the question, suggesting ezetimibe may inhibit α-tocopherol assimilation”
The study I looked at was in rats and the effect can be reduced by several hours spacing between ezetimbe intake and α-tocopherol. I can find no studies indicating that ezetimibe has any effect on delta-tocotrienol. In any case, I don’t think it is a big deal.

I am always surprised to find at this late date supplements I have never heard about, i.e. delta tocotrienols.

Early vitamin E researchers were so impressed by the life extension results of vitamin E supplementation on cells, worms, etc., that they immediately started supplementing themselves.
Of course, we now know that is not the case, and supplementing vitamin E ((alpha-tocopherol) in excess is harmful.

Perhaps it was the delta and gamma forms that produced the amazing results.

However, it doesn’t appear that tocotrienols significantly reduce cholesterol levels, but it does increase HDL-C. “The present meta-analysis demonstrated that supplementing with tocotrienols does not decrease the concentrations of LDL-C, TC and TG. However, tocotrienol supplementation was considered a candidate for increasing HDL-C levels.”
(IMO: Pantethine is the best add-on supplement to lower cholesterol.)

Tocotrienols have been shown to reduce CRP levels, which I find is good news and I will be adding a tocopherol free tocotrienol supplement to my stack. Supplements containing only
tocotrienols (delta-tocotrienol & gamma-tocotrienol) and zero alpha-tocopherol can be found on Amazon.

The evidence is rather weak and there are not that many studies, but I think it might be worth a try to lower CRP levels.
Increasing HDL and lowering LDL and triglycerides would be a bonus.

I am not going to list all of the references, but here is a synopsis:

A clinical trial in patients with nonalcoholic fatty liver disease found 300 mg/day δ-tocotrienol for 12 weeks significantly decreased serum high-sensitivity CRP compared to placebo ([3]).

Two separate clinical trials in patients with nonalcoholic fatty liver disease found 300 mg/day δ-tocotrienol for 24 weeks significantly reduced serum hs-CRP levels compared to placebo ([5], [7]).

Three human studies in hypercholesterolemic subjects found doses of 250-750 mg/day δ-tocotrienol for 4-6 weeks significantly reduced serum CRP levels from baseline ([6], [2], [8]).

A clinical trial in type 2 diabetes patients found 250 mg/day δ-tocotrienol for 24 weeks significantly decreased serum hs-CRP compared to placebo ([7])

"The most effective dose of tocotrienols (250 mg/day) may be used to lower serum NO (40%), CRP (40%), MDA (34%), γ-GT (22 %), and inflammatory cytokines IL-1α, IL-12, IFN-γ by 15% to 17%, and increase TAS levels by 22%.

“Inhibitory effect of ezetimibe can be prevented by an administration interval of 4 h between α-tocopherol and ezetimibe”

Effects of delta-tocotrienol supplementation on Glycemic
Control, oxidative stress, inflammatory biomarkers

Full-text link: Sci-Hub | The effects of tocotrienol supplementation on lipid profile: A meta-analysis of randomized controlled trials. Complementary Therapies in Medicine, 102450 | 10.1016/j.ctim.2020.102450

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#43

Yes. The role of ezetimibe as related to the role of the tocopherols and tocotrienols in the general topic we are discussing is a complicated story. The story is unfinished in my opinion. Unfortunately I am only in the early to mid-stage of unpacking what is and is not known about ezetimibe’s interference with the assimilation of oil soluble vitamins. I’ll post when I learn more but I believe I can already see that we may reach some dead ends due to the lack of specific empirical evidence. A few thoughts when considering these issues.

  • The economic incentives for pharma finding that ezetimibe does not materially interfere with the assimilation of important nutrients are great. A review of the history of statins and CoQ-10 is relevant here.

  • The phase trials that the no interference claim is based on has reasonably high precision and low realism. I have not seen the actual datasets but the operational definitions for interference would likely not satisfy most of us.

  • Given that EOD (48 hour span) doses of ezetimibe result in only slightly reduced efficacy in terms of reducing the assimilation of LDL-C, etc., it is difficult to see the logic by which a four-hour delay between ingesting ezetimibe and swallowing a tocotrienol or tocopherol tablet, especially with a meal containing other fats, eliminates the assimilation problem. Perhaps the claim is true for reasons of which I am unaware but I have not seen randomized controlled evidence to that effect.

  • In medicine, meta-analyses can and frequently does mischaracterize the generalization of valid empirical relationships. While this research tool is one of many capable of increasing our understanding, it tends to be more challenging to execute well in medicine due to practical challenges carrying high inferential significance in setting the lowest common denominator for including datasets. If I am interested in the subject line of a medical study, my position is to first look to the selection parameters, especially the excluded studies, before considering the findings. The rejection rate can be high, as is should be.

  • Beyond the practical limits of meta-analysis, this approach requires a kind of artificial precision that ignores and in doing so minimizes considerations of realism; i.e., they become more precise about less typical human setting conditions. This is the case with much of the research on the tocopherol/tocotrienol family.

  • Not directly on point but the history of the tocopherols, including how alpha tocopherol came to be the standardization criterion based on a single first determined property is illustrative of the kind of conceptual problems which can then drive decades of weakened empirical research. The harmful effects of alpha tocopherol and its harmful effects in certain contexts and doses is one example of such research. Other tocopherols, especially gamma, should be the health target even though the law requires standardization on the alpha form. I take a mixed blend including tocotrienols, but also take a refined delta tocotrienol. Large doses are not needed for any in this family.

Again, perhaps someone has already looked at the actual operational definitions and datasets or at least the basic representations of the studies of interest and can save us all some time. In the meantime, I have decided to increase my dose of tocopherols and tocotrienols by roughly 50% hoping, with little good evidence, that this increase is enough to offset potential losses from ezetimibe while having no specific downside if there are no such losses.

4 Likes
#44

Thanks. I halved my dose of ezeitimibe (broke pill in two). Maybe I should do EOD? My original concern was absorption of fish oil / omega 3s.

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#45

Still piecing this together but it looks like all vitamin E homologs (i.e., tocopherols and tocotrienols) are mediated by Niemann-Pick C1-like 1 (NPC1L1) transporter protein. NPC1L1 is a polytopic transmembrane protein. It functions as a sterol transporter that mediates intestinal cholesterol absorption and counterbalances hepatobiliary cholesterol excretion.

There are a few points in this process that I do not yet understand but the translation is, Yes, contrary to some claims, it appears that ezetimibe inhibits the assimilation of all members of the vitamin E family along with members of the cholesterol family.

If this holds up, and it may not, the question then on the table is how can ezetimibe do its job for 24-48 hours or more yet suspend doing that job four hours after ingestion. A related question is whether Omega-3 is caught up in this process.

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#46

And you do not have randomized control trials supporting your assumptions.

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#47

The following information, along with the phase 3 RCT on vitamin E that was abandoned due to the number of lung cancer cases vs placebo has made me avoid vitamin E supplementation like the plague. Beta Carotene is associated with an 8% HIGHER all cause mortality rate. Vitamin E is also associated with a 15,400% increase in skin cancer, something I am already genetically predisposed to. I am skipping this one.

In contrast, vitamin E supplement use was associated with increased lung cancer risk (HR: 1.33; 95% CI 1.01-1.73) , more so for lung adenocarcinoma risk (HR: 1.79; 95% CI 1.23-2.60).

Vitamin E intake and the lung cancer risk among female nonsmokers: a report from the Shanghai Women’s Health Study - PMC).

Among the 876 new cases of lung cancer diagnosed during the trial, no reduction in incidence was observed among the men who received alpha-tocopherol (change in incidence as compared with those who did not, -2 percent; 95 percent confidence interval, -14 to 12 percent). Unexpectedly, we observed a higher incidence of lung cancer among the men who received beta carotene than among those who did not (change in incidence, 18 percent; 95 percent confidence interval, 3 to 36 percent). We found no evidence of an interaction between alpha-tocopherol and beta carotene with respect to the incidence of lung cancer. Fewer cases of prostate cancer were diagnosed among those who received alpha-tocopherol than among those who did not. Beta carotene had little or no effect on the incidence of cancer other than lung cancer. Alpha-tocopherol had no apparent effect on total mortality, although more deaths from hemorrhagic stroke were observed among the men who received this supplement than among those who did not. Total mortality was 8 percent higher (95 percent confidence interval, 1 to 16 percent) among the participants who received beta carotene than among those who did not, primarily because there were more deaths from lung cancer and ischemic heart disease.

http://www.nejm.org/doi/full/10.1056/nejm199404143301501

Vitamin E increased the number of skin tumors in mice from 1 tumor/25 animals in the control group to 154 tumors/26 animals in DMBA treated mice, giving an increase of 15,400%.

http://www.sciencedirect.com/science/article/pii/S2213231714001414

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#48

Yikes, not good for me, cancer survivor x 3.
Thanks for enlightening me. Sincerely, Jan

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#49

I do not currently take a statin, but will have that conversation with my doctor this week. So, this topic is of interest. However, I have a general question: Has anyone tried using sterols and stanols to reduce LDL-C and Apo B? I am specifically referring to the Benecol products. I believe there is another product called Cholestin, too.

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#50

Yes, stanols/sterols work, but there are risks involved.

Somewhere in 1:26:

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#51

I got good but modest results with stanols and sterols a few years back but did not like the very issues discussed in this podcast posted by @tj_long. Good listen. Good discussion on berberine as well somewhere around 1:30 in. One additional point on berberine is that it has antibacterial effects which could affect the gut biome positively or negatively, whether good or bad possibly depending on one’s unique biochemistry.

1 Like
#52

Following up on the question of ezetimibe and the assimilation of some fat soluble nutrients such as the tocopherols, I finally had a few minutes to review the study by Japanese researchers finding that a four hour window between ezetimibe and the ingestion of vitamin E addresses the assimilation problem. Some will see this differently but I find the study to be of low relevance for three reasons. The generalization reflected in the study title is based on research on rats where generalizations to humans are weak and highly variable. The research design does not mirror actual human use well. The entire study is based on alpha-tocopherol, which has been known for a few decades to present a complex health equation with known risks and benefits. Too many studies attempt to generalize the benefits of vitamin E based on narrowly defined research with synthetic alpha tocopherol. In this case, I could not discern from the abstract whether d- or dl- alpha tocopherol was employed in the study. Natural alpha-tocopherol is a single stereoisomer, while the synthetic form is a combination of eight stereoisomers. Its actions are different and virtually all studies use the synthetic form.

1 Like
#53

Hi, I regulary use Benacol as one of my ‘Food is Medicine’ category things; i.e., when I need it for certain recipes and for a more tasty ROYO (brand) healthYful bagel, but I don’t rely just on this one product. I adhear to my cardio doc’s recommendations and also am open-minded to learning about new approaches like from this AWESOME group of like-minded healthyful types. Sincerely, Jan

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#54

Simple option would be to try 5mg. If still issues consider 5mg every other day. The literature is weak on CoQ10 - 50 - 200mg, but clinically I have seen many do well. You may also consider checking a genetic marker test that may mean you are more prone to muscle issues and myopathy. Boston Heart checks for it I believe - SLCO1B1

Good luck.

1 Like
#55

As I have already posted vitamin E in the form of alpha-tocopherol is the culprit.
Let’s clear the air, tocopherol is not the same as tocotrienols. Tocopherols are unsaturated while tocotrienols are unsaturated.

I can find no literature saying delta tocotrienols have the same negative side effects. In fact quite the opposite and

Several reviews discuss the anticancer and anti-inflammatory properties of delta-tocotrienol in skin and other tissues, suggesting it has beneficial effects on skin health rather than increasing skin cancer risk.

“Recent studies indicate that TTs provide important health benefits, including neuroprotective, anti-inflammatory, anti-oxidant, cholesterol lowering and immunomodulatory effects. Moreover, they have been found to possess unique anti-cancer properties.”

Link to full article and worth reading if you are interested in the ant-cancer properties of tocotrienols:
https://sci-hub.se/https://pubmed.ncbi.nlm.nih.gov/30652648/

2 Likes
#56

Interesting! I wonder if a SLCO1B1 genotype would be helpful in convincing a doctor (or insurance company) that someone is statin intolerant and in need of alternative treatment

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#57

Using one of the other options available due to intolerance seems reasonable. Using a lower dose and water soluble statin with higher dose Co Q10 was a strategy talked about at some conferences, but this may be out of date or disproven.

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#58

Can anyone tell if Berberine is safe to use with Rosuvastatin (2.5 mg) ?
ChatGPT:

"When considering the combined use of berberine and rosuvastatin, caution is advised, even though rosuvastatin is not significantly metabolized via the CYP3A4 enzyme. Berberine may still affect rosuvastatin’s action through different mechanisms, such as impacting the liver or altering the absorption and distribution of the drug in the body.

Other mechanisms: Berberine can influence other drug metabolism pathways, like transport proteins (e.g., P-glycoprotein), which could affect rosuvastatin levels in the blood. This could theoretically enhance rosuvastatin’s effects and increase the risk of side effects, even though CYP3A4 is not a major factor."

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#59

If you have trouble with a statin, try another one. It worked for me and now I have no side effects. I switched to Atorvastatin Lipitor.

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#60

Atorvastatin metabolized via the CYP3A4 enzyme, so it is not recommended for use with berberine.

1 Like