Monthly Archives: August 2013

Vitamin E and the Alzheimer’s Connection

Vitamin E and the Alzheimer’s Connection

Reference:  Mangialasche Neurobiol Aging

Vitamin E, in it’s alpha-tocopherol form has been a bit of bust as a supplement to prevent aging related cognitive decline.  That has been a big disappointment too.  It didn’t work with heart disease (least week) and it made prostate cancer worse, (two weeks ago).  But we keep trying because Vitamin E from food sources has been shown to slow down mild cognitive decline and has been inversely associated with Alzheimer’s disease.  What gives?

It’s the same old story you have heard for the last two weeks so the pattern should feel familiar.  When you look at all the Vitamin Es, you find that there are 8 of them, four in the tocopherol family and four in the trienol family.  Dr Mangialasche reviewed a Swedish and a Finnish population against all the Vitamin Es, including the tocotrienols.  In his study he found that gamma-tocopherols was the most protective in the Finnish patients, while the Swedish study showed that total toco and trienols reduced Alzheimer’s risk as much as 50%.  He calls for more research to tease out the protective effect that we find from the whole family of E’s compared to simply alpha-tocophreol.  But it is clear that a single one won’t do the work.  You need the whole mix of the rich family, and that’s what you get from whole foods.

Another way to do aging research is to examine what difference chemicals do to nematode worms that are very simple creatures.  Whether this research extends to humans is another question, but it is interesting for basic science questions.  Nematode worms only live 3 weeks so you can get a pretty rapid turnaround in research questions.  Their immune defense degrades rapidly and they get invaded by opportunistic bacteria.  All in 3 weeks.  Gamma tocotrienols extends their life span by markedly increasing their defense to infection.  Alpha tocopherol, classical Vitamin E, blocks any improvement.  Again, another example of the classical simply Vitamin E causing a problem by blocking the other family members.

In nature, there is likely going to be some utility to the blocking effect of Alpha tocopherol.   But right now, it’s the major Vitamin E that’s being studied.  We see a positive effect of Vitamin E when we have the whole family, all 8 of them, combined. We see a net negative affect when we give a supplementary unbalanced amount of just the single alpha-tocopherol.  What’s a person to do?

WWW.   What Will Work for Me?  I’m seriously thinking about starting to take Vitamin E again, but just as the toco-trienol form.  That is the form that we seem to see the most protective effect on heart disease, cancer and Alzheimer’s when you put the sum of them all together.  And that’s likely the form we have lost the most from our diets when we stop eating whole foods in balance, that are freshly prepared and eaten from local sources.  The story is still to play out and I look forward to seeing more meaningful research.  But I’m not throwing out the idea that the Vitamin E’s are possibly valuable.  My old bottle of alpha-tocopherol – that I threw out.  You should too.

Pop Quiz

1.  In a Swedish study, the use of the combined Alzheimer’s was associated with as much as a 50% reduction in Alzheimer’s risk.  T or F

True.  Interesting!  Not proof but intriguing.

2.  Nematode worms have a protective effect from infections with Vitamin Es.   T or F

True

3.   Research on nematodes translate strongly to humans? T or F

False.  They are handy because they live a very short time and help us sort our some basic physiology, but can hardly be taken as proof.  Very interesting place to start, but lots more real work needs to be done.

4.  You are likely better off getting your Vitamin Es from whole foods such as nuts and whole grains rather than an alpha-tocopherol supplement.

Bingo.

5.  If you take any supplement of Vitamin E, make it the gamma – delta toco-trienol.

Double Bingo.

Vitamin E: The Gamma Delta (γ,δ) tocotrienol and Cancer Connection

Vitamin E: The Gamma Delta (γ,δ) tocotrienol and Cancer Connection

Reference:  SELECT Trial and Pancreatic Cancer

As we mentioned last week, Vitamin E really has two families, each with four members (alpha, beta, gamma and delta in each).  The SELECT trial looked at the effect of alpha-tocopherol on prostate cancer and found a 17% increase.  Ouch.  But we also know that alpha (α) tocopherol directly inhibits gamma-delta (γ,δ) tocotrienol’s effective cholesterol lowering ability.  α-tocopherol also gets absorbed first, and blocks the beneficial effects of γ,δ tocotrienols.   Hence, one might ask, is there a beneficial effect of the γ,δ tocotrienols on cancer – drawing on the opposing effects of  those Vitamin Es compared to the one that was studied in the SELECT trial?

The answer may be quite markedly yes!  Dr Husain in the Journal Mol Can Ther in 20011 showed that δtocotrienol markedly inhibits pancreatic cancers through a variety of mechanisms, mostly the inhibition of NFκB and encouraging natural programmed cell death.  Phase One trials with Dr Malaga at the Mottiff Cancer Center at the University of Southern Florida have now been completed using up to 3200 mg a day ofδ- tocotrienol  with no toxicity, while at 200 mg increased cell death was noted in cancer cells from the δtocotrienol. Pancreatic cancer is particularly wicked because it has only a 5% 5 year survival and current detection methods are weak.  Dr Malafa has been able to show that great levels reach the pancreas with oral dosing and you get inhibition with few side effects.  Compare that to traditional chemotherapeutic agents and you have an attractive adjunct.

How did the SELECT trial go wrong?  Not sure but a Dr Campbell has looked at the SELECT trial and then compared prostate cancer cell line viability in culture media and shown that γ,δ tocotrienols potently reduce prostate cancer cell growth while (α) tocopherol hardly does.  It appears that the SELECT trial might have used the wrong Vitamin E.  Malviya has published a recent study showing potent γ tocotrienol effects with breast cancer, again through inhibition of pathways that encourage the cancer cell to grow (in this case, the PPAR system which is all about transcribing genes.

It appears to my reading that the Vitamin E connection to cancer is not yet resolved. The (α) tocopherol SELECT study looked at just one, the most common and abundant Vitamin E that suppresses and blocks some of the others.  Taken in isolation, it caused trouble, just as you might expect now that we know it blocks the tocotrienols uptake and action.

WWW. What Will Work for Me.  If I had prostate or breast cancer, I would be taking the γ,δ tocotrienols at around 200 mg a day.  Then, the question arises what we should do if we are adults over age 40, most of whom have islands of “precancerous” breast or prostate cancer cells within us?  Hmmm.  If it slows down cancer when it’s visible and clinically active, wouldn’t it also work when it’s microscopic?  We don’t have that research.  The volume of pills I’m taking might get a bit bigger.  Or should I just eat lots of beautiful vegetables and fruits and nuts and whole grains. That’s where these wonderful nutrients come from.  Less ice cream, where there isn’t any.

Pop Quiz

1.  The SELECT trial took the alpha form of the tocopherol side of the E family and found a 17% increase in prostate cancer.

Yupp!  Big disappointment and huge scare for all of us who had been taking Vitamin E.

2.  You can’t just say Vitamin E prevents cancer because Vitamin E is really two families, each with four members, and they seem to have different effects.

That’s it to the T.  The Tocotrienol family seems to be blocked by the tocopherol family, and has somewhat opposite effects.

3.  If you had breast cancer or prostate cancer, taking a supplement of extra gamma, delta Vitamin E might be a good idea?

I would think so.  Sure seems effective in a petri dish and has little to no apparent toxicity.

4.   I’m going to pay a bit more attention to how many nuts and bright colored foods I eat so that I get more natural sourced vitamins.

Nice plan.

What do You Know about Vitamin E?

What do You Know About Vitamin E?

Reference:  Second International Symposium on Tocotrienols. April 2012

There has been a fair amount of publicity in the last year or two regarding Vitamin E as being a problem.  In particular, the HOPE studies showed the Vitamin E did not really help heart disease or cancer in almost 10,000 patients followed for 7 years in a randomized trial.  In fact, it appeared to cause more heart failure.  That was discouraging because there had been a lot of anticipation of the results. The basic science of Vitamin E and its congeners is pretty interesting, and the negative results were pretty discouraging. What happened?

Here is the nugget of what “went wrong”.  The studies used alpha-tocopherol.  That is one of 8 vitamin Es.  Did you know there were 8 different Vitamin Es?  And that they come from two distinct families?  There are four in each family, apha, beta, gamma and delta.  The trienols are also Vitamin Es but act quite differently.  When we eat whole foods (nuts, grains, vegetables), we get combinations of them. When you do a study of just one, you get a marked imbalance and  lose the beneficial effect of the family.

The research on Vitamin E – tocotrienols family, the “other” vitamin Es have been sparking imaginative research from around the world in the last 3 years.  In particular, the “trienol” family has sparked lots of interesting results.  For example, the gamma and delta forms of the tocotrienols have been shown to have the exact opposite effects of adhesion molecule in bench research models of atherosclerosis.  (Rabbits with heart disease).  The stuff given to humans for heart research, alpha tocopherol, makes trouble, whereas the gamma-delta tocotrienols do the exact opposite: they inhibit adhesion of white cells to blood vessel walls.

Animal models also showed a 50% reduction in cholesterol levels with tocotrienols.  That’s pretty remarkable.  The mechanism for this is understood now in the down-regulation of the very beginning of the cholesterol pathway.

The problem arises in our own bodies.  We actually have a bias towards absorbing alpha-tocopherol, and it inhibits the action and absorption of the gamma-delta tocotrienols.  Eating mixtures of Vitamin Es shows that when you have more than 25% alpha tocopherol, you don’t get any cholesterol lowering effect.  If you have less than 10%, you start getting stronger and stronger cholesterol and antiinflammatory effects.

By itself, alpha tocopherol can be shown to increase cholesterol, increase the breakdown and metabolism of prescription medications, increase blood pressure and decrease bone mass.  These are all lousy, unwanted side effects.  How did we end up studying the alpha tocopherol form to the exclusion of all the others?  Heavens knows!  But it’s time to separate out the two from each other and begin to recognize that the complexity of our human diet and metabolism is far beyond what we first imagined.

WWW. What will work for me?  I need to understand the gamma-delta family of the tocotrienols.  They sound like they have a lot of promise.  So, more next week.  For now, hold the skepticism about how awful Vitamin E might be and realize that we have several cousins in the family.  And not every one is a Black Sheep.

 

Pop Quiz

1.  Alpha tocopherol has been found to have serious negative side effects without much positive benefit in good randomized controlled trials with heart disease.  T or F

Yup.  Disappointing but quite true.  And more heart failure to boot.

2.  The Vitamin E family has 8 members, four in each half with alpha, beta, gamma and delta members in each half?  T or F

That’s it.  8 cousins but not 8 brothers and sisters.  The Tocotrienols are quite different than the tocopherols.

3.   Alpha tocopherol is absorbed preferentially, and it appears to block some of the beneficial effects of the trienols.  T or F

That’s it.  That may be the reason we have such conflicting scientific research studies.

4.   Alpha tocopherol actually increases cholesterol?  T or F

True

5.   If I am taking Vitamin E, I probably should look at the bottle, and if it’s alpha-tocopherol only, I should stop.  T or F

Perfect.  Please stop now.