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dante_cubit
Registered Member

Date Joined Dec 2004
Total Posts : 32

Posted 2/9/2005 1:57 PM (GMT -5)

On the following link, a representative of Advanced Orthomolecular Reseach offered the following critique of the LE mix:
http://www.imminst.org/forum/index.php?act=ST&f=6&t=5186&s=

"LEF makes very high-quality supplements. However, I'm afraid that I have to quibble with the formulation of many of them. The LEF mix contains many of the hazards common to multivitamins: enough retinol (preformed vitamin A) to roughly double your risk of fracture, unbalanced alpha-tocopherol levels high enough to drive out other E vitamers and increase your risk of all-cause mortality; high-dose niacinamide, which life extensionists should probably avoid due to the potential issue of niacinamide’s nullification of the potential anti-aging effects of sirtuins; hazardous (>20:1) zinc-to-copper ratio; putting green tea extract into the mix, even though green tea and its extracts inhibit absorption of various minerals; inclusion of a variety of ingredients (Such as sylimarin) with no proven safety or efficacy in normal, healthy humans; a dose of lycopene (3 mg) far below the 14-18 mg present in the diets of the high-quintile of the population, established by epidemiology for reduced risk of a variety of diseases; other, minor issues."

Any thoughts? I personally trust LEF's products more than AOR. The latter's seem to be overpriced, and they overexaggerate the drawbacks of conventional lipoic acid.

The vitamin A content of LE Mix is the US RDA.
The other tocopherols are offered separately in a softgel as their liquid state makes it difficult to add to tablets, capsules or powder.
The niacinamide issue is under consideration but a lot of people can't or won't tolerate niacin as a source of B3.
According to some nutritionists, an ideal copper to zinc ratio is 1:15. Many people are more deficient in zinc than copper, particularly those who drink tap water from copper pipes, and therefore need more zinc to attain this ratio. Some don't need to supplement with copper at all, and LE Mix is available without it for those who want it.
Many nutrients lessen the absorption of some minerals, including calcium, zinc, vitamin C, fiber and water. You can try taking everything separately if you have time.
Silymarin has been the subject of studies which have found positive results http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11735632 , as have been all of the nutrients in LE Mix. It would be a waste of Life Extension's resources to add a nutrient to Life Extension Mix for no reason. We are not aware of any safety issues in regard to the use of a prudent dose of silymarin.
Life Extension Mix is intended to supplement the diet with a number of nutrients found to be beneficial to human health. If one wants more lycopene, it is available separately or in other supplements. Considering the rapidity with which new phytonutrients are being discovered, if every nutrient ever found to benefit human health was present in Life Extension Mix in optimal amounts, one would be consuming many more tablets than 9 per day. - Moderator

Post Edited By Moderator (DDye) : 7/23/2005 12:17:54 PM (GMT-4)

zorba990
Registered Member

Date Joined Jul 2004
Total Posts : 710

Posted 2/9/2005 5:15 PM (GMT -5)

I would like to see the magnesium oxide removed completely and replaced

with a better absorbing magnesium.

Peter46
Registered Member

Date Joined Mar 2001
Total Posts : 14

Posted 7/12/2005 12:25 PM (GMT -5)

I agree very much with the comment on high dose niacinamide in the LE Mix possiblly having a negative effect on sirtuins. I brought up this potential problem 1 year ago (June, 2004) with LEF. The answer was that my comments would be "filed" and should get management review. As of Feb, 2005 the issue is "under consideration." It's time to get a more specific answer from LEF, so I'll try again.

Basically, the problem is this - nicotinamide (aka niacinamide) is mentioned in the literature as a sirtiun inhibitor. The life-extending effects of CR are thought to be due to sirtium activation. And resveratrol is thought to work through the same pathway. So it would be ironic if you're CR or injesting extra resveratrol, just to have have it negated by too much niacinamide (LE mix conatains about 500% of RDA as niacinamide). I think this is potentially a big issue and should get more attention. Certainly one of the more biologically knowledgable board members of LEF could take a few hours to review the available literature and render a preliminary opinion.

preston
Registered Member

Date Joined Jul 2005
Total Posts : 2

Posted 7/23/2005 12:15 PM (GMT -5)

The theory of activation of sirtuins is based on yeast cell activity, not mammillian cells. Recent research shows that the shutting off of the sirtiun gene actually causes cell longevity in rats--much more closely related to humans than yeast.
http://lef.org/news/LefDailyNews.htm?NewsID=2484&Section=AGING

The reasons that resveratrol maintains all of its health benefits are unknown at present. It was theorized that resveratrol activates the sirtuin gene in mammals, but it is just as plausible that it has the effect of shutting it off, which in the case of rats (and hopefully humans) would be beneficial.

If indeed niacinamide was shutting off the same gene, the antiaging effect may be positive.

ajnast4r
Registered Member

Date Joined Jul 2005
Total Posts : 5

Posted 8/7/2005 8:49 PM (GMT -5)

OptiZinc does not interfere with copper absorbtion

http://www.interhealthusa.com/faqs/loptizinc_faqs.aspx#howisitdifferent

Peter46
Registered Member

Date Joined Mar 2001
Total Posts : 14

Posted 8/15/2005 6:01 PM (GMT -5)

After a couple of more tries to get a response out of LEF about their position and what they're doing to evaluate the "potential" negative impact of niacinamide that's in their mix I got the response below which simply cites a 2001 summary of a study (not the recent 2005 study on mice). And no "specifics" about what LEF is doing to address this issue. Since last year I've sent at least 4 emails on this subject and am yet to get one reply that makes me feel LEF is doing anything substantive on this issue.

******************************************************************************************
Guido,

Thanks for your response. I was aware of the 2001 article and study you mentioned.

Since sirtuin inhibition (or activation) by nicotinamide is potentially very important I was hoping that someone affiliated with LEF was taking a serious look at the relevant studies over the last few years in hopes of trying to sort out potential study flaws and arrive at a tentative conclusion as to what should be done with respect to supplementing with excess nicotinamide. The work I cited below is 2004 vintage by reputable institutions and scientists – they point to a conclusion that “seems” to contradict the 2001 study you cite. My concern is that taking too much Nico in the LE Mix will inhibit sirtuins, and that the older studies may have made flawed conclusions about what nico does. Clearly something is wrong with one or more these studies.

If LEF spent a little time searching the literature, a number of other more recent papers discussing sirtuins, NAD/NADH ratios and nicotinamide, beyond what I mentioned would be found. I would think that someone with the proper credentials to evaluate scientific studies of this nature could review these recent studies, and the older conflicting studies, in a fairly short time frame and draw some conclusions that would be at least as valid as some of the conclusions that LE has drawn about another sirtuin activator, resveratrol, which has been written about fairly extensively in LE mag

I hope LE Org takes the time to seriously evaluate this issue and at some point in the near future publish its findings, even if inconclusive. Failing that, consider a version of the MIX that provides something less than 500% of the RDA for nico until this issue is better resolved.

Thanks again. I hope to see something published soon.

Pete
--------------------------------------------------------------------------------

From: Guido Dominic [mailto:gdominic@lifeextension.com]
Sent: Tuesday, August 09, 2005 2:21 AM
To: pezzell@xtalwind.net
Subject: FW: LEF Advisory Questions/Comments

Hello Pete,

Thank you for contacting Life Extension. As you know, this is an ongoing concern and still being investigated with product development. Just an FYI for you, I was able to find another interesting article about nicotinamide that may shed some light.

Nicotinamide Induces Rejuvenation
In Human Cells

http://www.life-enhancement.com/LE/article_template.asp?ID=671

If any new information is released about our product, I will be glad to forward it to you ASAP.

Wishing you Maximum Health

Guido Dominic

LEF Health Advisor

--------------------------------------------------------------------------------

From: Pete Ezzell [mailto

ezzell@xtalwind.net]
Sent: Wednesday, July 13, 2005 4:51 PM
To: 'advisory@lifeextension.com'
Subject: LEF Advisory Questions/Comments

Information out of MIT (2004, Guarante) and the Albert Einstein School of Medicine indicates that nicotinamide “inhibits” the activation of mammalian sirtuins, an apparent negative result in terms of life extension as activation of sirtuins may be how calorie restriction works to extend live.

This issue has been brought to the attention of LEF in the past as nicotinamide is present in the LE mix at about 500% RDA (niacinamide = nicotinamide, LE uses the term niacinamide).

Can you tell what if anything LEF is doing to evaluate whether the MIX concentration of nicotinamide needs to be lowered, or how solid the evidence is, in your opinion, for the stated effect of nicotinamide?

Thanks,

Pete Ezzell

PS This is potentially a significant issue. LEF has published a lot about the effects of resveratrol and advocates using it’s product. Resveratrol also appears to work, in part as least, by the same sirtuin pathway. It would be ironic if we are negating the effects of resveratol or caloric restriction by ingesting too much niacinamide.

Ms.
Registered Member

Date Joined May 2003
Total Posts : 42

Posted 8/19/2005 5:32 PM (GMT -5)

"...The vitamin A content of LE Mix is the US RDA."

But it still has 5000 IU of A acetate, and women (like me) who are fighting osteoporosis don't dare take it. I remember this same discussion coming up several times over the last 2 years or so, but the formulation still contains a significant amount of A acetate. Is there some reason that LEF feels the A acetate needs to be there even with the 5000 IU of beta-carotene? Is the problem that in order to be called a "multi-vitamin," the mix required to have that much A acetate in it? Or are there benefits of A acetate that can't be gained from the carotenes for people who aren't worried about their bones?

Cindy

CB
Registered Member

Date Joined Aug 2005
Total Posts : 44

Posted 9/9/2005 12:44 PM (GMT -5)

The LEF "Two Per Day" vitamin/mineral tablets contain 4000 IU of Vitamin A as palmitate and 1000 IU of Vit A as beta-carotene. Perhaps a good choice for postmenopausal women concerned about osteoporosis?

In a risk/reward analysis one has to wonder if avoiding multi formulas due to Vit A content is a good tradeoff. By following a complete osteoporosis prevention protocol any negative effects of Vit A supplementation might be totally overcome. It is unlikely that the majority of women in the studies suggesting a relationship between Vit A and bone loss were doing all that can be done to prevent osteoporosis. In any case, the key would be to track bone density using the quantitative computed tomography (QCT) test. If this reveals a problem the Vit A containing product could be dropped but if no problems are revealed then you would have the benefits and convenience of using a quality multivitamin and peace of mind.

The question of whether there are "benefits of A acetate that can't be gained from the carotenes for people who aren't worried about their bones" is interesting but it is really the other way around. Beta-carotene potentially has benefits that vit A does not have although there are contradictory studies about these and ongoing research. The problem with beta-carotene as a source for Vit A is that the conversion to Vit A in the human body is complex and highly variable, particularly from food sources but also in supplement form. I don't know why vitamin manufacturers include both but it seems likely that this variable conversion of beta-carotene to retinol is one reason.

A good in depth article summarizing what is known about beta carotene is at . http://www.pdrhealth.com/drug_info/nmdrugprofiles/nutsupdrugs/bet_0032.shtml

CB

albedo
Registered Member

Date Joined Jan 2008
Total Posts : 754

Posted 12/20/2009 7:55 PM (GMT -5)

Even in the most recent Mix the niacinamide dose is still much higher (600% ? to be verified) than RDA and I still wonder how this copes with the problem of inhibition of sirtuins, thus lessening their longevity effect.

rizwan
Registered Member

Date Joined Dec 2005
Total Posts : 142

Posted 12/29/2009 9:17 PM (GMT -5)

One would expect that the LEF scientists would defend the formulation in the LEF magazine and on the website and acknowledge potential issues and knowledge gaps. However it seems that level of openness with the members does not exist yet.

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