76 replies to this topic

[Michael]

Why do you take Pyroglutamic acid more often than Piracetam? It seems that there are more studies demonstrating the safety of Piracetam than there are of Pyroglutamic acid.

Yes, but pyroglutamate is an endogenous metabolite, while piracetam is a xenobiotic.

Would cognac have the same, or some of the same benefits as wine? It should contain many of the same polyphenols despite the distillation process.

"Polyphenolic compounds [extracted] from Cognac induce vasorelaxation in vitro and decrease post-ischaemic cardiac infarction after an oral administration [in rats]" (PMID 15147285). ""Oral administration of polyphenolic compounds from cognac decreases ADP-induced platelet aggregation and reduces chronotropic effect of isoprenaline in rats." (PMID 17705676). PMID:18052679: "Cognac polyphenolic compounds increase bradykinin-induced nitric oxide production in endothelial cells." Despite all of that evidence on endothelial function, PMID 18522727 found that "Cognac [100 mg phenolics per 2.4 dL (~1 C) serving] increased plasma antioxidant capacity, but it had no effect on coronary circulation in healthy young men." And viveutvitas: "Moderate consumption of red wine, but not gin, decreases erythrocyte superoxide dismutase activity [in] a randomised cross-over trial" (PMID 19819677).

You're assuming IAC that polyphenols are the "health-giving ingredient" in wine -- a reasonable assumption, but far from established -- and that sheer quantity of polyphenols does the job. AFAIK we have no health outcome data even to show that red wine (high-phenolic) is better than white (low-phenolic), and none either way on cognac vs. wine or other spirits.

Stick with wine, and go with red just in case.

Edited by Michael, 25 August 2012 - 04:22 PM.

[maxwatt]

...
You're assuming IAC that polyphenols are the "health-giving ingredient" in wine -- a reasonable assumption, but far from established -- and that sheer quantity of polyphenols does the job. AFAIK we have no health outcome data even to show that red wine (high-phenolic) is better than white (low-phenolic), and none either way on cognac vs. wine or other spirits.

Stick with wine, and go with red just in case.

I already do.

[cheezeweezel]

Stick with wine, and go with red just in case.

Fortunately, red is ever so much more pleasant than white, so this is easy advice.

But I have a question - I note that you (MR) take both zinc and iodine supplements with meals. I have repeatedly read that absorption of zinc/iodine/(other minerals?) is better between meals, to avoid both phytate and competition from the absorption of other minerals. Intra-meal supplementation has been my practice.

Is it true that you take them with food? If so, is that purposeful?

- cw

[Sillewater]

Does anyone, BTW, have decent data on how much an oxygen barrier a softgel provides? I drove myself half-nuts trying to dig up an answer t this some months back ....

J Pharm Sci. 1975 May;64(5):851-7.
Soft gelatin capsules II: Oxygen permeability study of capsule shells.

Hom FS, Veresh SA, Ebert WR.

Abstract

A method is reported for studying the effects of several factors at room temperature on the oxygen permeability of soft gelatin capsule shell films. The method involves the use of a permeability cell assembly and the spectrophotometric determïnation of oxygen with an alkaline pyrogallic acid solution. Factors investigated were relative humidity, plasticizers, equilibrium water, an insoluble additive, and film thickness. Results from the effects of film thickness and oxygen partial pressure correlated well with the permeability equation. For greatest stability of encapsulated oxygen-labile materials, it is recommended that the soft gelatin capsule shells be prepared with a low plasticizer concentration and that the finished capsules be stored at low relative humidity.


I don't have access to it but pg 19 on this document:
PMID: 1151660 [PubMed - indexed for MEDLINE]
http://capsugel.com/...nd-tomorrow.pdf

From what I read soft-gels are more oxygen permeable then hard shell.

The best data I can find is pg 3
http://www.daido-che.../pdf/pova-e.pdf

Table 1 Results of the oxygen permeability test
Film Oxygen (mol/m2∙sec∙Pa)
Type R 1.80 ´ 10-15
Type F 3.00 ´ 10-15
Gelatin 3.35 ´ 10-6
HPMC 8.13 ´ 10-4
Measuring method; manometric visual determination (ASTM D1434)
Measurement condition; 23℃, Film thickness; 100µm

From another site:http://www.jsppharma...ge=3&No=1401410

One basic difference exists between the hard and soft gelatin encapsulation processes. In the hard gelatin capsule process, the capsule is pre-fabricated and supplied empty, whereas in the soft gelatin capsule process the encapsulation and filling take place simultaneously. The moisture content of the gelatin/plasticizer mass at this stage can be around 50%, the equilibrium moisture level only being reached after several days storage on trays. It is conceivable that this is the most critical period during which migration and degradation of moisture sensitive drugs, which are readily soluble in glycerol, can occur.
Hom et al. reported that the oxygen transmission rate of a soft gelatin capsule film decreased with the level of glycerol in the film and also with the moisture content. As the hard gelatin capsule wall contains no plasticizer one may expect that the permeability of the hard gelatin capsule wall will be lower than that of a soft gelatin capsule. Cadé et al. reported on the smell assessment of soft and hard gelatin capsules containing the highly odorous products fish oil, valerian and garlic oil. Their results agree with the conclusions of Hom et al. , in that the permeability of the gelatin shell without plasticizer was found to be lower than that of the soft gelatin capsule with plasticizer. This higher permeability could have consequences for oxygen sensitive drugs filled into soft gelatin capsules.

[Sillewater]

http://www.qualicaps...cal/lineup.html


http://www.pharmatut...psules?page=0,2

[kismet]

I am reviewing fructose and just wondered "how much fructose is in an (almost) perfect CRON diet?"

59g of sugars, mostly from fruits I figure? (or the sheer volume of other stuff?) I can only guess 30-40% of it is fructose?

Edited by kismet, 07 April 2013 - 12:31 AM.

[Michael]

I note that you (MR) take both zinc and iodine supplements with meals. I have repeatedly read that absorption of zinc/iodine/(other minerals?) is better between meals, to avoid both phytate and competition from the absorption of other minerals. Intra-meal supplementation has been my practice.

Is it true that you take them with food? If so, is that purposeful?

Determining whether Zn supplements (let alone specific Zn forms) are better absorbed with or without food is a bit tricky, because there is a meal-induced depression of serum Zn, which confounds the results of simple comparison studies of pills taken on an empty vs. full stomach. I am reasonably convinced that it is at least not meaningfully worse to take it with meals than without, unless you're an impoverished Iranian living almost entirely on unleavened whole-grain wheat bread -- and, after all, our dietary Zn (whence comes all the DRI info an epidemiology) comes in food.

As I've said many times before, bioavailability is largely a bugaboo. If I were worried about low absorption, I could just take more.

Does anyone, BTW, have decent data on how much an oxygen barrier a softgel provides? I drove myself half-nuts trying to dig up an answer t this some months back ....

[Sillewater helpfully digs up some data]

Thanks Sille!

I am reviewing fructose and just wondered "how much fructose is in an (almost) perfect CRON diet?"

59g of sugars, mostly from fruits I figure? (or the sheer volume of other stuff?) I can only guess 30-40% of it is fructose?

Most of the sugars actually come from vegetables (with the caveat that I mean 'vegetable' in the culinary sense, to include eggplant, peppers, etc, which are botanically speaking 'fruits' — there being no such biological thing as a 'vegetable', and 'fruit' being both a culinary and a botanical category): my diet isn't particularly high in culinary 'fruit,' and less so after cutting out the pom juice (if you want to count that as fruit) last fall.

The new online COM now does let you track fructose. My current diet contains ~13.5 g/d, plus 3.9 g sucrose (so an additional 2 g or so of fructose). The pom juice previously added an extra 5.3 g free fructose and no sucrose.

These numbers should be taken as low, as many foods in the USDA database and even more 'custom' foods in the COM database have no data on specific sugars. And, many CR folk consume substantially more fruit than I do (notably, many positively gobble berries).

Edited by Michael, 17 April 2013 - 12:05 PM.

[kismet]

It's kind of funny. I was fooled by fructose research again. Recent evidence on fructose & pancreatic cancer made me think there now might be a legit reason for "fructose bashing". But the issue really does not seem that worrying on a regular diet nor is the evidence as strong as it first seemed.

Edited by kismet, 12 April 2013 - 03:02 PM.

[Andey]

It's kind of funny. I was fooled by fructose research again. Recent evidence on fructose & pancreatic cancer made me think there now might be a legit reason for "fructose bashing". But the issue really does not seem that worrying on a regular diet nor is the evidence as strong as it first seemed.

Is it your blog ?
I bookmarked it .I like the overall style of articles, moderately scientifical, well put together )

[Fredrik]

I see that you supplement with up to 4 g of beta-alanine daily. What do you think of this recent study that showed increased oxidation and decreased SOD-activity in rat brains with peritoneal injections of beta-alanine? A cause for worry? Study published April 26 2013:

http://www.longecity...-brain-of-rats/

Edited by Fredrik, 01 May 2013 - 12:32 PM.

[kismet]

I noticed you updated the OP. Thank you. Very interesting changes

Emerging strontium renalate CVD risk? Do you worry with citrate?
VTE risk has been documented*, apparently new pooled data finds increased MI risk.**

*http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2012/03/news_detail_001471.jsp&mid=WC0b01ac058004d5c1
**http://www.medscape.com/viewarticle/782483

And, yes, it's my blog.

Edited by kismet, 16 May 2013 - 07:52 PM.

[Brett Black]

Therefore, I went looking for a genuine concentrate of actual red wine that did not rely on high temperature or extraneous chemicals which might also alter the original mix, and which did not come from China or another country with high levels of industrial contaminants or shady business practices.

Have you considered de-alcoholised wine? The following site outlines various routine commercial methods to de-alcoholise wine which are carried out at low temperatures and apparently without added chemicals:
http://www.nonalcwin...lcoholic-drinks

[kismet]

...
Emerging strontium renalate CVD risk? Do you worry with citrate?
VTE risk has been documented*, apparently new pooled data finds increased MI risk.**

*http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2012/03/news_detail_001471.jsp&mid=WC0b01ac058004d5c1
**http://www.medscape.com/viewarticle/782483
...

Here some more detail for those who may be a little too lazy to follow the links. And that statement hot off the presses too. I eagerly await your well-informed reply.

PRAC recommends suspending use of Protelos/Osseor (strontium ranelate)
[NB: usual dose around 2g/d]

The European Medicines Agency’s Pharmacovigilance Risk Assessment Committee (PRAC) has recommended that Protelos/Osseor should no longer be used to treat osteoporosis.
In April 2013 the Agency had recommended restricting the use of Protelos/Osseor to reduce the risk of heart problems. These recommendations were the result of a routine benefit-risk assessment and it was also decided at the time that there was a need for a further in-depth review.

The PRAC has now conducted an in-depth review taking into account available data on the benefits and risks of the medicine. The Committee noted that for every 1,000 patient-years1 there were 4 more cases of serious heart problems (including heart attacks) and 4 more cases of blood clots or blockages of blood vessels with Protelos/Osseor than with placebo (a dummy treatment). In addition, Protelos/Osseor is associated with a number of other risks, such as serious skin reactions, disturbances in consciousness, seizures (fits), liver inflammation and reduced number of blood cells...

http://www.ema.europ...WC500159375.pdf

Edited by kismet, 10 January 2014 - 11:32 PM.

[Spherical Cow]

...
Emerging strontium renalate CVD risk? Do you worry with citrate?
VTE risk has been documented*, apparently new pooled data finds increased MI risk.**

*http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2012/03/news_detail_001471.jsp&mid=WC0b01ac058004d5c1
**http://www.medscape.com/viewarticle/782483
...

Here some more detail for those who may be a little too lazy to follow the links. And that statement hot off the presses too. I eagerly await your well-informed reply.

PRAC recommends suspending use of Protelos/Osseor (strontium ranelate)
[NB: usual dose around 2g/d]

The European Medicines Agency’s Pharmacovigilance Risk Assessment Committee (PRAC) has recommended that Protelos/Osseor should no longer be used to treat osteoporosis.
In April 2013 the Agency had recommended restricting the use of Protelos/Osseor to reduce the risk of heart problems. These recommendations were the result of a routine benefit-risk assessment and it was also decided at the time that there was a need for a further in-depth review.

The PRAC has now conducted an in-depth review taking into account available data on the benefits and risks of the medicine. The Committee noted that for every 1,000 patient-years1 there were 4 more cases of serious heart problems (including heart attacks) and 4 more cases of blood clots or blockages of blood vessels with Protelos/Osseor than with placebo (a dummy treatment). In addition, Protelos/Osseor is associated with a number of other risks, such as serious skin reactions, disturbances in consciousness, seizures (fits), liver inflammation and reduced number of blood cells...

http://www.ema.europ...WC500159375.pdf

Good find.

Is it useful to be supplementing it at a 6th of the therapeutic dose to start with? The vascular and neurological side effects are important considerations.

Might the Çelik et al. [1] study be relevant?

[1] A Çelik et al., Journal of Cell & Molecular Biology, 2011, 9, 27-35. http://jcmb.halic.edu.tr/pdf/9-2/4.pdf

Edited by Spherical Cow, 28 January 2014 - 07:41 PM.

[ralmcruz]

Hey Michael,

Can you think about making a updated version of this topic?

[Michael]

Hey Michael,

Can you think about making a updated version of this topic?

 

Done!  See my new 2017 supplement regimen — just in time for the Supplement Stack Competition! Warning: it takes forever to load ...

[Rocket]

No methylene blue???