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maybe the units in the Hollenberg et al. article are wrong.

Or maybe your Lacueva et al  analysis is wrong.

The Hershey Co. funded study  cited above shows non-alkalinized cocoa powder yielding 30mg/g flavanols. (see posted graph),  close to the Comer Lab  Navitas numbers posted by Ron Put.

And look at the 2014 Consumer Lab test results for various cocoa/cacao powders with flavanol content well over 20 mg/g  posted here:

https://www.crsociety.org/topic/11013-cadmium-contamination-in-cacao-products/?page=3&tab=comments#comment-29455

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that quantity would surely fall into the toxicity domain. 

But in terms of flavanols,  900mg/day has been used in studies such as the one cited by Dean Pomerleau (funded by Mars Co.!) , which I linked to above.

Dean Pomerleau  Posted March 27, 2016

Here is a new study [1] posted by Al (thanks Al!) showing the benefits of cocoa flavanols on vascular stiffness. Once again it looks like chocolate is good for you, at least if not taken with too much dairy or sugar...

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[1] Impact of cocoa flavanol intake on age-dependent vascular stiffness in

healthy men: a randomized, controlled, double-masked trial.

 

Heiss C, Sansone R, Karimi H, Krabbe M, Schuler D, Rodriguez-Mateos A,
Kraemer T, Cortese-Krott MM, Kuhnle GG, Spencer JP, Schroeter H, Merx MW,
Kelm M; FLAVIOLA Consortium, European Union 7th Framework Program.
 

Free full text:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4444618/
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4444618/pdf/11357_2015_Article_9794.pdf

Abstract

Increased vascular stiffness, endothelial dysfunction, and isolated systolic
hypertension are hallmarks of vascular aging. Regular cocoa flavanol (CF)
intake can improve vascular function in healthy young and elderly at-risk
individuals. However, the mechanisms underlying CF bioactivity remain
largely unknown. We investigated the effects of CF intake on cardiovascular
function in healthy young and elderly individuals without history, signs, or
symptoms of cardiovascular disease by applying particular focus on
functional endpoints relevant to cardiovascular aging. In a randomized,
controlled, double-masked, parallel-group dietary intervention trial, 22
young (<35 years) and 20 elderly (50-80 year) healthy, male non-smokers
consumed either a CF-containing drink (450 mg CF) or nutrient-matched,
CF-free control drink bi-daily for 14 days. The primary endpoint was
endothelial function as measured by flow-mediated vasodilation (FMD).
Secondary endpoints included cardiac output, vascular stiffness, conductance
of conduit and resistance arteries, and perfusion in the microcirculation.
Following 2 weeks of CF intake, FMD improved in young (6.1±0.7 vs. 7.6±0.7
%, p < 0.001) and elderly (4.9±0.6 vs. 6.3±0.9 %, p < 0.001). Secondary
outcomes demonstrated in both groups that CF intake decreased pulse wave
velocity and lowered total peripheral resistance, and increased arteriolar
and microvascular vasodilator capacity, red cell deformability, and
diastolic blood pressure, while cardiac output remained affected. In the
elderly, baseline systolic blood pressure was elevated, driven by an
arterial-stiffness-related augmentation. CF intake decreased aortic
augmentation index (-9 %) and thus systolic blood pressure (-7 mmHg;
Clinicaltrials.gov: NCT01639781). CF intake reverses age-related burden of
cardiovascular risk in healthy elderly, highlighting the potential of
dietary flavanols to maintain cardiovascular health.

Edited by Sibiriak
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Mccoy,  recall the Miller et al. 2008 study (funded by Hershey Co.)  discussed previously  in your Kuna thread:

Impact of alkalization on the antioxidant and flavanol content of commercial cocoa powders.

 

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[...]natural, nonalkalized powders had the highest ORAC and total polyphenols and flavanols (including procyanidins). These chemical measurements showed a linear decrease as the extractable pH of the cocoa powder increased. Likewise, the flavanol monomers, oligomers, and polymers all showed a linear decrease with increasing pH of the final cocoa powder. When brown/black cocoa powders were compared to red cocoa powders, similar decreases in flavanols were observed with increased alkalization.  The average total flavanol contents were 34.6 +/- 6.8 mg/g for the natural cocoas, 13.8 +/- 7.3 mg/g for the lightly processed cocoas, 7.8 +/- 4.0 mg/g for the medium processed cocoas, and 3.9 +/- 1.8 mg/g for the heavily processed cocoa powders.

 

And hot of the Al Pater press,  a new meta-analysis (funded by Nestlé):

Dose-response relationship between cocoa flavanols and human endothelial function: a systematic review and meta-analysis of randomized trials (2019)

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An inverted U-shape relationship can be seen between total flavanols, (−)-epicatechin, and (+)-catechin with FMD, with a maximum vascular effect for 710 mg total flavanols (FMD 2.5%), 95 mg (−)-epicatechin (FMD 3%) and 25 mg (+)-catechin (FMD 2.5%).   

A physiologically relevant effect size of 1% increase in FMD could be achieved with doses ranging from 150 to 1000 mg of total flavanols, 40 to 140 mg of (−)-epicatechin, or 15 to 38 mg of (+)-catechin.

The curve for total flavanols without (−)-epicatechin depicted a different shape, suggesting that (−)-epicatechin content could be responsible for an important part of the relationship with FMD. Altogether, the results indicate that the (−)-epicatechin dose in the different interventional products plausibly drives the biological effect over the vasculature.

 

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Acute clinical trials demonstrating improvement in FMD outcomes with other high-polyphenol-containing foods described an inverted U shape relationship similar to that observed with cocoa polyphenols in this analysis. For instance, single consumption of several doses of blueberry drinks (from freeze-dried powder) showed a dose response with a maximum effect at 766 mg of polyphenols.39 Higher doses containing 1278 or 1791 mg of polyphenols did not show a higher impact on FMD values. Another study with different doses of cranberry juice demonstrated an improvement on FMD.40    An inverted U shape was observed with the dose containing 1238 mg of total polyphenols being the most effective.

 The idea that there is an optimal dose range of bioactives that would result in an optimal and physiologically relevant health effect could have large consequences for future dietary recommendations. In addition to the notion that higher concentrations
do not always bring more benefits
, the seasonal variation and the influence of processing on the polyphenol content in flavanol-rich foods could have significant impact on the health benefits that may be expected from the consumption of these foods. It is all the most important since, contrary to micronutrients (e.g. vitamins and minerals), these bioactives are not stored within the human body.

 

Edited by Sibiriak
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Sibiriak, of course with all the other overwhelming evidence, probably the Lacueva et al. study is wrong, as I myself seem to have tacitly acknowledged a while back. But I do not remember all things I wrote, since I write so much during my work. The hard drive in my brain starts to be clogged. Need an external one!!

Also, the 900 mg/d refers to (-)-epicatechin (do I remember well?) and, adopting a 2/3 conversion factor, it would mean 1350  mg/d flavanols, which would mean, at 30 mg/g, about 45 g unprocessed cacao powder per day, a much easier quantity to eat.

Also, it's weird that the Lacueva et al. study, which seems so meticulously prepared with a wealth of analytical data,  is one order of magnitude lower.

Edited by mccoy
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3 hours ago, mccoy said:

Also, the 900 mg/d refers to (-)-epicatechin (do I remember well?) and, adopting a 2/3 conversion factor, it would mean 1350  mg/d flavanols, which would mean, at 30 mg/g, about 45 mg unprocessed cacao powder per day, a much easier quantity to eat.

I think your calculation should be 45 g cacao per day.

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w

12 hours ago, mccoy said:

Also, it's weird that the Lacueva et al. study, which seems so meticulously prepared with a wealth of analytical data,  is one order of magnitude lower.

After a little thinking, it is all too reasonable to believe that, when analyses cite flavanols concentrations, they often imply all the flavanols group (total flavanols), which includes not only the single-molecule monomers (catechins, epicatechins) but also the dimers and higher-order molecules. There is a clear reference in regard in the wikipedia page:

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The single-molecule (monomer) catechin, or isomer epicatechin (see diagram), adds four hydroxyls to flavan-3-ol, making building blocks for concatenated polymers (proanthocyanidins) and higher order polymers (anthocyanidins).[1]

So, the flavanols would refer to the whole amount of monomers and polymers, whereas the term (-)-epicatechin refers to the single monomer-stereoisomer.

When lacueva et al. cite 'flavanols', they actually mean flavanol monomers, since they only analyze catechins and epicatechins.

Whereas, when the 900 mg/d epicatechin quantity is cited, that rises some doubts and perhaps is referred to total flavanols instead. Evidently, in the analytical practice, sometimes it is common to treat polymers as the equivalent amount of monomers. But biologically it is not the same, since we know that the monomers seem to be the most bioactive molecules. In a few words, it seems that it would be more useful to cite the epicatechin content of cacao rather than the total flavanols.

On the other side, if the proprtions between monomers and polymers remain more or less constant, then we may use the terms interchangeably.

Before being sure of the above I may have to re-read all the cited studies. Presently, I'm inclined to believe that the Kuna indians ingested an average of about 45 grams of unprocessed cacao powder per day, quantity which contains about 900 mg of total flavanols and about 90 mg of (-)-epicatechin.

45 grams of unprocessed cacao powder, given its pungency is not a small amount, but it is not an unreachable quantity, especially if added to other products. I myself have reached such quantity on occasions, although presently I'm more in the region of 30 grams per day.

Edited by mccoy
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  • 1 month later...

"... The lipids in cocoa butter, for

example, are not as effi ciently or as rapidly absorbed

as those in other vegetable fat because of the rather

complex molecular confi guration of these fatty acids in

cocoa triglycerides, which slows the time for overall

metabolism and, in particular, slows intestinal absorption

[4, 5] .

With respect to the consumption of cocoa

butter and its effects on serum lipids, the slower rate

of absorption of the triacylglycerides in cocoa butter

and the high polyphenolic content in cocoa actually

have a salutary effect. In humans fed cocoa, plasma

LDL cholesterol, oxidized LDL (so - called bad cholesterol

components), and apo B (an important lipoprotein

polypeptide critical to LDL function) are decreased,

while plasma HDL cholesterol (so - called good cholesterol)

is increased [6 – 8] ."

http://cms.herbalgram.org/heg/volume9/files/Chocolate_Appendix10.pdf

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