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Another Day, Another Pill - 2012 Supplement Regimen

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#1 Michael

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Posted 10 February 2012 - 07:21 PM

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All:

First, please see my discl0sure here. I'd appreciate this fact not being discussed in open forum, as I value my privacy, but y'all should know.

Now:

I occasionally get requests for an update on my supplement regimen of 4 years ago and my supplement regimen of two years ago, and I'm now following thru'. Once again, I've done more removal of things as stuff has failed to pan out or suddenly appeared to be dangerous than I have in adding new stuff in, along with making a few changes (mostly reductions) in dose, and changing the forms of a couple of items. But things have indeed changed, so here is an update. (I documented some of the changes, and some of the reasons, as I went along in my 2009 regimen post op cit).

As background, please see this post about dietary supplement use in general; this kind of reasoning should inform everyone's judgements about what supplements to take, and why, for them as individuals. Note that I am much more wary about engaging in "Tier 3" speculation than I was back then, and indeed, nearly everything that was on that list at the time has been knocked off by subsequent evidence.

The most important thing you can do as regards all essential vitamins and minerals is to actually use nutrition software to get a handle on your actual dietary intake of these nutrients before deciding what to supplement, tho' this is less of an issue to the extent that your diet is (a) genuinely poor (& thus more likely to actually need 'everything' and not be overdosing on eg Mn, Cu, etc) and (b) you're not on CR (and thus have a lot of 'slop factor' and don't have the specific nutritional risks of CR folk). (Yes, ironically, health-conscious people actually have more need for caution in supplementation, because they often wind up on somewhat restrictive 'health food' regimens that limit the diversity of their nutrient sources, and because, as noted above, it's common for people eating quite well to get almost too much of some nutrients from diet alone, and then add supplements on top of that. Studies show, perversely, that the people who need vitamin supplements the most use fortified cereals the least -- and the converse). A 2-week representative COM crunch of my diet is appended; see also this detailed post on my quotidian diet). Do also make use of the relatively few reliable functional diagnostics for nutrient deficiency, such as serum 25(OH)D3, homocysteine, and MMA.

On this point, let me emphasize the logical corollary which I've spelled out repeatedly but that people keep missing: unless your diet is composed entirely of fries, Coke, and fast-food burgers with the lettuce, ketchup, and tomato thrown out, no one should be taking a full daily dose of any commercial multivitamin. You are absolutely guaranteed to get too much of many nutrients, and to create or exacerbate imbalances in others.

I should also emphasize the other corollary: this is a regimen for a very specific individual: a very healthy, young(ish) CR practitioner with an excellent diet (which I've analyzed extensively, to understand its weaknesses and "excessive" strengths -- see a representative week's average appended to this post). As the links above indicate, a person must customize hir regimen based on hir own diet, and also age, specific risk factors, existing diseases, etc.

So: the regimen (notes on WHY I take various things at the end, when it isn't obvious from the link or other grounds):

UPON WAKING (5 AM or before), w/ green tea 1/3 c pomegranate juice+ 2/3 C diet Dr. Bob [dropped fall 2012; see below]
1/2 tsp (~2.5 1.8 g) CreaPure Creatine monohydrate (do not buy commodity creatine! See below).
1 Prostaphil defined pollen extract

5:50 AM, with coffee green tea [switched fall 2012; see "Quotidian Diet" post]
1000 mg AjiPure L-Lysine
0.5 g Beta-alanine

6:30 AM, breakfast:
[I would be taking Provinols,if I could find them ...]
420 mg Phosphatidylcholine
250 mg Lactoferrin
15 µg vitamin B12 (1/6 of 100 µg tablet)
While scrubbing teeth: 1 drop per eye N-acetyl-L-carnosine eyedrops

10:30 AM, with green tea:
500 mg IP-6
500 mg Inositol (possibly synergistic to IP-6)

11:10 AM, with coffee green tea:
0.5 g Beta-alanine
Brain nutrient (rotating one of: 800 mg piracetam ( why?) (once/wk), pyroglutamate (500 mg, thrice/wk) and ALCAR (125 mg thrice/wk [dropped spring 2013 as a result of (36)])

11:50 AM, with green tea:
5001000 mg AjiPure L-Lysine, 500 mg arginine [See my reply to a question from viveutvitas on why I dropped the arginine] (no, these do not interfere with one another's effects for this application).

12:30 PM, lunch:
420 mg Phosphatidylcholine

750 mg taurine
30 mg CoQ10
15 mg Menatetrenone
1 mg Lithium (orotate -- do see note below!)
56 µg Iodine (1/4 of 225 µg, 6 d/wk)

4:30, with coffee green tea or other beverage:
500 mg IP-6
500 mg Inositol (possibly synergistic to IP-6)

5:10, with green tea or other beverage:
0.5-2.5 g Beta-alanine (higher dose when doing resistance training)
1 Prostaphil

5:50, with coffee green tea or other beverage:
1000 mg AjiPure L-Lysine (1.5 g arginine when doing resistance training)

6:30, dinner:
857 IU (average) vitamin D3 (as 1 x 1000 IU softgel, 6 d/wk)
750 mg taurine
15 mg Zn (citrate)
420 mg Phosphatidylcholine [Added 2012/02/14]

10 pm, bed, with green tea or other beverage:
0.5 g Beta-alanine
5 g AjiPure Glycine
314 mg Strontium (citrate)
750 mcg melatonin (as required)

Further on Rationales
Pomegranate juice: I want SOME source of relatively high-GI sugar without protein or fat to get glucose levels up first thing on rising, and for the possible benefit of taking creatine with a sugar source (tho' it's not at all clear that this is anything like enough glucose to meaningfully affect this, nor that the extra boost to tissue reserves as vs. water coadministration during the loading period is sustained with ongoing administration); I chose pom juice for the many promising-looking studies in disease states, tho' again the dose may be inadequate (studies typically use 1-2 C). Don't blow your bucks on POM Wonderful: Trader Joe's has it reasonably cheap, as does Georgian Nectar (a hard-to-find brand I sometimes find at a local Asian grocery store). I would "look" for brands that aren't syrupy or sickly-sweet, and still have some bitterness and residual granular material; Lakewood has the stuff genuinely fresh-pressed rather than from concentrate, which strikes me as likely preferable, but it's VERY expensive. My preferred brand at the moment is Langers Fresh Pressed (not from concentrate). Nixed the pom juice out of concern about starting my day off with a big blast of sucrose — fall 2012..

The diet Dr. Bob is 'cause I like it and it has zero Calories; it's cheaper and to my taste yummier than the brand name original. No, I am not worried about aspartame (or sucralose, for that matter) causing cancer or neurological disease. Indeed, the recent, much-hyped report of increased cancer in aspartame-dosed rodents (3) actually made me less nervous about aspartame: it (a) really didn't clearly show any increased cancer risk (they hyped up non-statistically-significant elevations in incidence of some cancers late in life, but also NS decreases in others), and indeed (b) reported identical survival curves between aspartame-treated and untreated animals (if anything, it looked like females given the highest dose lived LONGER on average than untreated animals); plus, there was massive mortality from inflammatory lung disease and other causes, showing that these people just can't raise healthy mice. Additionally, because aspartame has been on the market for a quarter century and is widely and selectively used, there's now been enough time for both additional direct human and animal research and decades of prospective epidemiology (4,5) showing no ill effects over a wide range of intakes in humans. If you were alarmed by a recent scary-sounding paper in an otherwise-respectable journal,(6) please see this post debunking the junk science on "Direct and indirect cellular effects of aspartame on the brain" by Humphries, Pretorius, and Naudé (5a). However, I am beginning to become concerned about the emerging evidence suggesting long-term dysregulation of glucoregulatory hormones and signaling related to artificial sweetener use, and have cut back quite substantially on consumption of soda and sweetening tea and coffee. This change dates to fall 2012. Later yet (June 2013): cut artificial sweeteners outside of solid food ingredients/condiments (and cut those back) in response to (37).

To read a thoughtful, non-paranoid, non-"it's-just-not-natural!" argument for caution by a reputable and careful scientist, I refer you to Devra Davis' excellent (and disturbing) Secret History of the War on Cancer.

Creatine, beta-alanine, ALCAR, taurine, zinc: I'm ovolacto for my quotidian diet, and am therefore somewhat low on these, and Vegetarian Booster has been discontinued. Plus, I found during a period that I briefly ran out of Veg Booster and had to buy these nutrients (at higher dose) individually, that I felt better on the higher ALCAR and creatine combined with the concomitant R(+)-lipoic acid (which last I took to compensate for the increase in carnitine and teh switch to ALCAR in particular); and, I actually exhibit symptoms of Zn deficiency when I don't, despite a fairly high dietary Zn, presumably due to high dietary copper. More on most of these below. Note that ALCAR, like free choline, can be metabolized into TMAO by gut bacteria ((37) and other references) and appears to promote atherogenesis even in persons with low LDL and other CVD risk factors.

Creatine: As noted, I'm vegetarian, and our intakes and serum levels are lower than omnivores' (from these three sources, it appears that typical omnivorous dietary intake is 1-2 g/d, and some of that will be unabsorbable due to cooking, unlike high-quality supplemental creatine), and trials seem to show that vegetarians'muscles and (on some tasks) brains work better when given a low-dose supplement(18). If you use creatine, insist on a supplement made using CreaPure (a branded raw material manufactured by AlzChem AG (fixed 2012-02-18 -- thanks sdxl) (formerly Degussa AG Trostberg; formerly SKW) but used in several different retail brands). Years ago, Dr. N..... at A0R had raised concerns about contaminants in other creatine manufactrers, but I never looked into it at the time as A0R wasn't marketing it and I wasn't taking it. A while back, however, I bought some creatine from a company that I generally consider to be quite reputable and from whom I often buy commodity-item supplelments, and was disturbed by its very bitter and (surprisingly) soapy taste. I called the company, who dug back thru' their QC procedures and retained sample, insisted that it was fine; I did some digging and found that there are indeed reasons for caution, as outlined in these two very good articles on creatine by Will Brink: "What's in your Creatine?" and "What's Really in Your Supplements? - An Update on Creatine"; see also Alzchem's CreaPure promotional materials. I proceeded to order some CreaPure-sourced creatine and was surprised that, for the very first time with any creatine supplement, the stuff had absolutely no bitter taste to it: the suspicious supplement had been the first one I'd ever used that had a soapy taste, but every creatine I'd previously used had a mild bitterness to it, which I'd thus assumed to be intrinsic to creatine itself, whereas it now seems it is rather the taste of some impurity. There is no direct evidence that dicyandiamide or dihydrotriazine is harmful -- but why anyone (let alone a life extensionist!) would knowingly put high (relative to likely dietary intakes) levels of organoleptically-detectable impurities of unknown toxicity into hir body to save a few dollars is beyond me.

Also, do read this sensible safety caution about the long-term effects of creatine supplement use (starting just after the paragraph on the effects of caffeine), much of which applies to many other supplements.

I originally thought 1/2 tsp of my creatine delivered ~2.5 g, as per the "Nutrition Facts" panel; upon being asked by bmdelaney, I weighed the stuff, and it's actually ~1.8 g. Annoying, but I'm actually OK with that, as it's closer to typical omnivorous dietary intake is, and thus errs on the side of safety.

Beta-alanine: I was previously taking carnosine, which is possibly anti-senescent cell, possibly anti-mitochondrially-mutant cell, and is deficient in vegetarian diet. However, I've now substituted beta-alanine, for which there is much better evidence of elevation of tissue carnosine levels (and, I happily anecdotally report, seemingly impressive muscle power gains, consistent with the surprisingly large number of clinical trials with the stuff, tho' this wasn't what got me interested originally). One thing to watch out for is the dose: bottle directions often suggest 2 g, 4 x daily, which is the final, ramped-up dose used in the trials; however, this is likely to cause you (as I shame-facedly admit, it caused me) maddening paraesthesia (pins and needles), as explained here. Instead, start at 500 mg 4 x daily, and work your way up as needed or desired; I only take a higher dose on days when I'm doing resistance training.

Prostaphil defined pollen extract: I have an idiopathic urinary urgency; definitely not BPH or bacterial prostatitis, conceivably related to alpha-adrenergic function. This is subjectively very helpful.

Iodine: Getting reliable information on iodine intake is very difficult. As a vegetarian, my intake is probably low, and I do consume a significant amount of cruciferous veggies, which inhibit iodine uptake by the thyroid. I'd strongly caution against using "sea vegetables" as a source, because iodine levels in same can be EXTREMELY high: in particular, kombu kelp can savage your thyroid gland (and see followup on kombu and thyroid risk). Moreover, unfortunately most iodine supplements are kelp-derived and high-dose -- and occasionally unreliable or contaminated with arsenic. The NOW supplement I link above serves my purposes well.

Menatetrenone: I have low BMD typical of natural- and CR-induced low BMI; this is a fracture risk factor, tho' not as much as would be routinely assumed and even diagnosed, because of my overall risk profile: see the new FRAX fracture risk assessment tool developed by the WHO. See also this post on how CR appears to protect bone against age-related decline in bone quality/microarchitecture, for which the available human evidence is now in support, or at least to which it offers no contradiction.(35) Menatetrenone seems promising for CR-related low bone mass, as the actual MASS of bone is constrained by low energy intake, whereas menatetrenone primarily appears to reduce risk by preseving QUALITY -- a more likely viable strategy.

Arginine and lysine: these have been found to be surprisingly effective in reducing AGE and AGE-induced complications of diabetes, especially in the kidneys but also apparently in the heart (6-12a). (13) was negative, but the measurement of AGE was in skin, which not be reached by a significant concentration of these nutrients (vs the heart and kidneys, thru' which they would of course travel in the blood when they're taken on an empty stomach) (tho' (11) did find reductions in hexosyllysine), and their conclusion was (reasonably) that "treatment may need to continue for more than 1 year before clinical status improves." [Edit: nixed the arginine, due to concerns raised by viveutvivas]. Sourcing: After first my creatine experience (above), I recently had a quite similar experience with Ajinomoto's AjiPure Glycine: the taste of their product is sweeter and 'cleaner' than any other brand I've used. Because I'm now consuming 3 g of lysine a day, and with the knowledge of the impurities underlying the bitter taste in commodity creatine, and in recollection of the tryptophan-related outbreak of eosinophilia-myalgia syndrome (EMS) in 1989, I've recently (late May 2012) switched from commodity lysine to Ajinomoto's AjiPure L-Lysine.

Provinols: the only authentic red wine concentrate, which I would take if I could find if I could find the darned stuff. Unlike the shaky-to-begin-with-and-now-disproven resveratrol hype, there is a quite solid body of epidemiological evidence of an association between a couple of glasses of wine a day and lower risk of a range of adverse outcomes, including total mortality and dementia. The epidemiology clearly indicates a U-shaped dose-response curve for alcohol consumption and heart disease, with the best outcomes associated with 1-3 drinks/d, and this extends to total mortality in meta-analysis(19); but when broken down into type of alcohol consumed, only wine lowers total mortality and dementia: beer or spirits lower CVD mortality, with no effect on total. (No, despite the use of these findings as a justification for resveratrol supplements, there is no epidemiological evidence favoring red over white). The benefits for total mortality reach a nadir at <1 drink/d for total mortality:


Figure 1. Relative risk of total mortality (95% confidence interval) and alcohol intake extracted from 56 curves using fixed- and random-effects models. From (19).

Wine consumption vs. total mortality. From (38).

However, my working hypothesis is that the climbing risk is due to the toxicity of alcohol per se, and that additional benefits might be available from higher intake of the component(s) of wine responsible for these benefits, without the extra Calories and toxicity of drinking the stuff. However, we don't know which component(s) of wine exert these effects, so we should aim for a supplement that is a direct concentrate of the same spectrum of bioactives in actual, fermented wine -- ie, not just resveratrol, nor the grape-seed and/or -skin extract that is often mislabeled "wine extract," and whose polyphenol mix is actually quite different from that in wine, due to complexation and biotransformation that the grapes undergo during fermentation. Seppic in France has done a great deal of work in characterizing these, and still the surface is only barely scratched and we don't know what might do what.

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.

I first hit on Provinols, which is a pioneering product in this field, but unfortunately it is damned near impossible to get in the Americas, except in low doses and mixed in with other junk. (Europeans and Turks may be able to get it, however). I was at one time convinced of the authenticity of a product called Wine Rx, but they subsequently failed to document their claims on composition, and moreover, it seems to go vinegary and weird in well less than a year -- not surprising perhaps granted that it was only a 50% extract. So, I wait glumly for the Real Deal.

Phosphatidylcholine: Replaces citicoline and free choline supplements, which may promote atherosclerosis. (Citicoline and carnitine also generate TMAO, NB). Note that phosphatidylcholine is only 13% free choline by weight, so eg 420mg of phosphatidylcholine is only ~55 mg free choline (thanks Sillewater!). June 2013: the COM crunch below indicates ~250 mg choline/d from diet; more recent COM crunches indicate ~350. Note that the USDA choline database only includes 630 foods, so one's real intake is certainly higher than what nutrition software indicates -- but don't let this make you overconfident of adequacy. Elevated serum creatine phosphokinase (CPK), aspartate aminotransferase (AST), alanine aminotransferase (ALT), or lactate dehydrogenase (LD) may in some cases indicate choline deficiency, tho' (a) they can be elevated for unrelated reasons, and (b) I'm not clear on how severe one's deficiency has to be before noticeable elevations will occur.

Pyroglutamic acid: VRP, my previous source, has discontinued pyroglutamic acid. I'm very annoyed: this is the SECOND time they've disc. something I use for which they're the only trustworthy source I know, and w/o notice ... And in fact, a quick Google suggests no other source (S*urce N@turals sucks (a couple of flunked consumerlabs.com tests, totally inappropriate tableting of R-LA, other bad behavior), and I don't want arginine pyroglutamate). Damn damn damn! Does anyone know of a reliable source for this supplement?? Or is anyone willing to sell me any sealed, non-expired bottles of VRP's? PM me if so, please).

CoQ10: The evidence on what CR does to CoQ levels in rodents is mixed and hard to interpret, but it's reasonable to think that a CR person's levels might be lower, due to natural downregulation of HmGCoA reductase (the enzyme opposed by statins: statin users have low CoQ, as the products of this enzyme are used to synthesize both cholesterol and CoQ). Whether elevating my serum levels with a pill do me any good is a good question, as is whether any decrease in CoQ might be part of the mechanism of CR ...

Lithium orotate: I just do my best to spread the contents of a 5 mg cap evenly over 5 days. No, this is not the pharmacological dose shown to be neuroprotective in rodents subjected to horrible pharmacological or genetic assault, nor in human disease victims, neither of which are reasonable justification for use (let alone for dosages) in normal, healthy humans. See instead (24), which presents animal studies and a surprisingly large am't of (unfortunately, but of necessity, 'ecological' rather than truly prospective) epidemiology suggesting that Li is an essential nutrient, with an 'RDA' of ~ 1 mg, whose presence in the water is linked to having a much happier (less violent, criminal, suicidal, and generally "crazy") population; see also (25), quite recently, in Japan. More recently, this same Japanese study seems to have documented a non-sneezable increase in life expectancy in the higher-Li-water communities.(32) The source I used to use (guess who :~ ?) has unfortunately quit the market, and most of the alternatives are fly-by-night operations; I would probably recommend VRP. Whatever the merits of the orotate salt specifically (and I'm skeptical, esp at this dose), there's a good chance that even these guys don't have real Li orotate: most of the material out there is just the chloride or carbonate in a blend with orotic acid in the suitable proportions; unfortunately, there's no positive test for the compound per se, and so you have to do a series of negative tests to exclude chloride and carbonate, and almost no one does this. In my former career I went looking for the real deal, and couldn't find it ANY materials suppliers that had it, despite their claims, and it had to be contract manufactured by a company that specializes in true chelates (and then, they dropped it).

Zinc: my regular diet includes what should be quite adequate zinc, but my dietary copper intake is so high I get (copper-induced secondary zinc deficiency if I don't supplement (click on the "Research" tab; most people are more likely to have the converse problem). This was mildly symptomatic for much of the year for several years (Beau's lines (more usually associated with iron deficiency), cracking fingertip skin, inability to taste zinc sulphate heptahydrate solution) when I don't, despite a fairly high dietary Zn, presumably due to high dietary copper), and even the 7 mg/d in the Veg Booster wan't quite enough to keep it at bay.

Vitamin D3: A recent meta-analysis of prospective studies posted by Sillewater(17) provides the best evidence on optimal serum levels:

We used nonparametric ("highest compared with lowest" categories) and parametric (>2 categories) statistical models to evaluate associations of 25-hydroxyvitamin D [25(OH)D] serum concentrations and mortality in observational studies among general populations ... [in data pooled from] studies that contained data on relative risks (RRs) for mortality for different 25(OH)D concentrations, which included a corresponding measure of uncertainty, and this yielded 14 prospective cohort studies that involved 5562 deaths out of 62,548 individuals. We applied log-transformed RRs and CIs, adjusted for the maximal number of confounding variables. ...

In the parametric model, the estimated summary RRs (95% CI) of mortality were 0.86 (0.82, 0.91), 0.77 (0.70, 0.84), and 0.69 (0.60, 0.78) for individuals with an increase of 12.5, 25, and 50 nmol 25(OH)D serum values/L, respectively, from a median reference category of ∼27.5 nmol/L. [MR: ie, the risk of mortality relative to an absolute serum value of ∼27.5 nmol/L (11 ng/mL) was .86 for individuals with a serum value of 40 nmol/L (16 ng/mL) 0.77 for individuals with a serum value of 52.5 nmol/L (21 ng/mL), and 0.69 for individuals with a serum value of 77.5 nmol/L (31 ng/mL)].

There was, however, no significant decrease in mortality when an increase of ∼87.5 nmol/L above the reference category occurred [ie, the mortality risk for an absolute value of 115 nmol/L (46 ng/mL) is not significantly different from having a frankly deficient serum value of ∼27.5 nmol/L (11 ng/mL): you're better off at or around 31 ng/mL].

Conclusion: Data suggest a nonlinear decrease in mortality risk as circulating 25(OH)D increases, with optimal concentrations ∼75-87.5 nmol/L [30-46 ng/mL]."(17)


You can see this in their Figure, which is nominally U-shaped, with the sweet spot at ~31 ng/mL, although the CIs don't rule out the possibility that mortality merely FLATTENS at 31 ng/mL and above, rather than reaching a true trough there with risks getting worse at higher values:

Caption: "Summary nonlinear dose-response relation (dotted lines: 95% CI) from the best-fitting random-effects model, between an increase in the concentration of 25(OH)D (ng/mL) with respect to reference values and overall mortality RR. ... Summary RR = exp (20.0850x + 0.00175x2). The lower x axis indicates the absolute 25(OH)D values. Note that 27.5 nmol/L is the median value of the reference categories of our included studies. To convert the values of 25(OH)D to ng/L, divide by 2.496. 25(OH)D, 25-hydroxyvitamin D."

At 1000-1200 IU/d, I have consistently had a little over 40 ng/dL serum 25(OH)D3. Thus, I've cut back to beneath the low end of that range, and will reasess even that dose if my levels don't drop.

Taurine: Absent in vegetarian diet; significant, altho' not ideal, data that it reduces the risk of CVD and other mortality.(33) NB that the EPA/DHA and taurine content of fish and seafood are major confounders to drawing inferences about observed benefits of fish consumption in epidemiological studies; while there are controlled trials showing lower risk of a second heart attack or major cardiovascular events with EPA/DHA supplements or extra ALA, there is as yet no real equivalent with taurine. In in Japan, the average intake appears to be 225 mg/d in males and 162 in females, with the highest intakes >1000 mg.(34)

Glycine: mostly for soundness of sleep (16). I've switched over to their AjiPure Glycine Powder, for reasons discussed in the discussion of lysine, above.

Strontium: As noted, I have low BMD typical of natural- and CR-induced low BMI; strontium is one of the best-documented supplements on the planet, having been shown in multiple clinical trials (of post- or peripausal women, NB, whose bone loss is for very different reasons and is associated with decay of bone architecture) to actively increase bone formation, raise or maintain BMD, and reduce fracture risk.

Melatonin: for sleep when stressed, wide awake, or jetlagged. 300 mcg is sufficient to raise levels to normal physiological youthful ones and apparently works as well as higher doses ((22,23), and see (21)) and doesn't produce the 'hangover' sleepiness sometimes seen with the supraphysiological 3 mg (and up) doses that became ubiquitous thanks to the recommendation of the once-notorious Melatonin Miracle.

And with that melatonin discussion, I symbolically put this thing to bed -- for another long sleep!

-Michael

Representative 2-week CRON-O-Meter:

General
===========================================
Energy | 1731.4 kcal 271%
Protein | 79.3 g 165%
Carbs | 188.2 g 63%
Fiber | 67.3 g 224%
Starch | 2.2 g
Sugars | 59.1 g
Fat | 84.0 g 382%
Alcohol | 9.3 g
Caffeine | 2.8 mg
Water | 1879.8 g 125%
Ash | 21.1 g

Vitamins (86%)
===========================================
Vitamin A | 31538.5 IU 1051%
Retinol | 105.2 µg
Alpha-carotene | 1444.6 µg
Beta-carotene | 17592.6 µg
Beta-cryptoxanthin | 23.5 µg
Lycopene | 12416.8 µg
Lutein+Zeaxanthin | 25686.3 µg
Folate | 1164.0 µg 233%
B1 (Thiamine) | 2.7 mg 227%
B2 (Riboflavin) | 2.5 mg 195%
B3 (Niacin) | 26.5 mg 166%
B5 (Pantothenic Acid)| 12.0 mg 240%
B6 (Pyridoxine) | 3.8 mg 224%
B12 (Cyanocobalamin) | 1.3 µg 55%
Vitamin C | 558.1 mg 620%
Vitamin D | 65.4 IU 16%
Vitamin E | 27.2 mg 181%
Beta Tocopherol | 0.2 mg
Delta Tocopherol | 0.0 mg
Gamma Tocopherol | 5.8 mg
Vitamin K | 1256.1 µg 1047%
Biotin | 0.0 µg 0%
Choline | 248.4 mg 45%

Minerals (100%)
===========================================
Calcium | 1214.6 mg 121%
Chromium | 0.0 µg 0%
Copper | 3.4 mg 377%
Fluoride | 92.6 µg
Iron | 21.8 mg 273%
Magnesium | 659.5 mg 157%
Manganese | 11.0 mg 480%
Phosphorus | 1700.8 mg 243%
Potassium | 6508.3 mg 138%
Selenium | 66.9 µg 122%
Sodium | 1235.1 mg 95%
Zinc | 14.5 mg 132%

Amino Acids (93%)
===========================================
ALA | 3.2 g
ARG | 4.9 g
ASP | 6.8 g
CYS | 1.0 g 70%
GLU | 11.5 g
GLY | 2.6 g
HIS | 1.6 g 151%
HYP | 0.0 g
ILE | 2.8 g 194%
LEU | 4.5 g 140%
LYS | 3.7 g 125%
MET | 1.1 g 74%
PHE | 3.0 g 117%
PRO | 3.1 g
SER | 3.1 g
THR | 2.5 g 165%
TRP | 0.8 g 220%
TYR | 2.1 g 85%
VAL | 3.4 g 1116%

Lipids (55%)
===========================================
Saturated | 9.9 g
Monounsaturated | 50.8 g
Polyunsaturated | 17.3 g
Omega-3 | 4.8 g 121%
Omega-6 | 12.5 g
Trans-Fats | 0.0 g
Cholesterol | 27.0 mg 9%
Phytosterol | 199.5 mg

References
3. Soffritti M, Belpoggi F, Degli Esposti D, Lambertini L, Tibaldi E, Rigano A. First experimental demonstration of the multipotential carcinogenic effects of aspartame administered in the feed to Sprague-Dawley rats. Environ Health Perspect. 2006 Mar;114(3):379-85. PMID: 16507461 [PubMed - indexed for MEDLINE]

4. Gallus S, Scotti L, Negri E, Talamini R, Franceschi S, Montella M, Giacosa A, Dal Maso L, La Vecchia C. Artificial sweeteners and cancer risk in a network of case-control studies. Ann Oncol. 2007 Jan;18(1):40-4. Epub 2006 Oct 16. PMID: 17043096 [PubMed - indexed for MEDLINE]

5. Lim U, Subar AF, Mouw T, Hartge P, Morton LM, Stolzenberg-Solomon R, Campbell D, Hollenbeck AR, Schatzkin A. Consumption of aspartame-containing beverages and incidence of hematopoietic and brain malignancies. Cancer Epidemiol Biomarkers Prev. 2006 Sep;15(9):1654-9. PMID: 16985027 [PubMed - indexed for MEDLINE]

5a. Humphries P, Pretorius E, Naudé H. Abstract Direct and indirect cellular effects of aspartame on the brain. Eur J Clin Nutr. 2008 Apr;62(4):451-62. Epub 2007 Aug 8. PMID: 17684524 [PubMed - in process] http://www.nature.co...866a.pdf

6: Geogescu A, Popov D. Age-dependent accumulation of advanced glycatin endproducts is accelerated in combined hyperlipidemia and hyperglycemia, a process attenuated by L-arginine. J Amer Aging Assoc. 2000 Jan;23(1):23-30.

6a. Lubec B, Golej J, Marx M, Weninger M, Hoeger H. L-arginine reduces kidney lipid peroxidation, glycoxidation and collagen accumulation in the aging NMRI mouse. Ren Physiol Biochem. 1995 Mar-Apr;18(2):97-102. PMID: 7539539 [PubMed - indexed for MEDLINE]

7. Weninger M, Xi Z, Lubec B, Szalay S, Hoger H, Lubec G. L-arginine reduces glomerular basement membrane collagen N epsilon-carboxymethyllysine in the diabetic db/db mouse. Nephron. 1992;62(1):80-3. PMID: 1436297

8. Radner W, Hoger H, Lubec B, Salzer H, Lubec G. L-arginine reduces kidney collagen accumulation and N-epsilon-(carboxymethyl)lysine in the aging NMRI-mouse. J Gerontol. 1994 Mar;49(2):M44-6. PMID: 8126351 [PubMed - indexed for MEDLINE]

9. Sensi M, De Rossi MG, Celi FS, Cristina A, Rosati C, Perrett D, Andreani D, Di Mario U. D-lysine reduces the non-enzymatic glycation of proteins in experimental diabetes mellitus in rats. Diabetologia. 1993 Sep;36(9):797-801. PMID: 8405749 [PubMed - indexed for MEDLINE]

10. Khaidar A, Marx M, Lubec B, Lubec G. L-arginine reduces heart collagen accumulation in the diabetic db/db mouse. Circulation. 1994 Jul;90(1):479-83. PMID: 8026034 [PubMed - indexed for MEDLINE]

11. Lubec G, Vierhapper H, Bailey AJ, Damjancic P, Fasching P,Sims TJ, Kampel1 D, Popow C, Bartosch B. Influence of L-arginine on glucose mediated collagen cross link precursors in patients with diabetes mellitus. Amino Acids. 1991 Feb;1(1):73 – 80.

12. Jyothirmayi GN, Modak R, Reddi AS. L-lysine reduces nonenzymatic glycation of glomerular basement membrane collagen and albuminuria in diabetic rats. Nephron. 2001 Feb;87(2):148-54. PMID: 11244310 [PubMed - indexed for MEDLINE]

12a: Sulochana KN, Punitham R, Ramakrishnan S. Beneficial effect of lysine and amino acids on cataractogenesis in experimental diabetes through possible antiglycation of lens proteins. Exp Eye Res. 1998 Nov;67(5):597-601. PubMed PMID: 9878222.

13. Contreras I, Reiser KM, Martinez N, Giansante E, Lopez T, Suarez N, Postalian S, Molina M, Gonzalez F, Sanchez MR, Camejo M, Blanco MC. Effects of aspirin or basic amino acids on collagen cross-links and complications in NIDDM. Diabetes Care. 1997 May;20(5):832-5. PMID: 9135951

16: Inagawa K, Hiraoka T, Kohda T, Yamadera W, Takahashi M. Subjective effects of glycine ingestion before bedtime on sleep quality. Sleep and Biological Rhythms.2006 Fe;4(1):75-7.

17. Zittermann A, Iodice S, Pilz S, Grant WB, Bagnardi V, Gandini S. Vitamin D deficiency and mortality risk in the general population: a meta-analysis of prospective cohort studies. Am J Clin Nutr. 2011 Dec 14. [Epub ahead of print] PubMed PMID: 22170374.

18: Rae C, Digney AL, McEwan SR, Bates TC. Oral creatine monohydrate supplementation improves brain performance: a double-blind, placebo-controlled, cross-over trial. Proc Biol Sci. 2003 Oct 22;270(1529):2147-50. PubMed PMID: 14561278; PubMed Central PMCID: PMC1691485.

19. Di Castelnuovo A, Costanzo S, Bagnardi V, Donati MB, Iacoviello L, de Gaetano G. Alcohol dosing and total mortality in men and women: an updated meta-analysisof 34 prospective studies. Arch Intern Med. 2006 Dec 11-25;166(22):2437-45. PubMed PMID: 17159008.

20. Streppel MT, Ocké MC, Boshuizen HC, Kok FJ, Kromhout D. Long-term wine consumption is related tocardiovascular mortality and life expectancy independently of moderate alcohol intake: the Zutphen Study. J Epidemiol Community Health. 2009 Jul;63(7):534-40. PubMed PMID: 19406740.

21: Brzezinski A, Vangel MG, Wurtman RJ, Norrie G, Zhdanova I, Ben-Shushan A, Ford I. Effects of exogenous melatonin on sleep: a meta-analysis. Sleep Med Rev. 2005 Feb;9(1):41-50. PubMed PMID: 15649737.

22: Zhdanova IV, Wurtman RJ, Morabito C, Piotrovska VR, Lynch HJ. Effects of low oral doses of melatonin, given 2-4 hours before habitual bedtime, on sleep in normal young humans. Sleep. 1996 Jun;19(5):423-31. PubMed PMID: 8843534.

23: Zhdanova IV, Wurtman RJ, Lynch HJ, Ives JR, Dollins AB, Morabito C, Matheson JK, Schomer DL. Sleep-inducing effects of low doses of melatonin ingested in the evening. Clin Pharmacol Ther. 1995 May;57(5):552-8. PubMed PMID: 7768078.

24. Schrauzer GN. Lithium: occurrence, dietary intakes, nutritional essentiality. J Am Coll Nutr. 2002 Feb ;21 (1):14-21. PMID 11838882

25. Ohgami H, Terao T, Shiotsuki I, Ishii N, Iwata N. Lithium levels in drinking water and risk of suicide. Br J Psychiatry. 2009 May ;194 (5):464-5; discussion 446. PMID 19407280

32. Zarse K, Terao T, Tian J, Iwata N, Ishii N, Ristow M. Low-dose lithium uptake promotes longevity in humans and metazoans. Eur J Nutr. 2011 Feb 8. [Epub ahead of print] PubMed PMID: 21301855.

32: Yamori Y, Liu L, Mori M, Sagara M, Murakami S, Nara Y, Mizushima S. Taurine as
the nutritional factor for the longevity of the Japanese revealed by a world-wide
epidemiological survey. Adv Exp Med Biol. 2009;643:13-25. PubMed PMID: 19239132.

33: Laura Della Corte (Editor), Ryan J. Huxtable (Editor), Giampietro Sgaragli (Editor), Keith F. Tipton (Editor). Taurine 4: Taurine and Excitable Tissues: Taurine and Excitable Tissues No. 4 (Advances in Experimental Medicine and Biology Volume 483). ISBN (9780306464478) . See here (Fig. 3) and here (Fig. 1).

35: Villareal DT, Kotyk JJ, Armamento-Villareal RC, Kenguva V, Seaman P, Shahar A, Wald MJ, Kleerekoper M, Fontana L. Reduced bone mineral density is not associated with significantly reduced bone quality in men and women practicing long-term calorie restriction with adequate nutrition. Aging Cell. 2011 Feb;10(1):96-102. doi: 10.1111/j.1474-9726.2010.00643.x. Epub 2010 Nov 15. PubMed PMID: 20969721.

36. Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, Britt EB, Fu X, Wu Y, Li L, Smith JD, Didonato JA, Chen J, Li H, Wu GD, Lewis JD, Warrier M, Brown JM, Krauss RM, Tang WH, Bushman FD, Lusis AJ, Hazen SL. Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013 May;19(5):576-85. doi: 10.1038/nm.3145. Epub 2013 Apr 7. PubMed PMID: 23563705; PubMed Central PMCID: PMC3650111.

37. Pepino MY, Tiemann CD, Patterson BW, Wice BM, Klein S. Sucralose Affects Glycemic and Hormonal Responses to an Oral Glucose Load. Diabetes Care. 2013 Apr 30. [Epub ahead of print] PubMed PMID: 23633524.

38. Costanzo S, Di Castelnuovo A, Donati MB, Iacoviello L, de Gaetano G. Wine, beer or spirit drinking in relation to fatal and non-fatal cardiovascular events: a meta-analysis. Eur J Epidemiol. 2011 Nov;26(11):833-50. doi: 10.1007/s10654-011-9631-0. Epub 2011 Nov 11. PubMed PMID: 22076059.


Edited by Michael, 15 June 2013 - 06:22 PM.

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#2 nowayout

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Posted 10 February 2012 - 08:18 PM

Regarding L-arginine, do you think the following suggests caution? Sure, it is in an arterial disease state, but the fact that patients on L-arginine did worse than placebo in that model suggests that it is not just frank tolerance but rather vascular harm happening and makes me wary of chronic L-arginine use also in healthy people.

http://circ.ahajourn...116/2/188.short

l-Arginine Supplementation in Peripheral Arterial Disease

No Benefit and Possible Harm

Background— l-Arginine is the precursor of endothelium-derived nitric oxide, an endogenous vasodilator. l-Arginine supplementation improves vascular reactivity and functional capacity in peripheral arterial disease (PAD) in small, short-term studies. We aimed to determine the effects of long-term administration of l-arginine on vascular reactivity and functional capacity in patients with PAD.
Methods and Results— The Nitric Oxide in Peripheral Arterial Insufficiency (NO-PAIN) study was a randomized clinical trial of oral l-arginine (3 g/d) versus placebo for 6 months in 133 subjects with intermittent claudication due to PAD in a single-center setting. The primary end point was the change at 6 months in the absolute claudication distance as assessed by the Skinner-Gardner treadmill protocol. l-Arginine supplementation significantly increased plasma l-arginine levels. However, measures of nitric oxide availability (including flow-mediated vasodilation, vascular compliance, plasma and urinary nitrogen oxides, and plasma citrulline formation) were reduced or not improved compared with placebo. Although absolute claudication distance improved in both l-arginine- and placebo-treated patients, the improvement in the l-arginine-treated group was significantly less than that in the placebo group (28.3% versus 11.5%; P=0.024).
Conclusions— In patients with PAD, long-term administration of l-arginine does not increase nitric oxide synthesis or improve vascular reactivity. Furthermore, the expected placebo effect observed in studies of functional capacity was attenuated in the l-arginine-treated group. As opposed to its short-term administration, long-term administration of l-arginine is not useful in patients with intermittent claudication and PAD.


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#3 albedo

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Posted 11 February 2012 - 02:03 PM

Thank you, very interesting and much need update.

Edited by albedo, 11 February 2012 - 02:06 PM.

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#4 nowayout

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Posted 11 February 2012 - 04:32 PM

Ethanol itself is what appears to be responsible for a good part of the decreased mortality effect (in moderation), so by taking a red wine extract you might well be losing most of the benefit. I prefer my intake to be in the form of red wine because I like it, but am not sold on the red wine hypothesis. The supposed additional effect from red wine was not reproduced in some studies, and if real, may well be mostly from socioeconomic factors associated with red wine consumption.

Edited by viveutvivas, 11 February 2012 - 04:35 PM.

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#5 Michael

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Posted 11 February 2012 - 05:27 PM

Ethanol itself is what appears to be responsible for a good part of the decreased mortality effect (in moderation), so by taking a red wine extract you might well be losing most of the benefit. ... The supposed additional effect from red wine was not reproduced in some studies, and if real, may well be mostly from socioeconomic factors associated with red wine consumption.

First, to be clear, I don't eschew alcohol: see my diet. I consume 1x3oz serving of wine a day, with a meal, which is consistent with the best mortality outcome in studies looking specifically at wine, and in the ballpark even for total alcohol. I actually regard red wine as one of the best-supported "health foods" out there, and would think it foolish to avoid alcohol in favor of a speculation about red wine polyphenols (unless one has, or has reason to think one might be vulnerable to, a problem with alcohol).

However, there does seem to be something to the non-alcohol constituents of wine. Studies on other forms of alcohol, or total alcohol consumption, show a reduction in cardiovascular mortality, but not total mortality -- and the evidence that wine (and not other alcoholic beverages) protects against dementia is substantial, while other or total alchol consumption seems overall nonprotective or deleterious. So there's (likely) "something else in wine" accounting for the difference, and that sure seems likely to be the polyphenols. I agree that SES confounders are significant, and some studies have indeed found that they erase the difference -- but most don't, including what I would consider to be the best such studies. And I would certainly say that supplementation reflecting the levels and species of polyphenols actually present in a couple of glasses of wine (as vs. supplements that say "red wine" but are actually made from unfermented grape components, or as vs. megadoses of resveratrol or other constituents in isolation) presents a very low risk, and a significant potential reward.

Regarding L-arginine, do you think the following suggests caution? Sure, it is in an arterial disease state, but the fact that patients on L-arginine did worse than placebo in that model suggests that it is not just frank tolerance but rather vascular harm happening and makes me wary of chronic L-arginine use also in healthy people.

Good point. Tho' I'd seen this trial, I hadn't really thought about how relatively little they had used (vs. this one that used 9 g). As you say, these were sick people, and there's reason to think that the higher oxidative stress in such folk, and maybe folate deficiency, would be harmful in a way that it wouldn't be for the rest of us;(1-4) and, my dose is only 500 mg half the time and 2 g total the other half, tho' I see worryingly that in the Wilson et al PAD trial, "patients were randomly assigned to either l-arginine (1 g TID with meals) or placebo," so my single bolus is occasionaly higher, and unopposed.

(In case any readers don't know it: you shold avoid arginine supplements IAC if you have oral or genital herpes; an all-lysine approach would apparently have the added merit to actively reducing the severity of your outbreaks).

I will ponder this further; thanks!

References
1: Tsai CH, Pan TL, Lee YS, Tai YK, Liu TZ. Evidence that high-dose L-arginine may be inappropriate for use by diabetic patients as a prophylactic blocker of methylglyoxal glycation. J Biomed Sci. 2004 Sep-Oct;11(5):692-6. PubMed PMID: 15316145.

2: Loscalzo J. Homocysteine trials--clear outcomes for complex reasons. N Engl J Med. 2006 Apr 13;354(15):1629-32. Epub 2006 Mar 12. PubMed PMID: 16531615.

3: Jahangir E, Vita JA, Handy D, Holbrook M, Palmisano J, Beal R, Loscalzo J, Eberhardt RT. The effect of L-arginine and creatine on vascular function and homocysteine metabolism. Vasc Med. 2009 Aug;14(3):239-48. PubMed PMID: 19651674; PubMed Central PMCID: PMC2840406.

4: Cosentino F, Hürlimann D, Delli Gatti C, Chenevard R, Blau N, Alp NJ, Channon KM, Eto M, Lerch P, Enseleit F, Ruschitzka F, Volpe M, Lüscher TF, Noll G. Chronic treatment with tetrahydrobiopterin reverses endothelial dysfunction and oxidative stress in hypercholesterolaemia. Heart. 2008 Apr;94(4):487-92. Epub 2007 Oct 4. PubMed PMID: 17916662.
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#6 nameless

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Posted 11 February 2012 - 09:25 PM

Thanks for the update. I find the Vitamin D info useful.

As far as a red wine extract goes, have you ever looked into Polyphenolics red wine extract?


MegaNatural® RED WINE Concentrate

MegaNatural® RED WINE Concentrate is produced from 100% California red wines. It is standardized at > 25% polyphenols and >8% anthocyanins and produced as a powder. This is not just a spray dried wine but a special wine high in anthocyanins that is controlled to minimize malolactic formation. The red wine is fermented, lactic acid controlled and alcohol is removed. A limited extraction is performed removing some sugars and proteins. The product is in powder form and comes in 10 kg containers (Item #: GW3050).


http://www.meganatur...olics-products/


No idea if it's any good, or who even sells it as a finished product though. If expensive as a raw product, it could be similar to Provinols... nice, but impossible to find.
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#7 albedo

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Posted 11 February 2012 - 09:50 PM

....
11:10 AM, with green tea:
0.5 g Beta-alanine
Brain nutrient (rotating one of: 800 mg piracetam ( why?) (once/wk), pyroglutamate (500 mg, thrice/wk) and ALCAR (250 mg thrice/wk)
....

Which is your source of ALCAR?
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#8 Sillewater

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Posted 14 February 2012 - 02:43 AM

Thanks MR for your updated regimen. With regards to glycine I was wondering if you had a comment on this study I posted here: http://www.longecity...545#entry498545

Cell. 2012 Jan 20;148(1-2):259-72. Epub 2012 Jan 5.Glycine decarboxylase activity drives non-small cell lung cancer tumor-initiating cells and tumorigenesis.Zhang WC, Shyh-Chang N, Yang H, Rai A, Umashankar S, Ma S, Soh BS, Sun LL, Tai BC, Nga ME, Bhakoo KK, Jayapal SR, Nichane M, Yu Q, Ahmed DA, Tan C, Sing WP, Tam J, Thirugananam A, Noghabi MS, Huei Pang Y, Ang HS, Robson P, Kaldis P, Soo RA, Swarup S, Lim EH, Lim B.


I'm still doing research when I have time but I would guess that if glycine at 5g has an inhibitory effect (on sleep) then levels may be high enough to induce GD.
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#9 sdxl

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Posted 14 February 2012 - 03:38 AM

Creatine: As noted, I'm vegetarian, and our levels are lower than omnivores' and trials seem to show that vegetarians' brains work better on some tasks when given a low-dose supplement(18). If you use creatine, insist on a supplement made using CreaPure (a branded raw material manufactured by Degussa AG Trostberg (formerly SKW) but used in several different retail brands).

Since you are updating your regimen, you might want to update that Creapure is manufactured by AlzChem AG.
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#10 Cephalon

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Posted 16 February 2012 - 07:05 PM

Hi Michael, thanks for the update, I was going to ask you for an 2012 update anyway!

If I remember correctly you were using 5g Creapure creatine in your previous regime. Any specific reason for reducing your intake?
I use just 2g a day, because more gives me GI discomfort. I'm a vegetarian as well.

I see you cut back on B12 prety much, could you expalin why?

Regarding the Phosphatidylcholine:
So in the end you are getting 55mg free choline, but isn't the suggested dietary intake of free choline approx. 550mg?
I have the same problem with Choline and my vegetarian/ more or less vegan diet. I found out CDP-Choline made me nervous when taken everyday, and I feel Choline Bitartrate 's ill systemic effects.
I understand Phosphatidylcholine is the favourable form of Choline, since it comes this way in the products I avoid (eggs ...).
I'm just under the impression that we'd need to take 10times your current amount of Phosphatidylcholine to meet the suggested 550mg, wouldn't we?

Edited by Michael, 18 February 2012 - 12:44 AM.

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#11 nowayout

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Posted 18 February 2012 - 02:24 AM

I see you are taking co-Q10 again.

But in 2004 you said:

Stop taking CoQ10 - some evidence of "crap" in hearts, livers and kidney in mice in CoQ10 group. May be why there was a hint of *decreased* lifespan from CoQ10 in mice.


What made you change your mind?
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#12 Michael

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Posted 18 February 2012 - 05:25 PM

As far as a red wine extract goes, have you ever looked into [ MegaNatural® RED WINE Concentrate]?

No -- I'd never heard of it! And this is a side business for Constellation Wines, who are a huge mass-market N American wine producer, so it should be authentic. Thank you very much. Sadly, I can't find any decent products (they have decent-looking success with MegaNatural-BP, which is just grape seed extract); I've emailed them to ask, but it's been several days without response so I may bug them by phone.

Thanks MR for your updated regimen. With regards to glycine I was wondering if you had a comment on this study [(0) below] I posted here: http://www.longecity...545#entry498545

I'm still doing research when I have time but I would guess that if glycine at 5g has an inhibitory effect (on sleep) then levels may be high enough to induce GD.

My comments are (a) don't base your decisions on spinning mechanistic hypotheses from in vitro studies, and (b) do use PubMed to look for in vivo studies, which show either no effect or an anticancer effect (via inhibition of excessive but apparently not normal angiogenesis, and inhibiting Kupffer cell activity in the liver) of high dietary glycine supplementation. (1-7) This was not a hard search ...

If I remember correctly you were using 5g Creapure creatine in your previous regime. Any specific reason for reducing your intake?

First, because this is more than enough to correct for my low intake as a vegetarian; second, because the trial I cited ((18) in original post) used about this much; and third: see teh safety post I linked in my discussion.

I see you cut back on B12 prety much, could you expalin why?

I did, in the followup to posting my earlier intake. (Thanks, Funk, if you're ever reading this ...).

Regarding the Phosphatidylcholine:
So in the end you are getting 55mg free choline, but isn't the suggested dietary intake of free choline approx. 550mg?

Please re-read my original post ... count pills, and also remember that I do actually eat food. ;)

I see you are taking co-Q10 again. But in 2004 you said:

Stop taking CoQ10 - some evidence of "crap" in hearts, livers and kidney in mice in CoQ10 group. May be why there was a hint of *decreased* lifespan from CoQ10 in mice.

What made you change your mind?

See my note on CoQ in my originating post. Note also that in the studies in which LS was unchanged or possibly decreased (several studies, including (8)), and in which supplemented animals suffered "deposition of a crystalline-appearing, insoluble material in areas of the heart, liver, and kidney" (8) -- in these studies, the doses used was a great deal higher than what I'm taking, no matter how you scale the dose. My comments in '04 were intended to counsel against the use of the much higher doses used and promoted for use in healthy people (based on weak results in trials for blood pressure and more convicing studies in heart failure) as a supposed life extension agent, despite the fact that it very clearly does not extend life.

References
0. Cell. 2012 Jan 20;148(1-2):259-72. Epub 2012 Jan 5.Glycine decarboxylase activity drives non-small cell lung cancer tumor-initiating cells and tumorigenesis.Zhang WC, Shyh-Chang N, Yang H, Rai A, Umashankar S, Ma S, Soh BS, Sun LL, Tai BC, Nga ME, Bhakoo KK, Jayapal SR, Nichane M, Yu Q, Ahmed DA, Tan C, Sing WP, Tam J, Thirugananam A, Noghabi MS, Huei Pang Y, Ang HS, Robson P, Kaldis P, Soo RA, Swarup S, Lim EH, Lim B.

1: Laschke MW, Schwender C, Scheuer C, Vollmar B, Menger MD. Dietary glycine does not affect physiological angiogenesis and reproductive function, but inhibits apoptosis in endometrial and ovarian tissue by down-regulation of nuclear factor-kappaB. Fertil Steril. 2008 Oct;90(4 Suppl):1460-9. Epub 2007 Dec 11. PubMed PMID: 18054919.

2: Yamashina S, Ikejima K, Rusyn I, Sato N. Glycine as a potent anti-angiogenic nutrient for tumor growth. J Gastroenterol Hepatol. 2007 Jun;22 Suppl 1:S62-4. Erratum in: J Gastroenterol Hepatol. 2008 Mar;23(3):501-2. PubMed PMID: 17567469.

3: Bunaciu RP, Tharappel JC, Lehmler HJ, Kania-Korwel I, Robertson LW, Srinivasan C, Spear BT, Glauert HP. The effect of dietary glycine on the hepatic tumor promoting activity of polychlorinated biphenyls (PCBs) in rats. Toxicology. 2007 Oct 8;239(3):147-55. Epub 2007 Jul 7. PubMed PMID: 17703865; PubMed Central PMCID: PMC2063585.

4: Amin K, Li J, Chao WR, Dewhirst MW, Haroon ZA. Dietary glycine inhibits angiogenesis during wound healing and tumor growth. Cancer Biol Ther. 2003 Mar-Apr;2(2):173-8. PubMed PMID: 12750558.

5: Rose ML, Cattley RC, Dunn C, Wong V, Li X, Thurman RG. Dietary glycine prevents the development of liver tumors caused by the peroxisome proliferator WY-14,643. Carcinogenesis. 1999 Nov;20(11):2075-81. PubMed PMID: 10545408.

6: Rose ML, Madren J, Bunzendahl H, Thurman RG. Dietary glycine inhibits the growth of B16 melanoma tumors in mice. Carcinogenesis. 1999 May;20(5):793-8. PubMed PMID: 10334195.

7: Vasudevan S, Laconi E, Abanobi SE, Rao PM, Rajalakshmi S, Sarma DS. Effect of glycine on the induction of orotic aciduria and urinary bladder tumorigenesis in the rat. Toxicol Pathol. 1987;15(2):194-7. PubMed PMID: 3616403.

8: Lee CK, Pugh TD, Klopp RG, Edwards J, Allison DB, Weindruch R, Prolla TA. The impact of alpha-lipoic acid, coenzyme Q10 and caloric restriction on life span and gene expression patterns in mice. Free Radic Biol Med. 2004 Apr 15;36(8):1043-57. PubMed PMID: 15059645. Lifespan results on CoQ and lipoic acid.

Edited by Michael, 28 June 2012 - 12:35 PM.

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#13 Cephalon

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Posted 18 February 2012 - 07:43 PM

Thanks Michael, I accidentally skipped your second Phosphatidylcholine dose :)
I'm sure you get enough choline this way.
Lecithine has to many KCals right?
It's so much cheaper ... the Phosphatidylcholine w'd cost me a fortune to get in Gerrmany.
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#14 Michael

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Posted 18 February 2012 - 08:01 PM

Thanks Michael, I accidentally skipped your second Phosphatidylcholine dose :)

... and are still skipping the third, apparently ;) . And it doesn't sound as if you've yet looked at my diet ...

Lecithine has to many KCals right?

... and oxidizable linoleic acid, and opportunity for bacterial degradation of its PC to TMA(O), and just junk that I don't want.

It's so much cheaper ... the Phosphatidylcholine w'd cost me a fortune to get in Gerrmany.

Pardon my ignorance, but is that really true, with harmonization in the EU? It's certainly quite inexpensive in the UK, tho' not as cheap as in USA or CAN ...
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#15 Cephalon

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Posted 18 February 2012 - 08:19 PM

:) Sorry, has been a tough day ... Ok finaly I found the last one you were hiding there.
I did check your diet, but there was just this small difference, which your third dose certainly makes up. Sorry ..

Yes, of course UK Supplement prices are alot lower than German ones, still higher than US or Canadian prices. I buy 90% of my supps in the UK, especially because of the harmonization. German customs stop and return all non EU supplement orders recently.
I will check the UK suppliers for it, thanks!
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#16 nameless

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Posted 20 February 2012 - 08:07 PM

Lecithine has to many KCals right?

... and oxidizable linoleic acid, and opportunity for bacterial degradation of its PC to TMA(O), and just junk that I don't want.

This may fall under the category of a 'dumb question', but what is your view on lecithin used in encapsulated supplements? Namely, when used as an emulsifier w/ CoQ10/Ubiquinol?

Would it oxidize or degrade while being encapsulated or perhaps the amount is too small to matter anyway, seeing as it's used as an emulsifier only?
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#17 Michael

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Posted 20 February 2012 - 08:27 PM

Lecithine has to many KCals right?

... and oxidizable linoleic acid, and opportunity for bacterial degradation of its PC to TMA(O), and just junk that I don't want.

This may fall under the category of a 'dumb question', but what is your view on lecithin used in encapsulated supplements? Namely, when used as an emulsifier w/ CoQ10/Ubiquinol?

Would it oxidize or degrade while being encapsulated or perhaps the amount is too small to matter anyway, seeing as it's used as an emulsifier only?

I think, as you suggest, that the small quantity used as an emulsifier makes the likely levels of peroxides or TMA(O) trivial, if the product is at all fresh; plus, in the specific case of taking it with ubiquinol, you have an antioxidant to protect it from oxidizing, and the softgel protects it from bacteria to some extent (tho' of course it may have had some of either in it before it was encapsulated).

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 ....
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#18 Arbor

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Posted 23 February 2012 - 05:49 PM

M. Rae wrote:
"Melatonin: for sleep when stressed, wide awake, or jetlagged. 300 mcg is sufficient to raise levels to normal physiological youthful ones and apparently works as well as higher doses ((22,23), and see (21)) and doesn't produce the 'hangover' sleepiness sometimes seen with the supraphysiological 3 mg (and up) doses that became ubiquitous thanks to the recommendation of the once-notorious."

Thanks for posting an update of your supps protocol.

I am yet to find a melatonine supplement that has an affect on me. May I ask please which one you take (I couldn't find a mention in your past postings @ the links you provided in this version)?

Thanks
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#19 Donnie

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Posted 23 February 2012 - 06:01 PM

At 1000-1200 IU/d, I have consistently had a little over 40 nmol/L serum 25(OH)D3. Thus, I've cut back to beneath the low end of that range, and will reasess even that dose if my levels don't drop.


You mean ng/mL, right?
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#20 sthira

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Posted 23 February 2012 - 08:39 PM

You mention scary over consumption of iodine in sea vegetables. Laver seems lower:

http://www.seaveg.co...id=15&chapter=a

It's yummy, and eat a vegan diet. Should I stop eating this stuff? I may already know this answer since I spend time on the sea, and recognize how we humans treat the ocean as if it's a big toilet. But iodine?


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#21 Mind

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Posted 23 February 2012 - 09:32 PM

Briefly scouring your regimen, I would conclude that it is constructed for optimum health and to slow the aging process as much as possible. Is there anything in there that is specifically targeted toward rejuvenation or reversal of aging damage, within cells or a particular organ/body part?
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#22 mikeinnaples

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Posted 27 February 2012 - 01:43 PM

Unlike the shaky-to-begin-with-and-now-disproven resveratrol hype, there is a quite solid body of epidemiological evidence of an association between a couple of glasses of wine a day and lower risk of a range of adverse outcomes, including total mortality and dementia.


I know your thoughts on this as a CR mimetic hype quite clearly, and I have come to agree with you..... however, are you saying that it holds no supplemental value period?
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#23 Michael

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Posted 28 February 2012 - 05:21 PM

M. Rae wrote:

"Melatonin: for sleep when stressed, wide awake, or jetlagged. 300 mcg is sufficient to raise levels to normal physiological youthful ones and apparently works as well as higher doses ((22,23), and see (21)) and doesn't produce the 'hangover' sleepiness sometimes seen with the supraphysiological 3 mg (and up) doses that became ubiquitous thanks to the recommendation of the once-notorious."


I am yet to find a melatonine supplement that has an affect on me. May I ask please which one you take (I couldn't find a mention in your past postings @ the links you provided in this version)?


There are very few brands that even offer a dose this low; I'm currently using LEF.

At 1000-1200 IU/d, I have consistently had a little over 40 nmol/L serum 25(OH)D3. Thus, I've cut back to beneath the low end of that range, and will reasess even that dose if my levels don't drop.


You mean ng/mL, right?


Good catch -- thanks. Corrected.

You mention scary over consumption of iodine in sea vegetables. Laver seems lower:

http://www.seaveg.co...id=15&chapter=a

It's yummy, and eat a vegan diet. Should I stop eating this stuff? I may already know this answer since I spend time on the sea, and recognize how we humans treat the ocean as if it's a big toilet. But iodine?


I confess to being spooked enough by my kombu experience to be reluctant to endorse any seaweed, and at some level the ocean is "one bathtub." (1) is cited by a few sources as containing this data, but I can't find it online and they don't cite numbers. However, other sources do seem to indicate that levels are not crazy: (3) says that nori (Porphyra tenera = laver), amongst a range of seaweed samples "available from commercial sources in the United States, as well as harvester-provided samples from Canada, Tasmania, and Namibia" contained 16 microg/g (+/-2) , tho' it's not clear which of the above sources were used for this datum; (4) says that dried "purple (Porphyra sp.) lavers (nori) ...contained lesser amounts of dietary iodine (approximately 4-6 µg/100 g of dry weight) relative to other seaweeds" (the journal page confirms that it's µg, not mg as per PubMed).

Briefly scouring your regimen, I would conclude that it is constructed for optimum health and to slow the aging process as much as possible. Is there anything in there that is specifically targeted toward rejuvenation or reversal of aging damage, within cells or a particular organ/body part?


I'm not aware of any evidence that any supplement even slows down the aging process, let alone rejuvenates the body in whole or in part. Oh, wait: I do have a Secret Rejuvenation Forumula, which I am now offering to send to anyone in exchange for a pre-order, made in the form of setting up a montly subscription plan. Pills will ship once we get a critical mass in pre-orders, sufficient for me to arrange for the pills to be manufactured. They're time-release pills, so it will take a little while thereafter for the rejuvenation pills to activate.*

Unlike the shaky-to-begin-with-and-now-disproven resveratrol hype, there is a quite solid body of epidemiological evidence of an association between a couple of glasses of wine a day and lower risk of a range of adverse outcomes, including total mortality and dementia.


I know your thoughts on this as a CR mimetic hype quite clearly, and I have come to agree with you..... however, are you saying that it holds no supplemental value period?


There is some quite reasonable evidence that it might be useful to counteract some of the metabolic derangements of obesity, although the human studies are short-term. There is certainly no good evidence for a normal, healthy person to take the stuff at the moment, although I would like to see the health benefits in the 2008 nonobese mouse study (2) replicated, and some further insight gained on how the animals can be 'healthier' and still die on schedule.

*Apologies, Mind, for having a bit of fun with that ;) .

References
1. Moon SJ, Kim JY, Chung YJ, Chung YS: The iodine content in common Korean foods. Korean J Nutr. 31: 206-212, 1998.

2. Pearson KJ, Baur JA, Lewis KN, Peshkin L, Price NL, Labinskyy N, Swindell WR, Kamara D, Minor RK, Perez E, Jamieson HA, Zhang Y, Dunn SR, Sharma K, Pleshko N, Woollett LA, Csiszar A, Ikeno Y, Le Couteur D, Elliott PJ, Becker KG, Navas P, Ingram DK, Wolf NS, Ungvari Z, Sinclair DA, de Cabo R. Resveratrol Delays Age-Related Deterioration and Mimics Transcriptional Aspects of Dietary Restriction without Extending Life Span. Cell Metab. 2008 Aug;8(2):157-68. PMID: 18599363 [PubMed - as supplied by publisher]

3: Teas J, Pino S, Critchley A, Braverman LE. Variability of iodine content in common commercially available edible seaweeds. Thyroid. 2004 Oct;14(10):836-41. PubMed PMID: 15588380.

3: Watanabe F, Takenaka S, Katsura H, Masumder SA, Abe K, Tamura Y, Nakano Y. Dried green and purple lavers (Nori) contain substantial amounts of biologically active vitamin B(12) but less of dietary iodine relative to other edible seaweeds. J Agric Food Chem. 1999 Jun;47(6):2341-3. PubMed PMID: 10794633.
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#24 nowayout

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Posted 28 February 2012 - 07:13 PM

... some further insight gained on how the animals can be 'healthier' and still die on schedule.


I think the obvious conclusion is that they are not including all (or perhaps any?) of the relevant biomarkers in their analysis, when they say that "resveratrol delays age-related deterioration". If it were true that deterioration of the biomarkers actually relevant to lifespan really deteriorated more slowly, the animals wouldn't die on schedule. Either there are some gatekeeper biomarkers that are not considered by the authors, or there are biomarkers that are worsened by resveratrol, thus eliminating any advantage from the ones considered. The latter possibility is the more troubling one, in my opinion, when it comes to safety of supplementation in healthy humans.

Edited by viveutvivas, 28 February 2012 - 07:15 PM.

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#25 niner

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Posted 28 February 2012 - 09:20 PM

... some further insight gained on how the animals can be 'healthier' and still die on schedule.


I think the obvious conclusion is that they are not including all (or perhaps any?) of the relevant biomarkers in their analysis, when they say that "resveratrol delays age-related deterioration". If it were true that deterioration of the biomarkers actually relevant to lifespan really deteriorated more slowly, the animals wouldn't die on schedule. Either there are some gatekeeper biomarkers that are not considered by the authors, or there are biomarkers that are worsened by resveratrol, thus eliminating any advantage from the ones considered. The latter possibility is the more troubling one, in my opinion, when it comes to safety of supplementation in healthy humans.


I think there are some reasonable ways that an animal could be 'healthier' and still die on schedule. Mice have a habit of dying of cancer, for example, but what if there is also a late life metabolic or mitochondrial dysfunction that is helped by a supplement? The mice might then be more active, up until the point where the other normal disease state takes over.
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#26 APBT

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Posted 21 March 2012 - 11:10 PM

Michael

A few questions regarding your use of arginine and lysine as AGE scavengers.

Like clockwork, you dose 40 minutes before meals. How crucial is the timing? Is consumption say, 10 minutes before eating effective?

You don't list a preferred purveyor of lysine or arginine. What is your current brand of choice?

Thoughts on "high-end, pharmaceutical grade" such as this. Worth the extra cost?
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#27 Michael

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Posted 22 March 2012 - 12:27 AM

A few questions regarding your use of arginine and lysine as AGE scavengers.


In consideration of discussions earlier in the thread, I've dropped the arginine.

Like clockwork, you dose 40 minutes before meals. How crucial is the timing? Is consumption say, 10 minutes before eating effective?


My hunch is not. Have a look at this finedy-dinedy graph on the pharmacokinetics (from (1)):

Posted Image

First, it's going to take a significant am't of time just to have that lysine up in your plasma: I want it at peak levels thru'out the postprandial period, if possible. Second, you can see that there is what I take to be a real depression in plasma levels when it's taken concomitantly with glucose; I take it that something similar would happen if it was taken shortly before a meal, and might even be further slowed by being mixed in with food. Third, in the rodent studies, they were in fact administered the stuff in tap water, meaning they had it coursing around much of the time even when not eating.

vYou don't list a preferred purveyor of lysine or arginine. What is your current brand of choice?

Thoughts on "high-end, pharmaceutical grade" such as this. Worth the extra cost?


My view has been that it's a commodity item with no particular history of adulteration, so I'd buy it from any reputable source. However, as it happens, after first my creatine experience (above), and just recently a quite similar experience with Ajinomoto's glycine powder (the taste is sweeter and 'cleaner' than any other brand I've used), and in recollection of the tryptophan-related outbreak of eosinophilia-myalgia syndrome (EMS) in 1989, I'm considering making the switch.

Reference
1: Kalogeropoulou D, LaFave L, Schweim K, Gannon MC, Nuttall FQ. Lysine ingestion markedly attenuates the glucose response to ingested glucose without a change in insulin response. Am J Clin Nutr. 2009 Aug;90(2):314-20. Epub 2009 Jun 24. PubMed PMID: 19553295.
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#28 APBT

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Posted 22 March 2012 - 07:47 PM

Michael

First, thank you for your quick post reply.

With the void created by discontinuing the arginine, I see you increased your lysine by only 0.5 g.

In the discussion portion of the study you link, the mean lysine dose was 11 g. In your newly revised protocol you're dosing with 1 g three times daily (previously 2.5 g total). How did you conclude 3 g was effective, if not optimal?

Lysine in this study was given at a high dose (mean 11 g). Others have reported that lysine, when given at more physiologic doses (between 1 and 5 g/d), did not have an effect on insulin secretion (13, 14). These studies did not evaluate the effect of the combination of lysine with glucose. Thus, it will be of interest to examine whether lysine attenuates the glucose response when ingested at lower doses using the current protocol.


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#29 Michael

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Posted 22 March 2012 - 08:07 PM

With the void created by discontinuing the arginine, I see you increased your lysine by only 0.5 g.

... on alternate days: I nix out an additional 1.5 g when doing resistance training (see original post).

In the discussion portion of the study you link, the mean lysine dose was 11 g. In your newly revised protocol you're dosing with 1 g three times daily (previously 2.5 g total). How did you conclude 3 g was effective, if not optimal?


I linked that study for its pharmacokinetic data: I am not taking lysine for the purpose in that study (lowering post-challenge glucose), tho' that's an intriguing possibility: I'm taking it (primarily) as a carbonyl scavenger (see original post). The dose I use is substantially more than was used in human trials for this purpose, and in rodent studies after adjustment for allometric scaling.

Edited by Michael, 22 March 2012 - 08:07 PM.

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#30 APBT

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Posted 11 April 2012 - 07:18 PM

Michael

A couple of follow-up question regarding lysine (and arginine) as AGE scavengers.

Would one's body weight and/or caloric consumption affect the dosing protocol? That is, if one weighed more than you and/or consumed more calories would you adjust the 1 g pre-meal lysine dose? If so, by how much?

You appear to consistently eat thrice daily. If one were eating five time daily would you advise dosing before each of those five meals?
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