All:
Sorry for the long delay ... digging, and other responsibilities ...
On Mg form: just saw
this study, which (using the most comprehensive and reliable methodology to establish actual systemic bioavailability (in rats, not humans, but as they say there's little reason to expect much interspecies difference), which compared Mg from
oxide, chloride, sulphate, carbonate, acetate, pidolate, citrate, gluconate, lactate or aspartate. After 10 days of Mg-repleted diet ... Mg absorption values obtained varied from 50% to 67%. Organic Mg salts were slightly more available than inorganic Mg salts. Mg gluconate exhibited the highest Mg bioavailability of the ten Mg salts studied
That surprised me. FWIW, they didn't specifically test citrate or glycinate, but (again) Mg glycinate actually hasn't fared all that well, and heretofore the aspartate (the closest second in this study) has seemed best. Alas, gluconate is only 5.4% elemental Mg!
This study, in humans,
was a randomised, double-blind, placebo-controlled, parallel intervention, of 60 days duration. ["Subjects were only recruited if their dietary Mg intake was equal to the Reference Nutrient Intake (RNI) ± 20% ... 270 mg for women and 300 mg for men. "] Urine, blood and saliva samples were taken at baseline, 24 h after the first Mg supplement was taken ('acute' supplementation) and after 60 days of daily Mg consumption ('chronic' supplementation). Results showed that supplementation of the organic forms of Mg (citrate and amino-acid chelate [specific amino acid unspecified]) showed greater absorption (P = 0.033) at 60 days than MgO, as assessed by the 24-h urinary Mg excretion. Mg citrate led to the greatest mean serum Mg concentration compared with other treatments following both acute (P = 0.026) and chronic (P = 0.006) supplementation. Furthermore, although mean erythrocyte Mg concentration showed no differences among groups, chronic Mg citrate supplementation resulted in the greatest (P = 0.027) mean salivary Mg concentration compared with all other treatments. Mg oxide supplementation resulted in no differences compared to placebo [!]. We conclude that a daily supplementation with Mg citrate shows superior bioavailability after 60 days of treatment when compared with other treatments studied.
As I said, bioavailability is a bit of a bugaboo here, but citrate also has that much-more-reasonable 16% elemental Mg content.
I'd still strongly oppose MK-4-only. ... I think your concerns are overthrown by recent epidemiology. Long chain menaquinones are a must, 3 out of 4 observational studies found 'em to be superior to MK-4* and only one suggested similar efficacy, w/ MK-4 coming out on top. ... Natto and high intakes of phylloquinone may be casually linked to improved BMD/quality, I don't think such data exists for dietary-level MK-4. There are hardly any human or animal studies using low amounts (dietary) of MK-4 ... If anything, the epidemiology indeed supports a broad range of menaquinones (-4 and -7 & others).
Clickety-click ... PubMed ... clickety-click ... Google Scholar ... ... Yup, that does seem to be the best way to read the evidence on CVD, particularly since
EPIC is a much bigger and more widely-representative study than the
Rotterdam Study, tho' it looks to me like the apparent nonassociation in some cases is just
ad silentio, and there is teh caveat that most MK-4 comes from cheeses, which confounds MK-4 intake with saturated fat and AGE, whereas MK-7 is a marker of relatively healthy diets. For osteo, the pattern is the same, or stronger, tho' much of it is cross-sectional rather than prospective; also, the data are almost all Japanese, who in some regions get a lot of MK-7 thru' natto, and little to no 4, so it could just be not meeting a (quite low) threshold dose. Even if that's all correct, however, then (as you say) "If anything, the epidemiology indeed supports a broad range of menaquinones (-4 and -7 & others)" rather than any actual
advantage to using 4.
So, you go with what you've got, and clearly 7 is better-supported here at dietary intakes, caveats aside. Plus, it's happily much cheaper. And whoever picked 45 µg was doing hir homework, too. Good job, Kismet and Mystery (Wo)Man!
I do think that 500mcg K1 would be a good idea, but I'd not consider it very well supported by actual epidemiology or even teh paleo angle (did they really eat that many greens?)
Actually, yes, they did, but leaving that aside: I might suggest instead a small, DRI-level K1 (120 µg), which as you allulde is well below population intakes in both of the above studies and so should be both harmless and plenty for basic functions granted the DRI evidence base plus the inclusion of a high (population-level dietary) dose of MK-7.
Absolutely true, if someone is taking a full daily dose -- but they shouldn't be.
This may be a source of confusion. So let's make sure: Michael recommends not taking a full multi (and designing this multi w/ that in mind). AFAIK Ajna intended the "full" dose of this multi to be optimal (or as good as possible).
Well, you certainly can't have people taking
100% of their total daily nutritional requirements for most nutrients from a multi on top of what's in their diets, as would be the case with this multi if so, for the usual reasons. 100% of this multi would be a good idea for someone eating a diet composed entirely of protein powder, refined canola oil, and cornstarch -- but no one else.
For instance the vitamin D amount was chosen with that in mind (and IMHO represents the most conservative sweetspot there is).
Even there, some will not be getting enough -- but yes, it's a problem, and it's inescapable. As I've said many times, the whole multivitamin concept is fundamentally a very blunt instrument, and people shouldn't use them. If they "must," they still oughta use a part dose and then add on where still lacking, and vitamin D is the clearest case where that's just inescapable.
An even trickier case is iron: most males, especially omnivores, and postmenopausal women, get all the iron they need, and often too much, and certainly shouldn't be taking a supplement -- but many or even most women ≤ 55 and plenty of vegetarians could use (say) 50% DRI. Whatcha gonna do? (Happily, D and Fe are also amongst the few nutrients where there's a reliable functional marker to assess one's status).
On the flipside, this means that we should cut the amounts of several nutrients if we intend people to take the "full" dose.
I don't think that strategy quite makes sense, as no one will understand the label. The point of the multi should be to represent the perfect diet in a pill -- the old "Astronaut food" idea. You can't understand the targets and logic without seeing the pattern you're aiming for (which is revealed at the somewhat-misnamed "full daily dose").
So do we optimise the "full" dose or recommend people to adjust their intakes? (which many will fail to do...)
We can certainly can't
force people not to take a full dose, but we can do our best to educate them, which should get at least a few people acting intelligently (if nothing else, by rubbing their neurons together for a moment). If we design the product (or the label) so that the formula looks,
prima facie, somehow "incomplete" or "low-dose," they just won't buy it in the first place, ISTM.
There was some discussion of splitting the full dose into 2 or 3 caps, so that people can adjust their intake.
Well, first, we're not going to have any choice about splitting or no: if eg we're seriously going to put in 200 mg of mg as the glycinate, it's only 11% elemental, so that's 3 capsules right there. Even true citrate is only 16% (tho' a lot of shyster and/or ignorant suppliers will sell "blends," "complexes" etc that claim higher elemental Mg because they're mixed in with MgO), so that's 2. 550 mg choline (as bitartrate) will also take nearly 2 caps. This kind of thing is why A0R held our noses on the multis and used (and disclosed use of!) some MgO along with citrate and ascorbate (the latter largely to save a bit of space), and OrthoCore original was still 9 freakin' caps/d.
Imminst members who monitor their diet religiously, might only take 1/3 dose. Regular folks who buy it because all the "health-nuts" are taking it (and whose diets are probably lacking), could consume the full dose and get the benefits of a well-rounded best-current-science multi (no over-kill).
No, they won't, again for the op cit reason. Look, here is (some of) the nutrition in Mcdonald's Big Mac, French Fries (Large Serving), And Chocolate Triple Thick Shake, 21 fl oz:
General (83%)
=======================
Energy | 1820.5 kcal (!)
Vitamins (48%)
========================
Vitamin A | 1840.2 IU 61%
Retinol | 430.4 µg
Folate | 197.9 µg 40%
B1 (Thiamine) | 1.1 mg 90%
B2 (Riboflavin) | 1.5 mg 117%
B3 (Niacin) | 12.3 mg 77%
B5 (Pantothenic Acid)| 4.2 mg 83%
B6 (Pyridoxine) | 1.0 mg 61%
B12 (Cyanocobalamin) | 4.5 µg 187%
Vitamin C | 12.1 mg 13%
Vitamin D | 0.0 IU 0%
Minerals (66%)
========================
Calcium | 857.3 mg 86%
Copper | 0.6 mg 70%
Iron | 8.3 mg 103%
Magnesium | 168.8 mg 40%
Manganese | 1.0 mg 45%
Phosphorus | 967.1 mg 138%
Potassium | 2327.8 mg 50%
Selenium | 0.0 µg 0%
Sodium | 1692.8 mg 130%
Zinc | 7.2 mg 66%
Lipids (32%)
=======================
Saturated | 22.4 g
Omega-3 | 0.6 g 16%
Cholesterol | 145.1 mg 48%
This person clearly needs more nutrition, including ≥1000 IU of vitamin D, and might or might not need more Fe depending on gender and age, but should
not throw 100% DRI of everything else on top of that, even if that's all s/he eats all day -- and presumably (Dog help hir!), s/he's going to eat more food over the course of the day.
We're just stuck with this; ISTM the best course of action is to design the perfect Astronaut Food, and provide instructions to get as many people to act responsibly as possible -- or alternatively, to wash our hands of the whole multivitamin project, as (again) was my initial instinct.
-Michael
Edited by Michael, 13 December 2009 - 11:02 PM.