Vitamin D: Don't Overdo a Good Thing

[circular]

Okay, here's something on-point by someone who seems to be rather reputable, although he needs an editor. He references a 2014 review that covered a number of D3 > endpoints, not including dementia specifically but including all cause mortality:

"Is Vitamin K2 the New Vitamin D?"

I do not know how this is going to work out, but I have a hunch that vitamin K2 will turn out to be a really big deal rather than only "the new vitamin D," with much fuss and little substance.

http://www.medscape.com/viewarticle/834763

The review paper:

Agency for Healthcare Research and Quality. Link between vitamin D and health outcomes unclear. Electronic newsletter., Issue 440. September 16, 2014. http://www.ahrq.gov/news/newsletters/e- ... r/440.html Accessed November 10, 2014.

Conclusions. In solid agreement with the findings of the original report, the majority of the findings concerning vitamin D, alone or in combination with calcium, on the health outcomes of interest were inconsistent. Associations observed in prospective cohort and nested case-control studies were inconsistent, or when consistent, were rarely supported by the results of randomized controlled trials. Clear dose-response relationships between intakes of vitamin D and health outcomes were rarely observed. Although a large number of new studies (and longer followups to older studies) were identified, particularly for cardiovascular outcomes, all-cause mortality, several types of cancer, and intermediate outcomes for bone health, no firm conclusions can be drawn. Studies identified for the current report suggest a possible U-shaped association between serum 25(OH)D concentrations and both all-cause mortality and hypertension and also suggest that the level of supplemental vitamin D and calcium administered in the Women’s Health Initiative Calcium-Vitamin D Trial are not associated with an increased risk for cardiovascular disease or cancer among postmenopausal women who are not taking additional supplemental vitamin D and calcium. Studies suggest the method used to assay 25(OH)D may influence the outcomes of dose-response assessments. Beyond these observations, it is difficult to make any substantive statements on the basis of the available evidence concerning the association of either serum 25(OH)D concentration, vitamin D supplementation, calcium intake, or the combination of both nutrients, with the various health outcomes because most of the findings were inconsistent.

Full text:

http://www.effectivehealthcare.ahrq.gov ... 140902.pdf

[Julie G]

Have we seen this paper before? It seems to indicate that higher serum Vitamin D levels are protective in E4 homozygotes, but NOT heterozygotes. I wonder what level the authors define as “higher”?

25-Hydroxyvitamin D, APOE ε4 genotype and cognitive function: findings from the 1958 British birth cohort

Among participants with two APOE ε4 alleles, higher 25(OH)D concentrations were associated with higher memory function, whereas in others, memory scores were slightly lower for individuals with higher versus lower concentrations.

[Julie G]

Here’s an interesting new study indicating that higher (above 50 ng/ml) may offer some protection against MS by correcting a hyper-immune response. http://dgnews.docguide.com/taking-vitam ... newsletter

I wonder if this could translate to minimizing dementia risk as E4 carriers also tend to also have a heightened immune response?

[Gilgamesh]

Have we seen this paper before?

Yup! And Stavia got it for us:

To supplement or not

Messy data: huge confidence intervals. (And see the rest of my response right after Stavia's post.)

G

[Julie G]

Thanks, G & (Stavia!) THOUGHT we had seen it before. Bad on me for not tracking it down.

I hear your concerns, G. And, yes, smaller sample sizes certainly generate wider confidence intervals…BUT (in E4 world) 144 homozygotes and 1174 heterozygotes is actually pretty impressive.

I encourage everyone to check out figure 1. I was unable to copy it here. For heterozygotes, a 25(OH) D concentration of 60 nmol/L was associated with the highest cognitive performance. (That's only 24 ng/mL.) Beyond that, cognitive performance drops off slightly. Interestingly -contradicting other evidence- E4 heterozygotes and other APOE genotypes maintained good cognition in middle age despite very low levels of 25 (OH) D, 10 nmol/L in this figure.

But, the picture is very different for E4 homozygotes. We exhibit significantly lower cognitive performance at a low 25(OH)D level- 10 nmol/L. In fact, there is a linear correlation with D level and cognition with the highest performance at 130 nmol/L. (That's 52 ng/mL.) Unfortunately, no higher levels were examined.

I'm wondering if we've seen other studies (correlating Vitamin D level and cognition that also examined APOE genotype) that contradict this? This one seems to provide some decent hints about optimal target levels. Too bad the issue of supplementation vs. the natural acquisition of vitamin D levels wasn't addressed.

[Jean]

Well, I've been supplementing 5000IU daily since testing at 17 in 2008. I was told low levels led to cancer, which easily led me to stay at this level for 7 years. I had been outdoors in the sun a lot, participated in outdoor sports. Colorado is sunny. In other words, I don't think sun had anything to do with my low level. So I reasoned that my genetics were pushing me toward an undesirable level .

What would you do if you were me? I'm 3/4, 68 yrs young. At this time my inclination is not to decrease my dose simply because it hasn't affected me adversely from what I can tell.

Blood tests:
D3 2008 17.2
D3 2009 67.7
D3 2012 66

From Forum posts:
One test inferred that I'm risking lower cognition at this level (66) as a 3/4. However, Bresden obviously disagrees.

Melatonin: I don't think my melatonin was affected, since sleeping soundly for 8 hrs hadn't been a problem.

Apod: Perhaps higher dosages of D3 is less likely to be "overdoing it" when regularly consuming an adequate intake of organ meats, eggs, and dairy fat rich in retinol and k2, with an adequate intake of calcium and magnesium. It seems fairly easy to under supply calcium, magnesium, boron, zinc, retinol, k1, and k2 in the diet, then supplement a ton of d3 leading to issues down the line.

(This sounds like me minus the organ meats.)

Juliefee: Here’s an interesting new study indicating that higher (above 50 ng/ml) may offer some protection against MS by correcting a hyper-immune response. http://dgnews.docguide.com/taking-vitam ... newsletter
I wonder if this could translate to minimizing dementia risk as E4 carriers also tend to also have a heightened immune response?

[Gilgamesh]

Julie, interesting speculation about the MS study! I'm starting to think that optimal levels for ε4s might be highly conditional: optimal for what? (And: for a 4/3, or for a 4/4?)

I still stand by my summary here. ("Standing" on one foot, with an only slightly leaky blindfold on, of course.) But, it could be that higher levels than that are better for dementia prevention, but worse for other things (cancer, osteoporosis, etc.). We just don't know. But I doubt it. The study of Hawaiian surfers impressed upon me that mother nature really does not want humans to have high levels of vitamin D. All that sun, all that healthy, young, white skin: the body just really, really strongly guards against letting blood vit. D levels get very high. Doing the math, without a powerful process for keeping the normal UV-induced vitamin D creation process from doing its thing at the normal rate, levels would shoot up to hundreds of ng/mL. Seems, to me, likely there's a very, very good reason the body evolved that powerful process. (1)

But, again: we don't know.

G

(1) It's tempting to speculate the outliers were 4/4s. A comforting thought, but nothing more than that. We need more research! (And the outliers only got to 60-65 or so -- and why should we expect the mechanism guarding against too much D to work perfectly?)

[Julie G]

Jean, we just don’t know . Lots of evidence suggests that a Vitamin D deficiency is associated with cognitive decline, but the definition of “deficiency” isn’t even agreed upon. The British cohort study is the first one I’ve seen that took APOE status into account when correlating D levels with cognition. We desperately need more research here.

The Hawaiian surfer study is interesting, G. I wonder if the participants were natives? Evidence shows that people with darker skin absorb less vitamin D than light skinned people: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3356951/

People with a naturally dark skin tone have natural sun protection and require at least three to five times longer exposure to make the same amount of vitamin D as a person with a white skin tone.

FWIW, I recently queried Dr. Bredesen on the references to back up his recommendations for maintaining levels of 50-80 ng/mL. His response:

Yes, I owe you more on vitamin D.  From a practical standpoint, I am just concerned that I repeatedly see levels from 16-25 ng/mL, unquestionably suboptimal.

The implication being that clinically levels below 25 ng/mL are associated with cognitive decline…

[Jean]

Thanks Julie - I meant to infer that I was a guinea pig of sorts because I have been on 5000IU for 8 years.
I do tan well (southern European.) background which may be why I didn't absorb more D3? Think I'll call my doctor tomorrow and ask for a D3 test. Haven't had one in awhile, and since my last test have increased my fish (salmon) intake dramatically. Currently it seems the prevailing medical opinion is that a toxic level is considered above 100 or 150.

And yes, Dr. Bresden owes us more for selecting that range. 'I'm thinking his comment of' 'I owe you more on that.' means he may have more information but it will probably not be definitive.

G Your conclusion makes sense to me: "The study of Hawaiian surfers impressed upon me that mother nature really does not want humans to have high levels of vitamin D." I wonder who naturally has 60-80 levels of D3? There must be some individuals in that range for that to be considered optimal by anyone.

[Tincup]

Rhonda Patrick says studies show U or J shaped curve above 60, Gundry is in Bredesen's camp and is happy with 100. I plan to query this the next time I talk to him later this month. My friends who looked at this in detail are happy with 70-100. I've not gotten details from them.