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Very High Vitamin D, Atrial Fibrillation Link

supplement risks

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#1 Michael

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Posted 06 December 2011 - 01:46 AM


Circulation. 2011 Nov 22; 124(21 Suppl): A14699

Vitamin D Excess Is Significantly Associated with Risk of Atrial Fibrillation

Megan B Smith1; Heidi T May2; Tami L Blair3; Jeffrey L Anderson2; Joseph B Muhlestein2; Benjamin D Horne2; Donald L Lappe2; John D Day2; Brian G Crandall2; Peter Weiss2; Jeffrey S Osborn2; Thomas J Bunch2

... A total of 132,000 ["Patients of a large integrated healthcare organization without a prior diagnosis of [atrial fibrillation (AF)] who received 25[OH] Vit D measurements as part of their clinical care"] were studied, which averaged 52.0±19.4 years in age; 28.7% were male. ["Multivariable Cox hazard regression analysis (mean length of follow-up: 584.4±494.7 days) was used to evaluate 25[OH] Vit D categories for incident AF (determined by ICD-9 codes)."]

AF was diagnosed in 1.7%, 1.4%, 1.4%, 1.7%, 0.8%, and 3.8% for 25[OH] Vit D categories of 100 (p-trend100 predicted a significantly increased risk of incident AF (adjusted HR=2.51, p=0.003). In comparison, low 25[OH] Vit D (<20) did not confer a greater risk of incident AF (adjusted HR=1.14, p=0.08), despite associating with a higher prevalence of comorbities (i.e., hypertension, heart failure, diabetes, and renal failure).

Discussion: In this large system-wide population, 25[OH] Vit D excess is associated with a significant independent risk of incident AF. Further studies should validate this observation, explore the mechanisms of AF risk, and define safety margins for 25[OH] Vit D supplement use.
Posted Image

Although they repeat it several times, I have to assume that they actually mean ng/mL, not ng/dL. [Edit: I have now confirmed with the senior investigator, Jared Bunch, that they do, indeed, mean ng/mL].

See also their press release:

T. Jared Bunch, MD, a heart rhythm specialist at the Intermountain Medical Center Heart Institute and lead investigator on the study, says the findings are significant because so many Americans use vitamin supplements to promote their health.

"There are both benefits and harm to taking vitamin supplements of all kinds," says Dr. Bunch. "Our goal is to determine a safe dose and usage range so patients can understand what amount is healthy, and what amount may be toxic." [...]

The Institute of Medicine currently advises that healthy adults should be able to take as much as 4000 IU (international units) of vitamin D daily. But the reality is that doctors don't yet know how much vitamin D causes toxicity, which is why Dr. Bunch says communication between a patient and their healthcare provider is critical. [...]

Dr. Bunch stresses that patients need to tell their doctors about all of the vitamins and supplements they take, as well as all medications, in order to ensure they get the best care possible. He says this research also suggests that checking blood levels of vitamin D in patients that develop atrial fibrillation may help uncover the cause of the abnormal heart rhythm disorder.
"Patients don't think of vitamins and supplements as drugs," says Dr. Bunch. "But any vitamin or supplement that is touted as 'healing' or 'natural' is a drug and will have effects that are both beneficial and harmful. Just like any therapy, vitamins need to be taken for the right reasons and at the right doses."

This is loosely consistent with the rest of the prospective epidemiology, which supports some reduction in total mortality for 25(OH)vitamin D levels up to ~30-40 ng/mL, the level deemed 'sufficient' by Holick and others, but flattens thereafter, and (in Melamed et al, one of a very small number of studies -- and perhaps the only one? reporting total mortality for levels significantly higher than this) and showing a nonsignificant hint of an increase in mortality at higher levels:

Posted Image

Edited by Michael, 18 December 2011 - 10:43 PM.

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#2 TheFountain

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Posted 06 December 2011 - 02:00 AM

So someone would have to take about 9000 IUs or more, persistently for many months to reach the blood levels sited in this study?

9.600 IU Vitamin D Required to Get 97.5% of a Study Population to Serum 25(OH)D Levels of At Least 40ng/ml


I refrained from posting each and every study on vitamin D that has been published within the past weeks - nothing new or exciting there + way too much hype, if you want my opinion... BUT now, finally, there is some additional large-scale scientific data on the issues of how much is enough and how much is too much of supplemental vitamin D!

In the latest issue of Anticancer Research Garland et al. (Garland. 2011) published a study in which self-reported supplemental vitamin D intake in a cohort of 3,667 men and women from different ethnic backgrounds was assessed and corresponding serum vitamin D levels were measured. Posted Image Figure 1: Reported daily intake of vitamin D vs. measured serum 25(OH)D levels in study cohort of 3,667 subjects (Garland. 2011)
Unsurprisingly, "serum 25(OH)D rose as a function of self-reported vitamin D supplement ingestion in a curvilinear fashion", but other than some fear mongers would have us believe, ...

no intakes of 10,000 IU/d or lower producing 25(OH)D values above the lower-bound of the zone of potential toxicity (200 ng/ml).

While you, as a regular visitor of the SuppVersity, already knew that doses up to 10,000 IU are generally save, this is probably the first time you read a reliable number on how much supplemental vitamin D it takes to bring 25(OH)D levels to >=40ng/ml (which is even below the concentration of 60-80ng/ml, where scientists believe the anti-cancer effects of vitamin D set in):

The supplemental dose ensuring that 97.5% of this population achieved a serum 25(OH)D of at least 40 ng/ml was 9,600 IU/d.

In view of the authors conclusion that even "universal intake of up to 40,000 IU vitamin D per day is unlikely to result in vitamin D toxicity", and under the assumption that your vitamin D levels, as measured by blood tests, are low, you better invest in some high dose vitamin D supplements if you do not want to pop dozens of pills everyday.

http://suppversity.b...to-get-975.html
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#3 Michael

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Posted 06 December 2011 - 02:14 AM

So someone would have to take about 9000 IUs or more, persistently for many months to reach the blood levels sited in this study?

9.600 IU Vitamin D Required to Get 97.5% of a Study Population to Serum 25(OH)D Levels of At Least 40ng/ml [...]

In the latest issue of Anticancer Research Garland et al. (Garland. 2011) published a study in which self-reported supplemental vitamin D intake in a cohort of 3,667 men and women from different ethnic backgrounds was assessed and corresponding serum vitamin D levels were [...]

http://suppversity.b...to-get-975.html

No: as the abstract and press report both say, this is the amount required to get 97.5% of the population there. As with most nutrient requirements, there is a bell curve: most people will need far less than this. You can see in the Figure that lots of people are around 30-40 ng/mL at doses at or below 1000 IU. I avoid the sun pretty carefully, and my levels have consistently been >40 ng/mL at 800-1000 IU for years.

Edited by Michael, 06 December 2011 - 02:14 PM.

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#4 TheFountain

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Posted 06 December 2011 - 02:23 AM

So someone would have to take about 9000 IUs or more, persistently for many months to reach the blood levels sited in this study?

9.600 IU Vitamin D Required to Get 97.5% of a Study Population to Serum 25(OH)D Levels of At Least 40ng/ml [...]

In the latest issue of Anticancer Research Garland et al. (Garland. 2011) published a study in which self-reported supplemental vitamin D intake in a cohort of 3,667 men and women from different ethnic backgrounds was assessed and corresponding serum vitamin D levels were [...]

http://suppversity.b...to-get-975.html

No: as the abstract and press report both say, this is the amount required to get 97.5% of the population there. As with most nutrient requirements, there is a bell curve: most people will need far less than this. You can see in the Figure that lots of people are around 30-40 ng/mL at doses at or below 1000 IU. I avoid the sun pretty carefully, and my levels have consistently been >40 ng/mL at 800-100 IU for years.


Nice. how many IUs are you currently taking daily? 1000? I am considering lowering my vitamin d intake as well. I am currently at 3000 IUs and have been feeling light headed from time to time. But my last heart monitor reading revealed no abnormalities, atrial or otherwise. And my blood pressure was perfect. This was about 5 days ago, and I was hooked up to the monitor for about 25 minutes.

Edited by TheFountain, 06 December 2011 - 02:25 AM.


#5 steampoweredgod

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Posted 06 December 2011 - 03:00 AM

Isn't the body estimated to generate about 10,000 IU per day with large body exposure. If an individual spends an entire day indoor with non-uv-generating lighting I would assume that up to that amount would not cause trouble.

That said some sites say 2000iu could cause trouble, and for some reason the upper tolerable limit has been set at 4000iu not sure why.

Lef seems to recommend blood levels above 50 ng/mL, and to that end doses of 5000iu allow 97.5% to reach such.

#6 TheFountain

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Posted 06 December 2011 - 03:59 AM

Isn't the body estimated to generate about 10,000 IU per day with large body exposure. If an individual spends an entire day indoor with non-uv-generating lighting I would assume that up to that amount would not cause trouble.

That said some sites say 2000iu could cause trouble, and for some reason the upper tolerable limit has been set at 4000iu not sure why.

Lef seems to recommend blood levels above 50 ng/mL, and to that end doses of 5000iu allow 97.5% to reach such.


Re-read michaels post, he says that 800 IUs should be adequate to reach 40 ng, enough to get the blood levels up to allow protective benefits.

#7 nameless

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Posted 06 December 2011 - 04:38 AM

Interesting...

One thing I notice that appears odd at first glance -- why is there an increase in Afib at the 61-80 level, yet a decrease at 81-100? Numbers significant there?

As for dosing, serum D is of course highly variable per person. Stating 800IU will bring you to a certain level, or 5000IU is needed to reach 50 ng/mL, may work in general for large group studies, but I wouldn't use those numbers individually. Simply get serum D checked and then you know how much to take. 2000IU/daily, for instance, just gets me to the low 30s.

#8 JChief

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Posted 06 December 2011 - 07:05 AM

I think Vitamin D, A & K2 are all important. Cod liver oil combines all of them and toxicity studies that isolate a single vitamin are nice but I'd be curious how the presence other vitamins, such as Vitamin A, might offset some of the risk. "Nevertheless, what we need in order to show that levels higher than 50 ng/mL are helpful or harmful are vitamin D supplementation trials comparing the effect of different doses resulting in different blood levels on clinical health outcomes, and similar studies examining the interactions between vitamin D and the other fat-soluble vitamins."

Edited by JChief, 06 December 2011 - 07:08 AM.


#9 Michael

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Posted 06 December 2011 - 03:13 PM

Isn't the body estimated to generate about 10,000 IU per day with large body exposure. If an individual spends an entire day indoor with non-uv-generating lighting I would assume that up to that amount would not cause trouble.

That's really not a good basis for making such an assumption. There's no particular reason to assume that what you get in the 'natural world' is optimal: like much of the argument for Paleo dieting, it's adaptationist fallacy.

That said some sites say 2000iu could cause trouble, and for some reason the upper tolerable limit has been set at 4000iu not sure why.

From the IOM report, they based it on caution for uncertainty, plus the data on total mortality, which was more extensive than Melamed et al (I'd forgotten about Jie, and wasn't familiar with the others):

The ULs for vitamin D were especially challenging because available data have focused on very high levels of intake that cause intoxication and little is known about the effects of chronic excess intake at lower levels. ... The observation that 10,000 IU (250 μg) of vitamin D per day was not associated with classic toxicity served as the starting point for adults ... The conditions associated with the intoxication syndrome for calcium and vitamin D are informative, but avoiding acute toxicity is not the ideal basis for a UL, a reference value with the larger purpose of public health protection over a life time of chronic intake. ... [Therefore,] this value was corrected for uncertainty by taking into consideration emerging data on adverse outcomes (e.g., all-cause mortality), which appeared to present at intakes lower than those associated with classic toxicity and at serum 25OHD concentrations previously considered to be at the high end of physiological values. ...

cohort studies ... indicated that low serum 25OHD levels akin to deficiency states (< 30 nmol/L) are associated with an increased risk of mortality. Further, as serum 25OHD levels increase—up to a point—mortality is lowered. However, some, but not all, of the studies have observed a troubling U-shaped (or perhaps more appropriately a reverse-J-shaped) relationship. For example, Jia et al. (2007) found a statistically significant trend between increasing serum 25OHD levels and lower odds ratios for all-cause mortality (p = 0.03); however, a U-shaped or reverse-J-shaped relationship between serum 25OHD level and mortality was observed, with the lowest mortality at serum 25OHD levels below 50 nmol/L [20 ng/mL].

Posted Image


Visser et al. (2006) showed a similar pattern, with reduced mortality associated with higher than deficiency levels, but increased mortality at the highest blood 25OHD levels.

Posted Image



Melamed et al. (2008) ... also suggested a U-shaped or reverse-J-shaped risk curve with increasing risk at about 75 nmol/L
Posted Image

... Sambrook et al. (2004, 2006) found no relationship between mortality and the log of serum 25OHD levels in a sample (n = 842) of frail, institutionalized persons, most over the age of 80 years. ... In addition ... a preliminary analysis of NHANES III data limited to data on non-Hispanic blacks with follow-up as of December 31, 2006, also saw a U-shaped relationship, although the suggested increase in risk was seen at a lower serum 25OHD concentration of approximately 60 nmol/L [24 ng/mL] ["Personal communication, R. Durazo-Arvizu, Loyola University, Maywood, IL, May 28, 2010."].


Lef seems to recommend blood levels above 50 ng/mL, and to that end doses of 5000iu allow 97.5% to reach such.

Re-read michaels post, he says that 800 IUs should be adequate to reach 40 ng, enough to get the blood levels up to allow protective benefits.

Re-read Michael's post ;) . I did not say that: I said that in the Garland study, the graph suggests that "lots of people are around 30-40 ng/mL at doses at or below 1000 IU." The whole point about their study is that people vary in terms of how much they need, based on sunlight exposure, age, obesity, etc etc. Here is a review and several studies showing that average people don't quite break 30 ng/mL with doses in that range -- but of course, some individuals do:
http://edrv.endojour...t/22/4/477.long
http://jcem.endojour...nt/93/3/677.ful
http://www.ajcn.org/....expansion.html

See, similarly, Table 2 this review by Dawson-Hughes and Vieth:
http://www.direct-ms...timal%2025D.pdf

On this subject, here is more from the Garland et al study:

The 95% probability bands in Figure 2 provide useful information on the dosages required to ensure that a specified fraction of the population would have 25(OH)D concentrations above any given level. Such inferences are not affected by the cross-sectional character of the data. The points where that lower band crosses 30, 40, and 50 ng/ml (75, 100, and 125 nmol/l) are the supplemental intake values that ensure that 97.5% of the population would be above the specified serum 25(OH)D concentrations concerned. These are, respectively, 6,100, 9,600, and 14,100 IU/d for this population. Observed mean (SD) 25(OH)D concentrations at these intakes are, respectively 64.6 (±18), 75.1 (±18), and 85.2 (±18) ng/ml.


I did, however, say that 40 ng/mL is plenty, and indeed, probably the high end of healthy. IAC, test, don't guess.

LEF, IAC, are irresponsible.

One thing I notice that appears odd at first glance -- why is there an increase in Afib at the 61-80 level, yet a decrease at 81-100? Numbers significant there?

I'm assuming it's just noise; the proper publication would be needed to see for sure.

Simply get serum D checked and then you know how much to take. 2000IU/daily, for instance, just gets me to the low 30s.

Have you several tests to confirm that? It does take several months to reach steady-state.

I think Vitamin D, A & K2 are all important. Cod liver oil combines all of them and toxicity studies that isolate a single vitamin are nice but I'd be curious how the presence other vitamins, such as Vitamin A, might offset some of the risk.

Definitely not a good tradeoff in the case of cod liver oil. Numerous epidemiological studies, most of them prospective, report that high preformed vitamin A (not carotenoids), in several cases derived from the use of cod liver oil in Nordic countries to achieve even very conservative vitamin D doses, leads to elevated fracture risk and/or low BMD.

References
1 Melhus H, Michaelsson K, Kindmark A, et al. Excessive dietary intake of vitamin A is associated with reduced bone mineral density and increased risk for hip fracture. Ann Intern Med. 1998 Nov 15;129(10):770-8.

2 Feskanich D, Singh V, Willett WC, Colditz GA. Vitamin A intake and hip fractures among postmenopausal women. JAMA. 2002 Jan 2;287(1):47-54.

3 Opotowsky AR, Bilezikian JP. Serum vitamin A concentration and the risk of hip fracture among women 50 to 74 years old in the United States: A prospective analysis of the NHANES I follow-up study. Am J Med. 2004 Aug 1;117(3):169-74.

4 Promislow JH, Goodman-Gruen D, Slymen DJ, Barrett-Connor E. Retinol intake and bone mineral density in the elderly: the Rancho Bernardo Study. J Bone Miner Res. 2002 Aug;17(8):1349-58.

5 Michaelsson K, Lithell H, Vessby B, Melhus H. Serum retinol levels and the risk of fracture. N Engl J Med. 2003 Jan 23;348(4):287-94.

6 Freudenheim JL, Johnson NE, Smith EL. Relationships between usual nutrient intake and bone mineral content of women 35-65 years of age: longitudinal and cross-sectional analysis. Am J Clin Nutr. 1986 Dec;44(6):863-76.

7 Forsmo S, Fjeldbo SK, Langhammer A. Childhood cod liver oil consumption and bone mineral density in a population-based cohort of peri- and postmenopausal women: the Nord-Trondelag Health Study. Am J Epidemiol. 2008 Feb 15;167(4):406-11. Epub 2007 Nov 21. PubMed PMID: 18033763.

Edited by Michael, 18 December 2011 - 10:45 PM.

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#10 nameless

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Posted 06 December 2011 - 06:17 PM


Simply get serum D checked and then you know how much to take. 2000IU/daily, for instance, just gets me to the low 30s.

Have you several tests to confirm that? It does take several months to reach steady-state.


I have several years worth of tests to confirm that. Although the 2K number may apply more to Winter than Summer months somewhat -- I could probably knock off a couple hundred IU to get that same serum levels during Summer (sometimes).

#11 medievil

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Posted 07 December 2011 - 12:23 AM

Hmm when i took an anual dose of vitamin D last year i noticed this afterwards.

#12 DukeNukem

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Posted 07 December 2011 - 02:55 AM

That's really not a good basis for making such an assumption. There's no particular reason to assume that what you get in the 'natural world' is optimal: like much of the argument for Paleo dieting, it's adaptationist fallacy.


Other than CR, I think paleo has proven itself to give the best indications of health (through appearance and testing) versus any other diet. The evolutionary explanation gives the paleo diet (and lifestyle) a foundation based in science. But the most important thing is that it gives outstanding health results, as shown by the very many of us who do quite extensive blood work. Plus, it appears that most relevant diet studies support paleo-style eating.

However, as a strong advocate of a higher-fat paleo diet, I definitely deviate from the pack in numerous areas where I think longevity odds can be improved. The key facets of paleo that I embrace:

no wheat -- and almost no grains period
no plant oils with a PUFA content over 10%.
no processed sugars
no low fat foods
most protein and fats from animal sources
(In a nutshell, the three foodstuffs I avoid: fructose, gluten, most plant oils)

A lot of paleo people eat too many nuts, but I do not (too high in PUFAs)
A lot of paleo people avoid dairy, but I do not
I take a LOT of supplements, while most paleo people only take a few at most
I supplement with hormones, which I believe is very rare in the paleo community

I'll put my blood work up against any vegetarian. CR people are the only ones who have a chance to beat me, but I do not want to live a CR life, and I'm not sure much is to be gained by doing so. Especially for CRers who still eat poorly (such as including wheat in their diet).
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#13 JChief

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Posted 07 December 2011 - 04:36 PM

I think Vitamin D, A & K2 are all important. Cod liver oil combines all of them and toxicity studies that isolate a single vitamin are nice but I'd be curious how the presence other vitamins, such as Vitamin A, might offset some of the risk.

Definitely not a good tradeoff in the case of cod liver oil. Numerous epidemiological studies, most of them prospective, report that high preformed vitamin A (not carotenoids), in several cases derived from the use of cod liver oil in Nordic countries to achieve even very conservative vitamin D doses, leads to elevated fracture risk and/or low BMD.

I have somewhat of a retort! Also, in regard to your stance on no evidence that food from the natural world is best. I think it's instinctual personally. You just might be over-thinking it. :)

Edited by Michael, 10 December 2011 - 09:35 PM.


#14 steampoweredgod

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Posted 08 December 2011 - 04:59 AM

That's really not a good basis for making such an assumption. There's no particular reason to assume that what you get in the 'natural world' is optimal

Wasn't the recent evolution of light skin an adaptation to produce more vitamin D, and don't dark skinned individuals in northern regions experience deficits?

In any case while it might not be optimal, my comment was directed at such quantity being dangerous, after all 2000iu was considered dangerous and 4000iu is now the limit. Talks elsewhere of severe and permanent damage at levels below 10,000iu seem alarmist, and that's what I was trying to address

" The whole point about their study is that people vary in terms of how much they need, based on sunlight exposure, age, obesity, etc etc. Here is a review and several studies showing that average people don't quite break 30 ng/mL with doses in that range

Which is in line with my comments regarding supplementation, if you're not even near windows and with non-uv lighting for the entire day 5000iu seems reasonable.

Since just a few tens of minutes is generally enough to generate sufficient vitamin D in light skinned individuals, lower doses may be appropriate if any kind of sun exposure occurs.

Test, don't guess.

LEF, IAC, are irresponsible.

The LEF findings are supposedly based on blood test results from supplementing members. Assuming honesty, we must assume something else has caused the conflict between tests.

A lot of paleo people eat too many nuts, but I do not (too high in PUFAs)

I think macadamias are an exception, and might be a viable nut.

#15 hamishm00

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Posted 08 December 2011 - 12:29 PM

The Duke does make an exception for macadamias if I remember his previous postings correctly.

#16 niner

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Posted 08 December 2011 - 02:06 PM

That's really not a good basis for making such an assumption. There's no particular reason to assume that what you get in the 'natural world' is optimal

Wasn't the recent evolution of light skin an adaptation to produce more vitamin D, and don't dark skinned individuals in northern regions experience deficits?

In any case while it might not be optimal, my comment was directed at such quantity being dangerous, after all 2000iu was considered dangerous and 4000iu is now the limit. Talks elsewhere of severe and permanent damage at levels below 10,000iu seem alarmist, and that's what I was trying to address


Depends what you mean by dangerous. 10,000iu wouldn't kill you immediately, but it might raise your odds of A-fib or prostate cancer. Personally, I want to hit the sweet spot. I think the 25-OH-D level that is the sweet spot will be different for different people, depending on their other CVD and cancer risk factors.

" The whole point about their study is that people vary in terms of how much they need, based on sunlight exposure, age, obesity, etc etc. Here is a review and several studies showing that average people don't quite break 30 ng/mL with doses in that range

Which is in line with my comments regarding supplementation, if you're not even near windows and with non-uv lighting for the entire day 5000iu seems reasonable.


There's a huge complication due to the existence of crappy dry formulations with poor bioavailability. If it's a good formulation, 5000iu would put me at a level that I don't want to be at, even if I lived in a cave. But that's just me.
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#17 DukeNukem

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Posted 08 December 2011 - 06:43 PM

The Duke does make an exception for macadamias if I remember his previous postings correctly.


Yup. Macadamia nuts have a very similar fatty acid profile to EVOO -- both a around 10% PUFA content, which I find acceptable. Most nuts are around 50% or higher PUFA content. The plant oils I'll consume are:

EVOO
avocado oil (far far better cooking oil that EVOO, btw)
tea tree oil (although I do not use this -- don't like the taste)
coconut and palm oil
macadamia nut oil

I think that's all.

BTW, I sometimes cheat eating potato chips, but only because I found these, cooked in avocado oil:
http://www.amazon.co...ef=pd_sim_hpc_2
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#18 JChief

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Posted 09 December 2011 - 06:12 AM

The Duke does make an exception for macadamias if I remember his previous postings correctly.


Yup. Macadamia nuts have a very similar fatty acid profile to EVOO -- both a around 10% PUFA content, which I find acceptable. Most nuts are around 50% or higher PUFA content. The plant oils I'll consume are:

EVOO
avocado oil (far far better cooking oil that EVOO, btw)
tea tree oil (although I do not use this -- don't like the taste)
coconut and palm oil
macadamia nut oil

I think that's all.

BTW, I sometimes cheat eating potato chips, but only because I found these, cooked in avocado oil:
http://www.amazon.co...ef=pd_sim_hpc_2


No olive oil? Shame.

Edit: http://beyondhealth....eOilScandal.pdf

Double edit: You don't have to purchase it from Beyond Health but the message is what's important. Most olive oil these days are a waste, fraudulent & even toxic if you're not careful. I did some research and if you want to cut costs and go straight to the quality source the article refers to it's Bariani . :)

Edited by JChief, 09 December 2011 - 06:37 AM.


#19 Sillewater

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Posted 22 December 2011 - 02:57 AM

Am J Clin Nutr. 2011 Dec 14. [Epub ahead of print]


Vitamin D deficiency and mortality risk in the general population: a meta-analysis of prospective cohort studies.

Zittermann A, Iodice S, Pilz S, Grant WB, Bagnardi V, Gandini S.



Posted Image



and this yielded 14 prospective cohort studies that involved 5562 deaths out of 62,548 individuals.



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.



#20 Michael

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Posted 22 December 2011 - 04:06 AM

[quote name='DukeNukem' timestamp='1323226506' post='489766'][quote name='Michael' timestamp='1323184408' post='489608']That's really not a good basis for making such an assumption. There's no particular reason to assume that what you get in the 'natural world' is optimal: like much of the argument for Paleo dieting, it's adaptationist fallacy.[/quote]
Other than CR, I think paleo has proven itself to give the best indications of health (through appearance and testing) versus any other diet. The evolutionary explanation gives the paleo diet (and lifestyle) a foundation based in science. But the most important thing is that it gives outstanding health results, as shown by the very many of us who do quite extensive blood work. Plus, it appears that most relevant diet studies support paleo-style eating.[/quote]
If, for the sake of argument, Paleo eating did lead to the best blood work, then that would be a reasonable empirical basis for taking it up (tho' I suspect we disagree on what constitutes 'the best blood work,' and I'd point out that the cardiovascular disease meta-analyses would arguably rebut surrogate marker studies anyway). I was pointing out here that it's silly to argue that because our Paleolithic ancestors ate or didn't eat something, it must therefore be good or bad for us, rather than arguing from actual, empirical data.

[quote name='DukeNukem' timestamp='1323226506' post='489766']CR people are the only ones who have a chance to beat me, but I do not want to live a CR life, and I'm not sure much is to be gained by doing so. Especially for CRers who still eat poorly (such as including wheat in their diet).[/quote]
Duke, is it your impression that many CR people have significant amounts of wheat in their diet? You put several comments up on April's blog some years back that seemed to suggest that you thought she ate them all the time, when in fact they're occasional indulgences on her part. I (and many CR folk) do eat MegaMuffins, but they're constructed out of stuff like almond flour, ground vegetables, and (for those on higher-protein regimes) protein powder: there's just over two grams of wheat bran, and a bit of rye flour, in a generous 240 Calorie Muffin; I assume you'd agree that that's harmless. Very few CR folk eat a lot of grains in their regular diet, though many do eat much more than April or I would.

[quote name='JChief' timestamp='1323275761' post='489865'][quote name='Michael' timestamp='1323184408' post='489608'][quote name='JChief' timestamp='1323155127' post='489553'] Vitamin A, might offset some of the risk. [/quote]
Definitely not a good tradeoff in the case of cod liver oil. Numerous epidemiological studies, most of them prospective, report that high preformed vitamin A (not carotenoids), in several cases derived from the use of cod liver oil in Nordic countries to achieve even very conservative vitamin D doses, leads to elevated fracture risk and/or low BMD.[/quote]
I have somewhat of a retort! [/quote]
That's a very interesting article and mostly very well-argued article, until it suddenly seems to go off the rails: he raises a whole bunch of possible rebuttals to the vitamin A risk, and systematically discards them, but then seizes on the fact that most of the risk in one study (Feskanich et al, which I would agree is one of the stronger ones) came from supplements -- seeming to ignore the fact, as I'd indicated, that in three of the studies are (again) from the consumption of cod liver oil.

[quote name='JChief' timestamp='1323275761' post='489865']Also, in regard to your stance on no evidence that food from the natural world is best. I think it's instinctual personally. You just might be over-thinking it. :)[/quote]
First, I didn't' say that food "from the natural world" (as opposed to highly-processed food) wasn't best (it generally is, although it's silly to make a cult of this) -- I said that "There's no particular reason to assume that what you get in the 'natural world' is optimal: in this case, arguing that because one can "generate about 10,000 IU per day with large body exposure... I would assume that up to that amount would not cause trouble".

Suppose, however, that you're right that Paleo thinking is 'instinctual'; I'd at least agree that it's intuitive. How do you know your instincts (or intuitions) are right? It's 'instinctual' to think that the world is flat, that the sun travels around the Earth, and that objects follow Aristotelian laws of motion. Our instincts are wrong ;) .


[quote name='Sillewater' timestamp='1324522633' post='492319']Am J Clin Nutr. 2011 Dec 14. [Epub ahead of print]


Vitamin D deficiency and mortality risk in the general population: a meta-analysis of prospective cohort studies.



Zittermann A, Iodice S, Pilz S, Grant WB, Bagnardi V, Gandini S.



Posted Image


[/quote]
I don't understand this figure. What is it intended to portray?

[quote name='steampoweredgod' timestamp='1323320343' post='490019'][quote]That's really not a good basis for making such an assumption. There's no particular reason to assume that what you get in the 'natural world' is optimal
[/quote]
Wasn't the recent evolution of light skin an adaptation to produce more vitamin D, and don't dark skinned individuals in northern regions experience deficits?[/quote]
Yes. And it was designed to do that when we only lived for 30 y on average and mostly died of infection, accident, and war.

[quote name='steampoweredgod' timestamp='1323320343' post='490019']In any case while it might not be optimal, my comment was directed at such quantity being dangerous, after all 2000iu was considered dangerous and 4000iu is now the limit. [/quote]
Because, as I noted, we have evidence that the serum levels that produces may be associated with higher total mortality, risk of atrial fibrillation, and possibly pancreatic and prostate cancer. Just because we survived it as a species under Neolithic conditions, doesn't mean it's good for us as individuals -- in general, or in a modern milieu.

[quote name='steampoweredgod' timestamp='1323320343' post='490019'][quote]" The whole point about their study is that people vary in terms of how much they need, based on sunlight exposure, age, obesity, etc etc. Here is a review and several studies showing that average people don't quite break 30 ng/mL with doses in that range [/quote]
Which is in line with my comments regarding supplementation, if you're not even near windows and with non-uv lighting for the entire day 5000iu seems reasonable.[/quote]
In the quote you reproduce above, I was referring to TheFountain's' comments about 800 IU, not yours about 5000.

[quote name='steampoweredgod' timestamp='1323320343' post='490019'][quote]LEF, IAC, are irresponsible.[/quote]
The LEF findings are supposedly based on blood test results from supplementing members. Assuming honesty, we must assume something else has caused the conflict between tests.[/quote]
Another misunderstanding. To be clear, I wasn't arguing about what they found in their supplementing members, and don't think they contradict what Garland et al found: I was pointing out that it's irresponsible to recommend that people target blood levels above 50 ng/mL.

#21 Sillewater

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Posted 22 December 2011 - 05:19 AM


Am J Clin Nutr. 2011 Dec 14. [Epub ahead of print]


Vitamin D deficiency and mortality risk in the general population: a meta-analysis of prospective cohort studies.




Zittermann A, Iodice S, Pilz S, Grant WB, Bagnardi V, Gandini S.



Posted Image


I don't understand this figure. What is it intended to portray?


Just a more recent meta-analysis showing that indeed at higher serum levels mortality risks increase. The results jive with the 30-40ng/ml results from the Melamed et al results.

#22 Michael

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Posted 22 December 2011 - 01:00 PM

Am J Clin Nutr. 2011 Dec 14. [Epub ahead of print]


Vitamin D deficiency and mortality risk in the general population: a meta-analysis of prospective cohort studies.

Zittermann A, Iodice S, Pilz S, Grant WB, Bagnardi V, Gandini S.


I don't understand this figure. What is it intended to portray?


Just a more recent meta-analysis showing that indeed at higher serum levels mortality risks increase. The results jive with the 30-40ng/ml results from the Melamed et al results.

Broadly speaking, that is consistent with what the abstract says (risk reduction extends as far as 77.5 nmol/L (31 ng/mL), but that doesn't seem to have any relationship to the figure. What is the figure graphing out? The dual X-axes don't seem reconcilable, and the Y-axis makes no sense (and isn't of mortality).

I am currently at 3000 IUs and have been feeling light headed from time to time. But my last heart monitor reading revealed no abnormalities, atrial or otherwise. And my blood pressure was perfect. This was about 5 days ago, and I was hooked up to the monitor for about 25 minutes.

But you're in your twenties. And what is your serum 25(OH)D3?

Edited by Michael, 22 December 2011 - 02:14 PM.


#23 JvA

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Posted 22 December 2011 - 03:16 PM

Wasn't the recent evolution of light skin an adaptation to produce more vitamin D, and don't dark skinned individuals in northern regions experience deficits?


Yes, Sweden have taken in lots of refugees from Somalia that have suffered extensively from vitamin D defiency. For many years, lots of children with autism was born in this group, a problem that was more or less non-existent before they moved to the dark north.

Since two years back this group has been recommended taking vitamin d supplements, and it seems to have solved the issue of new children being born with autism.
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#24 Sillewater

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Posted 22 December 2011 - 08:08 PM

Broadly speaking, that is consistent with what the abstract says (risk reduction extends as far as 77.5 nmol/L (31 ng/mL), but that doesn't seem to have any relationship to the figure. What is the figure graphing out? The dual X-axes don't seem reconcilable, and the Y-axis makes no sense (and isn't of mortality).


Yea I agree the way its presented is somewhat confusing, they could've collapsed the data an made it easier to read, but this is more representative of their methods. Since Vitamin D serum level is usually non-zero, a reference level had to be chosen for meta-analysis (if meta-analyzing alcohol its easier because there are non-drinkers), thus they want a reference category where the variation isn't to large (thus introducing less noise), and the lower reference category with a median of 27.5 nmol/L was chosen, thus with each datapoint in their analysis it wasn't an absolute value but the difference from the 27.5. I'll also paste their figure 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. Results are based on a total number of 59,231
individuals. 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.






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