19 replies to this topic

[Sharpe]

Hi all,

 

Just bought vitamin D-3 from NOW foods 2000 iu.

Was wondering who is using vitamin d-3 and if there are any noticeable effects from it?

 

 

[Transcender]

I am using the same product. I can't say I feel anything different.

[pbandy1]

Don't notice a thing. Take 5000iu from LEF. Should probably get a blood test to see where I'm at. Vitamin D is one of those that if you are in a good blood range (goal is between 40-60ng/ml), your mood in the background seems to hum along nicely. Not to mention the vast health benefits.

[krillin]

When you look at all-cause mortality the optimum is more like 35 ng/ml.

[timar]

For me, keeping my vitamin D level above 30 ng/ml completely prevents any outbreak of the atopic dermatis I used to suffer from seasonally. I think it may also have a mood-stabilizing effect for me during the winter.

 

When you look at all-cause mortality the optimum is more like 35 ng/ml.

 

That's only an association. I have already explained - again and again - the profound confounding mechanisms that are most likely responsible for the increase in all-cause mortality observed at levels above 35 ng/ml.

 

 

Edited by timar, 29 October 2014 - 07:56 AM.

[Kalliste]

I've recently come across some studies using something called "Activated cholecalciferol" or maybe it was "Activated Vitamin D3". Googling is not helping me. The results from that seemed pretty positive, does anyone know what I'm talking about? Should we not be getting in on that good stuff?

[timar]

Sounds suspicious, I wouldn't buy it. It could refer to the storage form of vitamin D, 25-hydroxyvitamin D. This form should never be taken orally as in contrast to cholecalciferol, which is inherently safe up to very high doses, it can easily lead to non-physiologically high levels of vitamin D.

 

Btw. if someone disagrees with what I referenced above I would like to read his arguments instead of knowing only by the downvote.

[Kalliste]

Found it. Possibly not very relevant from a supplement pov. Good reason to take care of Vit D proactively though.

The poor clinical outcome in pancreatic ductal adenocarcinoma (PDA) is attributed to intrinsic chemoresistance and a growth-permissive tumor microenvironment. Conversion of quiescent to activated pancreatic stellate cells (PSCs) drives the severe stromal reaction that characterizes PDA. Here, we reveal that the vitamin D receptor (VDR) is expressed in stroma from human pancreatic tumors and that treatment with the VDR ligand calcipotriol markedly reduced markers of inflammation and fibrosis in pancreatitis and human tumor stroma. We show that VDR acts as a master transcriptional regulator of PSCs to reprise the quiescent state, resulting in induced stromal remodeling, increased intratumoral gemcitabine, reduced tumor volume, and a 57% increase in survival compared to chemotherapy alone. This work describes a molecular strategy through which transcriptional reprogramming of tumor stroma enables chemotherapeutic response and suggests vitamin D priming as an adjunct in PDA therapy.


http://www.cell.com/...8674(14)01033-2

[timar]

This paper mentions "activated pancreatic stellate cells", not "activated vitamin D" ...  they administered calcipotriol, a synthetic vitamin D (calcitriol) analogu that doesn't affect calcium metabolism nearly to the same degree as calcitriol does, so it can be given in extremely high doses without causing hypercalcemia. This is neither available over the counter nor would I recommend anyone to take it, except of course someone suffering from pancreatic cancer.

 

Fascniating paper, though, as it strongly adds to the mechanistic evidence for the cancer-protective effects of vitamin D.

Edited by timar, 29 October 2014 - 11:09 AM.

[Kalliste]

I think I mixed it up in my memory. The active form is probably the 25 hydroxy-stuff you mentioned earlier. I have digested a ton of papers on vitamin D trying to get dosage straight so memory is a mish-mash right now.

[Dan1976]

Vitamin D3 experiences:

When I took 5000 IU per day, I became very sleepy and slept many hours - up to 16 hours per day.

Taking only 2000 IU had no such effect, so this is how much I continue to take.

Never tested my blood levels. I will, someday.

Don't forget to take it with vitamins A and K2.

[krillin]

For me, keeping my vitamin D level above 30 ng/ml completely prevents any outbreak of the atopic dermatis I used to suffer from seasonally. I think it may also have a mood-stabilizing effect for me during the winter.

 

When you look at all-cause mortality the optimum is more like 35 ng/ml.

 

That's only an association. I have already explained - again and again - the profound confounding mechanisms that are most likely responsible for the increase in all-cause mortality observed at levels above 35 ng/ml.

 

It's not confounded by cholesterol. The 2008 paper by Melamed et al. found a similar U-curve and they controlled for a lot:

 

Covariates included in the final model were age, sex, race, season, hypertension, history of prior CVD, diabetes mellitus, smoking, BMI, HDL cholesterol, total cholesterol, the use of cholesterol-lowering medications, eGFR categories, serum albumin, log urinary albumin-creatinine ratio, log CRP, physical activity level, vitamin D supplementation and low SES.

In Framingham, cardiovascular disease risk was lowest for 20-25 ng/ml. This paper on a U-curve for 1,25-OH D and arterial thickening and calcification noted that vitamin D turns vascular smooth muscle cells into osteoblast-like cells, so we have a mechanism to explain the hazards of going too high.

[timar]

Now krillin, this is really evil study twisting, akin to the LEF's art, just to the other direction...

 

It's not confounded by cholesterol. The 2008 paper by Melamed et al. found a similar U-curve and they controlled for a lot:

 

First of all, controlling for cholesterol will not control for all the deleterious effects of genotypes like ApoE4. But anyway, they did not find a U-curve with any significance at the upper half. Such graphs are a dangerous thing to interpret - they led us to believe in a clear-cut association when in reality there are just some random dots remaining on a certain section of the graph. It's good that the authors at least included the confidence interval on that graph, so you can see that the lower limit doesn't change at all it the upper half.

 

Hence the authors' only conclusion:

 

The lowest quartile of 25(OH)D (<17.8 ng/ml) is independently associated with all-cause mortality in the general population.

 

The last paper you linked has the title: A Bimodal Association of Vitamin D Levels and Vascular Disease in Children on Dialysis - which should immediately raise the question whether those findings are actually applicable to the general population. Of course they are not. You probably know that the kidney has a pivotal role in vitamin D metabolism by producing the circulating "active" form of vitamin D, caltritiol. In healthy people this conversion is tightly regulated, but in renal disease it becomes aberrant, either producing too high or too low circulating levels of calcitriol. This is why the authors found that...

 

patients with both low and high 1,25(OH)₂D had significantly greater carotid intima-media thickness (P < 0.0001) and calcification (P = 0.0002) than those with normal levels. Low 1,25(OH)₂D levels were associated with higher high-sensitivity C-reactive protein (P < 0.0001). Calcification was most frequently observed in patients with the lowest 1,25(OH)₂D and the highest high-sensitivity C-reactive protein. In contrast, 25(OH)D levels did not correlate with any vascular measure.

 

Please note the last sentence as this is what we are talking about here when refering to vitamin D. You should know that the cited in vitro and animal studies showing increased calcification from "vitamin D" are again refering to the tighly controlled calcitriol. There are not studies showing increased calcification from 25(OH)D levels within the physiological range (<= 100 ng/ml).

 

Thus, although vitamin D [calcitriol] exerts potentially deleterious procalcific effects on the vasculature, its anti-inflammatory properties may confer a significant cardioprotective benefit. In this study, we hypothesize that 1,25(OH)₂D [calcitriol] levels in the normal range are associated with less vascular damage and calcification in children on dialysis.

 

Once again, calcitriol levels are always in the normal range in people without kidney diease and with at least adequate 23(OH)D.

Edited by timar, 30 October 2014 - 08:35 AM.

[krillin]

Now krillin, this is really evil study twisting, akin to the LEF's art, just to the other direction...

 

It's not confounded by cholesterol. The 2008 paper by Melamed et al. found a similar U-curve and they controlled for a lot:

 

First of all, controlling for cholesterol will not control for all the deleterious effects of genotypes like ApoE4. But anyway, they did not find a U-curve with any significance at the upper half. Such graphs are a dangerous thing to interpret - they led us to believe in a clear-cut association when in reality there are just some random dots remaining on a certain section of the graph. It's good that the authors at least included the confidence interval on that graph, so you can see that the lower limit doesn't change at all it the upper half.

 

Hence the authors' only conclusion:

 

The lowest quartile of 25(OH)D (<17.8 ng/ml) is independently associated with all-cause mortality in the general population.

 

It's not evil twisting, it's prudent supplementation practice. Risks should be assumed to be real regardless of statistical significance until the dose is proven to be actually beneficial. Benefits are the only effects that should be held to rigorous standards before believing and acting on them. The women above 50 ng/ml did have a statistically significant higher mortality rate in Figure 2, so it's prudent to assume that the Figure 1 U-curve should be taken seriously. What you have is a testable hypothesis, not a justification for pushing D above 40 ng/ml.

 

 

The last paper you linked has the title: A Bimodal Association of Vitamin D Levels and Vascular Disease in Children on Dialysis - which should immediately raise the question whether those findings are actually applicable to the general population. Of course they are not. You probably know that the kidney has a pivotal role in vitamin D metabolism by producing the circulating "active" form of vitamin D, caltritiol. In healthy people this conversion is tightly regulated, but in renal disease it becomes aberrant, either producing too high or too low circulating levels of calcitriol. This is why the authors found that...

 

patients with both low and high 1,25(OH)₂D had significantly greater carotid intima-media thickness (P < 0.0001) and calcification (P = 0.0002) than those with normal levels. Low 1,25(OH)₂D levels were associated with higher high-sensitivity C-reactive protein (P < 0.0001). Calcification was most frequently observed in patients with the lowest 1,25(OH)₂D and the highest high-sensitivity C-reactive protein. In contrast, 25(OH)D levels did not correlate with any vascular measure.

 

Please note the last sentence as this is what we are talking about here when refering to vitamin D. You should know that the cited in vitro and animal studies showing increased calcification from "vitamin D" are again refering to the tighly controlled calcitriol. There are not studies showing increased calcification from 25(OH)D levels within the physiological range (<= 100 ng/ml).

 

Thus, although vitamin D [calcitriol] exerts potentially deleterious procalcific effects on the vasculature, its anti-inflammatory properties may confer a significant cardioprotective benefit. In this study, we hypothesize that 1,25(OH)₂D [calcitriol] levels in the normal range are associated with less vascular damage and calcification in children on dialysis.

 

Once again, calcitriol levels are always in the normal range in people without kidney diease and with at least adequate 23(OH)D.

 

The patients were mostly highly deficient in vitamin D so I would have been surprised if they had found any harm from excessive 25D. Excessive 25D can cause harm by displacing 1,25D from the vitamin D binding protein or by increasing local production of 1,25D, so any harm that 1,25D can cause can theoretically also be caused by a high-enough level of 25D. Vascular smooth muscle cells are capable of making their own 1,25D, so you can't assume that being in the normal range of circulating 1,25D is sufficient to be safe from vascular calcification. Quote from the link:

 

 

because the Km for 1,25(OH)₂D₃ generation in VSMCs is ≈25 ng/mL of 25(OH)D₃, which is about the usual concentration of 25(OH)D₃ in humans, small changes in circulating 25(OH)D₃ may translate into large alterations in generated 1,25(OH)₂D₃.

 

[Tesla]

Every few days, I'll take 3 x 5000 IU of D3 from NOW foods with a fatty meal. I've been doing that for the past few years. Never had any negatives come from it.

Although, I did feel benefits when I first started taking it, as I had a severe Vitamin D deficiency. At the time, my blood glucose would spike to pre-diabetic levels ~40 minutes after eating, but return to normal levels at the 2-hour post-postprandial reading. Severe brain fog and depression were also present. I could also sleep for many hours on end, like 16+ hours straight.

 

After taking the Vitamin D3 for a few months (and getting adequate sun exposure), blood sugar stabilized to healthy levels, 8 hours of sleep was enough, and my brain fog was completely lifted. So I guess if you have a deficiency, Vitamin D will make you feel SO MUCH BETTER. 

[Skyguy2005]

No. I've never actually noticed anything from it.

[krillin]

I found a potential mechanism to explain the repeated association of 25D >40 ng/ml with increased pancreatic cancer. The level of CYP24A1 (converts 1,25D to calcitroic acid) can become uncoupled from the vitamin D receptor in the pancreas: too high in the tumor part and too low in the insulin-secreting part. So the tumor is protected from the anti-proliferative effect of 1,25D, while insulin secretion will rise with 25D concentration. PMID: 25090635

 

In the endocrine cells of PDAC [pancreatic ductal adenocarcinoma] patients, CYP24A1 expression was significantly lower than in the patients with CP (and probably in the normal pancreas), while it was increased in the tumor cells. We speculate that the tight regulation of 1,25(OH)₂D₃ levels, needed in these cells for a balanced vitamin D-dependent regulation of insulin secretion is lost. As a consequence, higher vitamin D levels in patients with low CYP24A1 levels in the endocrine cells would lead to enhanced insulin secretion. This could then promote growth of neighboring tumor cells in a paracrine manner. Additionally, in the tumor itself, the high CYP24A1 levels would catabolize 1,25(OH)₂D₃ immediately, impairing its anti-tumorigenic effects. Indeed, in PDAC patients CYP24A1 levels correlated significantly with Ki67 expression, suggesting that tumors overexpressing CYP24A1 are highly proliferative. This hypothesis might explain the positive associations observed in some studies between vitamin D and pancreatic cancer, however it needs further proof.

 

I also found a new U-curve: risk of left ventricular concentric remodeling. 30-37 ng/ml was optimal. PMID: 23061475 Fibroblast growth factor 23 (FGF23) could be part of the mechanism. Vitamin D increased FGF23 in PMID: 24990351 and PMID: 24960544. FGF23 is associated with increased risk of left ventricular concentric hypertrophy (PMID: 19524924) and cardiovascular mortality (PMID: 24922628). FGF23 causes left ventricular hypertrophy in mice. PMID: 21985788

[midas]

Just a stab in the dark here but I would have thought you would only notice anything if you were Vit D deficiant before taking it.

 

I take 5000 IU D3 almost daily as I dont get enough sun light, and I must say I do feel brighter within myself since I started about 10 months ago.

[kurdishfella]

vitamin d had the strongest effect out of anything 

Edited by kurdishfella, 18 July 2020 - 01:06 AM.

[experimenting]

vitamin d had the strongest effect out of anything

What effects did you get?