Effect Of High-Dose Vitamin D Supplementation On Volumetric Bone Density And Bone Strength

[Mito]

Key Points

Question Does higher-dose vitamin D supplementation improve bone mineral density (BMD, measured using high-resolution peripheral quantitative computed tomography) and bone strength (measured as failure load)?

Findings In this randomized clinical trial that included 311 healthy adults, treatment with vitamin D for 3 years at a dose of 4000 IU per day or 10 000 IU per day, compared with 400 IU per day, resulted in statistically significant lower radial BMD (calcium hydroxyapatite; −3.9 mg HA/cm3 and −7.5 mg HA/cm3, respectively); tibial BMD was significantly lower only with the daily dose of 10 000 IU. There were no significant differences in bone strength at either the radius or tibia.

Meaning Among healthy adults, supplementation with higher doses of vitamin D did not result in improved bone health; further research would be needed to determine whether it is harmful.

Abstract
Importance Few studies have assessed the effects of daily vitamin D doses at or above the tolerable upper intake level for 12 months or greater, yet 3% of US adults report vitamin D intakes of at least 4000 IU per day.

Objective To assess the dose-dependent effect of vitamin D supplementation on volumetric bone mineral density (BMD) and strength.

Design, Setting, and Participants Three-year, double-blind, randomized clinical trial conducted in a single center in Calgary, Canada, from August 2013 to December 2017, including 311 community-dwelling healthy adults without osteoporosis, aged 55 to 70 years, with baseline levels of 25-hydroxyvitamin D (25[OH]D) of 30 to 125 nmol/L.

Interventions Daily doses of vitamin D3 for 3 years at 400 IU (n = 109), 4000 IU (n = 100), or 10 000 IU (n = 102). Calcium supplementation was provided to participants with dietary intake of less than 1200 mg per day.

Main Outcomes and Measures Co-primary outcomes were total volumetric BMD at radius and tibia, assessed with high resolution peripheral quantitative computed tomography, and bone strength (failure load) at radius and tibia estimated by finite element analysis.

Results Of 311 participants who were randomized (53% men; mean [SD] age, 62.2 [4.2] years), 287 (92%) completed the study. Baseline, 3-month, and 3-year levels of 25(OH)D were 76.3, 76.7, and 77.4 nmol/L for the 400-IU group; 81.3, 115.3, and 132.2 for the 4000-IU group; and 78.4, 188.0, and 144.4 for the 10 000-IU group. There were significant group × time interactions for volumetric BMD. At trial end, radial volumetric BMD was lower for the 4000 IU group (−3.9 mg HA/cm3 [95% CI, −6.5 to −1.3]) and 10 000 IU group (−7.5 mg HA/cm3 [95% CI, −10.1 to −5.0]) compared with the 400 IU group with mean percent change in volumetric BMD of −1.2% (400 IU group), −2.4% (4000 IU group), and −3.5% (10 000 IU group). Tibial volumetric BMD differences from the 400 IU group were −1.8 mg HA/cm3 (95% CI, −3.7 to 0.1) in the 4000 IU group and −4.1 mg HA/cm3 in the 10 000 IU group (95% CI, −6.0 to −2.2), with mean percent change values of −0.4% (400 IU), −1.0% (4000 IU), and −1.7% (10 000 IU). There were no significant differences for changes in failure load (radius, P = .06; tibia, P = .12).

Conclusions and Relevance Among healthy adults, treatment with vitamin D for 3 years at a dose of 4000 IU per day or 10 000 IU per day, compared with 400 IU per day, resulted in statistically significant lower radial BMD; tibial BMD was significantly lower only with the 10 000 IU per day dose. There were no significant differences in bone strength at either the radius or tibia. These findings do not support a benefit of high-dose vitamin D supplementation for bone health; further research would be needed to determine whether it is harmful.

Effect of High-Dose Vitamin D Supplementation on Volumetric Bone Density and Bone Strength

 

[Progesterone]

well sh*t

 

[shepherdgirl]

"Sunlight exposure for ≥5 h a day was significantly associated with a decreased OR (odds ratio) of fracture in older Korean adults with osteoporosis. This association was also significant in patients with vitamin D insufficiency."
From:

Association between Daily Sunlight Exposure and Fractures in Older Korean Adults with Osteoporosis: A Nationwide Population-Based Cross-Sectional Study​

Hye Jun Lee,1 Choon Ok Kim,

2 and Duk Chul Lee

1

Association between Daily Sunlight Exposure and Fractures in Older Korean Adults with Osteoporosis: A Nationwide Population-Based Cross-Sectional Study

We aimed to investigate the association between daily sunlight exposure duration and fractures in older Korean adults with osteoporosis.We utilized data from the 2008–2011 Korea National Health and Nutrition Examination Survey. Osteoporosis was ...

www.ncbi.nlm.nih.gov

 

[LucH]

Conclusions and Relevance Among healthy adults, treatment with vitamin D for 3 years at a dose of 4000 IU per day or 10 000 IU per day, compared with 400 IU per day, resulted in statistically significant lower radial BMD; tibial BMD was significantly lower only with the 10 000 IU per day dose. There were no significant differences in bone strength at either the radius or tibia. These findings do not support a benefit of high-dose vitamin D supplementation for bone health; further research would be needed to determine whether it is harmful.

There is a bias in this study. If you take more than 400 - 2000 IU of vitamin D3 supplement, you need vitamin K2 to make calcium accessible, whether this calcium comes from bone remodeling (Via PTH) or from a supplement. And if this supplement exceeds 250 mg of Ca, it is very likely that this Ca will be deposited where it is not needed, i.e. in the soft tissues of the joints or in the arteries (combined with fibrin).
=> interaction between vit A (retinol), K2 and D3. If a study doesn't include these parameters, it's no use.
Moreover, vitamin D is impacted by Mg status (round 400 - 450 mg Mg) by people who have difficulties to go above 35 ng/ml.
Vitamin D and magnesium work in a close correlation: without magnesium, vitamin D cannot be transformed into its active form, a relationship that is often overlooked.
80 % of people are deficient in Mg.
Magnesium is a directly primordial substance for three eminently important points (1):
1. Vitamin D enzymes. The enzymes responsible for transforming vitamin D into these different forms are totally dependent on magnesium.
2. Transport molecules. Vitamin D transport molecules in the body also need magnesium.
3. Regulation of vitamin D. PTH, a hormone formed in the parathyroid glands and regulating the metabolism of vitamin D, is strongly influenced by magnesium.
Sources:
1) Zofková I , Kancheva RL. The relationship between magnesium and calciotropic hormones. Magnesium Research : Official Organ of the International Society for the Development of Research on Magnesium [1995, 8(1):77-84]
2) Medalle R, Waterhouse C, Hahn TJ. Vitamin D resistance in magnesium deficiency. Am J Clin Nutr. 1976 Aug;29(8):854-8.
=> Four patients with gastrointestinal disorders, and one patient with chronic alcoholism presented with both hypocalcemia and hypomagnesemia. Pharmacological doses of either ergocalciferol (D2) or dihydrotachysterol (DHT) did not correct the hypocalcemia except in one patient who had a minimal rise in serum calcium. (DHT is a synthetic vitamin D analog activated in the liver that does not require renal hydroxylation like vitamin D 2). Magnesium repletion simultaneously corrected the hypomagnesemia and hypocalcemia.

Factors that facilitate the absorption of vitamin D3
But if you take a vitamin D3 supplement and you are below 35 ng/ml, what are the protective/facilitative factors or those that counteract absorption?
- A magnesium intake that is neither too high nor too low (RDA Mg: 360 and 420 mg depending on gender F/M) is favorable. An excess of Mg will counteract the absorption of vitamin D3. (11)
- Membrane protection with 20 IU of vitamin E (at least a mixture of 2 tocopherols, alpha and gamma). (Cfr Chris Masterjohn for the dosage). Vitamin E and beta-carotene protect membranes from oxidation.
- Quality cholesterol: Cholesterol plays a protective role in weakened membranes. (12) You will pump out all the vitamin E if the membranes are weakened, and you will then have excess ox-LDL (oxidized LDL), and inflammation.
- An excess of polyunsaturated fatty acidsTo make matters worse, if you ingest a lot of omega-6, oils and nuts rich in PUFA, you will suck out a good part of the vitamin D if your ratio is HS.
If the MUFA:PUFA ratio > 1, you will have difficulty increasing 25(OH)D levels. Which brings us directly to the 18-20g and 12-15g of PUFA consumed daily by American men and women (Kris-Etherton, 2000) and their negative impact on the absorption of the already low amounts of vitamin D in the food.
Monounsaturated fatty acids facilitate the absorption of vitamin D (olive, avocado, macadamia, for example). Saturated fatty acids (SFA) are probably neutral at this level. But given that these SFAs contribute to the stability of the membranes, care should be taken to have a 50/50 ratio between SFAs and MUFAs. And as little PUFA as is necessary for metabolism (1% = 22 gr. This is already calculated broadly. 4% is the level not to be crossed. 6% is harmful). (13)
Decoding: If you store unnecessary PUFAs/not essential for metabolism, you will increase the fragility of the membranes (oxidation and inflammation). At the end of the race, you will divert a fraction of the stock of vitamin E and vitamin D to reduce inflammation... You will therefore have to try to get out of this impasse, in particular by modulating with the parameters above.
PS: This is only a summary. I'm not allowed to post a link (censored). Make a Google search with:
"Absorption de la vitamine D insuffisante ?" and Chez Mirzoune et Ciboulette if you want more details and sources. (translator needed).

 

[revenant]

"If the MUFA:PUFA ratio > 1, you will have difficulty increasing 25(OH)D levels. "

How does this make sense... would you want a lower than 1 ratio then, i.e. eating more PUFA than MUFA?

"care should be taken to have a 50/50 ratio between SFAs and MUFAs"

So mostly PUFA and equal amounts of SFA and MUFA is what you're saying, which can't be right... right?

 

[LucH]

If the MUFA:PUFA ratio > 1, you will have difficulty increasing 25(OH)D levels. "

No, it's a transcription error on my part. You must read: If the PUFA / MUFA ratio > 1, you will have difficulties to increase 25(OH)D levels.
It is obvious that the overall intake of PUFA must be very limited, and only from non-manufactured foods. A contribution in correlation with the "needs" of the body. Needs which are very moderate, as you know (4 to 6 g in my opinion, not necessarily every day), provided that this intake is always associated with an SFA intake (and some vitamin E; 20 UI is enough).

"care should be taken to have a 50/50 ratio between SFAs and MUFAs"

This means we must always bring more SFA than MUFA, with a maximum intake of MUFA equal to 50% of SFA.
Explained more simply: MUFA / SFA => 50/50.

NB: As you know, we can do without omega-6 if we have a supply of vitamin B6. But we are surrounded by the ALA. We must be realistic and take the context into account. This last remark is counterproductive. Not a good idea to dwell on the subject here. Read between the lines...