Why many vitamin D trials fail to find benefits - Nov 2016

.1) Trials rarely allow modifying the dose size - so as to compensate for
  obesity
   age (weight of child)
   health problems - especially those that consume Vitamin D
   pre-existing deficiency
   gut problems
   no gallbladder
   use of drugs such as statins
   smoking etc

2) Trials often do not last long enough
  About 1/3 of the trials which I read would have had a benefit if they had only lasted longer
  but to minimize trial costs trials are kept short

3) Trials essentially must be monotherapy -no cofactors such as Magnesium permitted
  Meta-analyses never consider trials with co-factors, so if a researcher wants his data to be used he does not use cofactors   1

4) Many trials use too small a dose to possibly make a difference
  Have seen many trials just using 1,000 IU
  One trial used just 200 IU - and did not find a difference!!
  Imagine a trial using 1/20 a dose of Aspirin - it would be very unlikely to find any benefit

5) RCTs typically require a placebo group, but many researchers now find it unethical to not give vitamin D to all participants
  so their trial is not an RCT - note that an increasing Percentage of the Vitamin D proofs are not RCT

6) Some RCTs are now terminated because
   Researchers found too much pain/suffering in those getting the placebo (unethical to give placebo)
     1, 2, 3,
   Too many participants getting the placebo dropped out as they noticed the other group feeling much better and having fewer health problems

7) Some countries (about 30%) consider a mere 20 nanograms to be sufficient
   When they compare those with < 20 nanograms to those with > 20 nanograms they do not see any benefit
   Occasionally they include charts of the data - in which the benefits of vitamin D can be seen at 30 or 40 nanograms

8) RCTs ignore gene differences that reduce Vitamin D getting to the cells
   There is at least a 3 times increased risk for 12 diseases for people having just a Vitamin D Receptor problem
   Note: There are 5 additional important Vitamin D genes

9) RCTs sometimes use long times between doses
   > 3-week dosing interval provides less benefit
   > 6-month dosing intervals can result in problems (negative benefits)

10) RCT researchers are occasionally rewarded for NOT finding a benefit
   Example; Professor who concluded that vitamin D (800 IU) does not help bones got 324,000 dollar prize- Nov 2015

11) RCTs rarely use loading doses to restore vitamin D levels in a week or so
   Without loading doses many people will fail to show a benefit/get repleted within the typical short RCT length

12) Some RCTs mistakenly continue to use Vitamin D2
   D2 is significantly less effective the D3 - especially for non-daily doses
   Sometimes D2 actually reduces the level of D3
   Over a decade ago Vets decided that Vitamin D2 should not be used on ANY mammal
     guess we have to remind doctors that humans are mammals too
13) Some RCT's give Vitamin D when many participants already have enough

14) All participants were allowed to take some vitamin D
   Many elderly now take 800 IU of vitamin D - which is 40% of 2,000 IU

15) RCT was given in an area with low Magnesium in water
  Too little Magnesium in groundwater
  Too much Magnesium and Calcium in groundwater - so water is deharded by provider or by household
  Water is desalinated (17,000 desalination plants, 5% of all water consumed)
  Water was passed thru a de-osmosis filter

16) Some people decided to not participate in trial because of a health problem
  RCT particiants probably are healthier than general population
    still have gallbladder, not have gut problems, have higher vitamin D levels, etc.

17) Trial used too low of a Vitamin D threshold (typically 30 ng)
  up to 150 ng may be needed
     Will notice little benefit if a disease needs 50 ng, but trial had a goal of only 30 ng

18) Trial used vitamin D measurements from a variety of testers

See also VitaminDWiki

• Vitamin D Random Controlled Trials are becoming impossible
• More than 16 reasons why Vitamin D trials fail – Oct 2020
• Vitamin D and RCTs (Randomized Controlled Trials)
• Intervention - Vitamin D has 824 studies - more than half of which are NOT RCT
• Several more Vitamin D analyses fail to consider dose size, duration, etc. – Dec 2013
• Is it ethical to NOT give vitamin D in osteoporosis trials– NEJM Sept 2010 many years ago!
• National Osteoporosis Society of UK declares that 12 ng of vitamin D is enough – June 2013
  • Example of the many ways that researchers are rewarded for showing that (a tiny amount) of vitamin D does not provide a benefit
• Clinical Trials of vitamin D can have “biological flaws” – Jan 2015
  • Even if many RCT show benefits AND many subsequent meta-analyses conclude that there is a benefit the doctors often ignore them
  • Example: Colorectal cancer 40 percent less likely if 1000 IU more Vitamin D – 21st meta-analysis – Oct 2021
  • Example: Vitamin D and fractures – 24 meta-analyses and counting – Dec 2014