Researchers also put forward the suggestion of whether free 25-hydroxy-vitamin D (25(OH)D), the standard biomarker for vitamin D status, offers a better assessment of vitamin D levels in the host.
The US team say, “Recommended levels based on studies of the musculoskeletal system may or may not be appropriate for other vitamin D impacted conditions”.
“These include immune function, cancer prevention, cardiovascular health, neurologic function. Only further investigation will settle these issues.”
In recent years there has been renewed interest in vitamin D and its possible benefits on overall health. The resurgence is also attributed to the rise of vitamin D deficiency in children and adults world-wide.
The Institute of Medicine states that people with less than 20 nanograms of vitamin D per millilitre of blood are deficient.
Meanwhile, The Endocrine Society sets a higher threshold of 30 nanograms with neither guideline is more definitive than the other at this time.
‘Current guidelines vary’
"Recommendations based on earlier studies using a number of different tests for vitamin D levels persist and, not surprisingly, current guidelines vary," said author Dr Sylvia Christakos, a professor at Rutgers New Jersey Medical School.
"For example, it is not clear that the most optimal levels for vitamin D are the same for Caucasians, blacks or Asians alike. More laboratories are now implementing improved tests and efforts are being made to standardise results from different laboratories."
The review gathers over 100 studies in drawing its conclusions, which highlights the need to gain consensus through improved tests for vitamin D levels that are currently available.
The general consensus agrees that vitamin D supplements work best when taken with calcium for rickets and bone loss that occurs with ageing.
However, studies did not show supplements to be beneficial as protection against fracture if the elderly person was already sufficient in the vitamin.
The researchers, from Rutgers University and the University of California, San Francisco, also note that more vitamin D supplementation is not better.
Previous studies have shown that very high doses of vitamin D (300,000-500,00 iu taken over a year) seem to increase fracture risk.
Vitamin D supplementation is shown to reduce overall mortality with some studies suggesting that vitamin D might be beneficial for immune function, cancer and cardiovascular health.
However, as Dr Christakos points out a consistent benefit of vitamin D supplementation has yet to be shown.
She notes though that most studies have not discriminated between participants who are vitamin D sufficient or deficient.
Future research directions
The paper also discusses future areas of research with the molecular mechanisms involved in the control of the expression of the vitamin D hydroxylases a main focus.
“Understanding the mechanisms involved is critical to understanding dysregulation of 1,25(OH)2D3 production that occurs for example in chronic kidney disease and with age related bone loss,” the review says.
“New targets of 1,25(OH)2D3 will be identified which will provide a better understanding of 1,25(OH)2D3 actions in different regions of the intestine as well as in multiple other target tissues.
“New data from RCTs based on better assays of 25(OH)D3 will result in less variability and a gain in consensus for optimal vitamin D levels in different groups,” add the researchers.
The review goes on to describe the need for further large scale clinical trials that discriminate between participants with sufficient and insufficient vitamin D levels.
This is in order to better determine the suggested impact of vitamin D on immune function, cancer prevention and other diseases.
“These future studies will result in a new dimension in our understanding of the impact of the vitamin D endocrine system on skeletal health and on extra skeletal biological responses.”
Published online: doi.org/10.1016/j.metabol.2019.06.010
“New developments in our understanding of vitamin D metabolism, action and treatment.”
Authors: Sylvia Christakos et al.