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Background: Vitamin D (calciferol) is a group of fat-soluble compounds, which are essential for calcium homeostasis, immunomodulation, antiproliferative effects, and more. It can also be viewed as a prohormone. Almost every cell in the human body has a receptor for vitamin D. Its synthesis depends on multiple factors. Review results: Vitamin D deficiency affects almost 50% of the world’spopulation, making it the most common vitamin deficit. There are multiple causes, mostly related to the modern lifestyle and ineffective exposition to the sun. The modern diet also lacks good sources of the vitamin, which makes supplementation the best option for optimal health. Supplements should be administered after serum level tests. Measurements below 20 ng/ml (50 nmol/l) are indication for supplementation. How effective the supplementation is will depend on the type of supplement, individual’s genetic factors, and with what foods the supplement is taken with. Dietary reference values for adequate intake and tolerable upper limit should be taken into consideration as well. Serum levels above 30 ng/ml (above 70 nmol/l) are considered optimal for health. There is a risk of toxicity in cases of over-supplementation and serum levels above 150 ng/ml (375 nmol/l). Conclusion: The widespread vitamin D deficiency leads to many public health risks. Supplementation can have a therapeutic effect in many different conditions. To maximize the effect, and reduce the risks of toxicity, an individual assessment of the most appropriate regimen and the dosage of vitamin D supplementation is needed.
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3554 https://www.journal-imab-bg.org J of IMAB. 2021 Jan-Mar;27(1)
Literature review
SUPPLEMENTATION WITH VITAMIN D - CURRENT
RECOMMENDATIONS
Dimitar B. Marinov, Darina N. Hristova
Department of Hygiene and Epidemiology, Faculty of Public Health, Medical
University of Varna, Bulgaria.
Journal of IMAB - Annual Proceeding (Scientific Papers). 2021 Jan-Mar;27(1)
Journal of IMAB
ISSN: 1312-773X
https://www.journal-imab-bg.org
ABSTRACT
Background: Vitamin D (calciferol) is a group of fat-
soluble compounds, which are essential for calcium
homeostasis, immunomodulation, antiproliferative effects,
and more. It can also be viewed as a prohormone. Almost
every cell in the human body has a receptor for vitamin D.
Its synthesis depends on multiple factors.
Review results: Vitamin D deficiency affects almost
50% of the world’s population, making it the most com-
mon vitamin deficit. There are multiple causes, mostly re-
lated to the modern lifestyle and ineffective exposition to
the sun. The modern diet also lacks good sources of the
vitamin, which makes supplementation the best option for
optimal health. Supplements should be administered after
serum level tests. Measurements below 20 ng/ml (50 nmol/
l) are indication for supplementation. How effective the
supplementation is will depend on the type of supplement,
individual’s genetic factors, and with what foods the sup-
plement is taken with. Dietary reference values for adequate
intake and tolerable upper limit should be taken into con-
sideration as well. Serum levels above 30 ng/ml (above 70
nmol/l) are considered optimal for health. There is a risk
of toxicity in cases of over-supplementation and serum lev-
els above 150 ng/ml (375 nmol/l).
Conclusion: The widespread vitamin D deficiency
leads to many public health risks. Supplementation can
have a therapeutic effect in many different conditions. To
maximize the effect, and reduce the risks of toxicity, an in-
dividual assessment of the most appropriate regimen and
the dosage of vitamin D supplementation is needed.
Keywords: vitamin D, supplementation, recommen-
dations, safety, toxicity,
BACKGROUND
Vitamin D (calciferol) is a group of fat-soluble com-
pounds, which are essential for the maintenance of the min-
eral balance inside the organism. The biological effects of
vitamin D include the mediation of calcium homeostasis,
immunomodulation, antiproliferative effects, and more [1].
Science has found out that almost every cell in the
human body has a receptor for vitamin D (VDR) [2]. Given
the pleiotropic effects of vitamin D, it can be viewed as a
prohormone.
In nature, vitamin D exists in two different forms.
The first one is vitamin D2 (ergocalciferol), which is pro-
duced by phytoplankton, yeast, and fungus under the ef-
fect of UV rays. Vertebrate animals, including humans, can-
not produce vitamin D2, but the second one – vitamin D3
(cholecalciferol). It is synthesized in the stratum basale and
stratum spinosum in the skin from 7-dehydrocholesterol
when there is sufficient exposure to direct sunlight. Syn-
thesis depends on the intensity of UV-B rays, atmospheric
air pollution, season, geographic latitude and longitude,
ozone layer thickness, cloudiness, time spent outside,
clothing, sunscreen usage, skin color, and age [3]. Evidence
suggests that skin aging reduces its capacity for vitamin D
synthesis even during optimal sun exposure.
REVIEW RESULTS
Vitamin D deficiency affects almost 50% of the
world’s population [4]. This is the most common vitamin
deficit. Scientists are calling it a pandemic [5]. It affects
people of every age, gender, race, and region [6]. The causes
for this are many but usually related to too short or inef-
fective exposition to the sun. Not spending enough time
outside is a typical lifestyle for the modern person and con-
tributes to the pandemic of vitamin D deficiencies.
Scientific evidence suggests that Vitamin D defi-
ciency is related to many illnesses and pathological con-
ditions [7]:
1. Rickets, osteoporosis, adolescent idiopathic sco-
liosis [8]
2. Cardiovascular conditions – endothelial disfunc-
tion, vascular calcification, arterial hypertension, dysli-
pidemia [9]
3. Autoimmune diseases and infections [10, 11]
4. Metabolic diseases (obesity, type 2 diabetes) [12].
Patients with optimal vitamin D levels have better control
over their body fat compared to deficient ones [13]
5. Neoplasia (breast, pancreas, colon, ovarian and
testicular cancers) [1]
6. Neurological conditions (depression, dementia,
schizophrenia, multiple sclerosis, Parkinson’s) [14, 15]
7. Reproductive problems and pathological preg-
nancy [16, 17]
There is also an association between vitamin D and
physical performance [18]. Optimal levels boost speed and
strength in athletes.
The modern diet often lacks popular nutritional
sources of Vitamin D, such as oily fish and egg yolks [19].
The high incidence of human deficiency makes supplemen-
https://doi.org/10.5272/jimab.2021271.3554
J of IMAB. 2021 Jan-Mar;27(1) https://www.journal-imab-bg.org 3555
tation the best option for improving health status.
The protective effect of vitamin D is manifested at
blood levels above 30 ng/ml (above 70 nmol/l). Lower lev-
els and especially below 20 ng/ml (50 nmol / l) is a defi-
ciency indicator, and the use of therapeutic supplements
are highly recommended [20].
The daily dosage of vitamin D supplements
The dosage regimen for vitamin D supplements de-
pends on many factors: the severity of the deficiency, the
type of vitamin supplement (D2 or D3), patient conven-
ience, body weight (obese patients need higher doses than
normal-weight patients due to extra fat), risk of overdose,
etc. Also relevant is the genotype - in recent years, a
number of polymorphism-related genes have been identi-
fied in VDR receptors and enzymes involved in the syn-
thesis, hydroxylation, and transport of 25-hydroxyvitamin
D (7-dehydrocholesterol reductase (DHCR7), polypeptide
1 (CYP2R1), etc.). Polymorphisms influence the response
to a vitamin D supplement.
Ideally, supplements are administered after labora-
tory tests of serum vitamin D3 levels [21]. Measuring val-
ues below 20 ng/ml (50 nmol/l), especially in the high-
risk population groups, is an indication for vitamin D sup-
plementation. It is recommended that vitamin D3 supple-
ments should be used for significantly better bioavai-
lability. Because vitamin D is a fat-soluble nutrient, it is
important that the patients are properly instructed to take
the supplement after meals or with fatty foods, preferably
during the largest meal [22]. This ensures an optimal re-
lease of bile and pancreatic enzymes required for the ab-
sorption of vitamin D. Many medications and supplements
reduce the absorption of vitamin D. Vitamin D supplements
should not be taken during the same meal with statins,
anticonvulsants, corticosteroids, and fiber-rich supple-
ments.
When dosing with the supplement, it is important
to take into account dietary reference values (DRVs) for
Adequate Intake (AI) and Upper Tolerable Limit (UL) [23,
24].
There are different regimens for taking supple-
ments: daily dose or bolus (weekly or monthly). Choices
are made individually, according to the severity of the
deficit, the capabilities (including Intellectual) and the
convenience of the individual. In bolus, the monthly dose
can reach up to 50,000 IU. Evidence suggests that it may
be more beneficial to take the supplement every day, thus
providing a stable concentration of circulating vitamin
D. Daily intake (rather than bolus) is advisable for endo-
crine and autoimmune diseases and for the prevention of
respiratory infections.
Too high dosage supplementation, especially in the
bolus regimen, carries the risk of toxic action. It is rec-
ommended to monitor the levels of vitamin D in blood
with laboratory test: before supplementation and at every
6-month period. Levels of 25(OH)D in serum above 150
ng/ml (375 nmol/l) are potentially toxic [25]. There is an
increased risk of toxicity in cases of:
• intake of more than 10,000 IU / day for 3 months
or more
• intake of more than 300,000 IU per 24-hour pe-
riod
CONCLUSION:
The widespread vitamin D deficiency leads to many
public health risks. Supplementation can have a therapeu-
tic effect in many different conditions. To maximize the
effect, and reduce the risks of toxicity, an individual as-
sessment of the most appropriate regimen and the dosage
of vitamin D supplementation is needed.
Fig. 1. Dietary reference values (DRVs) for Adequate Intake (AI) and Upper Tolerable Limit (UL) for vit. D sup-
plementation.
Adequate Intake (AI)
Infants aged 7-12 months 10mkg 400 IU/day
1-75 years of age, pregnancy, and lactation 15mkg 600 IU/day
Over the age of 75 20mkg 800 IU/day
Upper Tolerable Limit (UL)
Infants aged 0-12 months 25mkg 1000 IU/day
1-10 years of age 50mkg 2000 IU/day
Over the age of 10, pregnancy and lactation 100mkg 4000 IU/day
3556 https://www.journal-imab-bg.org J of IMAB. 2021 Jan-Mar;27(1)
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Address for correspondence
Dimitar Borisov Marinov,
Medical University - Varna; 55 Marin Drinov Str., Varna, Bulgaria
E-mail: mitak_1992@abv.bg
Please cite this article as: Marinov DB, Hristova DN. Supplementation with vitamin D - current recommendations. J of
IMAB. 2021 Jan-Mar;27(1):3554-3556. DOI: https://doi.org/10.5272/jimab.2021271.3554
Received: 12/11/2019; Published online: 25/01/2021
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