The Mystery of Vitamin D Decoded

Chemical Structure of Vitamin D

  • Vitamin D is  a fat soluble prohormone
  • It promotes healthy skin and strong bones.
  • Vitamin D is known to be crucial in the transport and absorption of Calcium.
  • Unlike other vitamins, vitamin D synthesizes in in the skin.
  • According to the Mayo clinic, “vitamin D refers to several different forms of this vitamin. Two forms are important in humans: vitamin D2, which is made by plants, and vitamin D3, which is made by human skin when exposed to sunlight.
  •  Vitamin D2, known as ergocalciferol and Vitamin D3,  recognized as cholecalciferol.
  • Scientists identify D2 as C27H44O and D3 as C28H44O, which subsequently is also their chemical formula.

Chemical Structure of Vitamin D2 and D3

As mentioned in the book,  Advanced Nutrition and Human Metabolism, “structurally, vitamin D is derived from a steroid and is considered to be a seco-steroid because one of its four rings is broken. Vitamin D contains three intact rings (A,C and D) with a break between carbon 9 and 10 in the B ring. ergocalciferol and cholecalciferol differ in the structure of their side chain, but not in their general metabolism or functions in the body.”

Vitamin D2 and D3  Biochemical Reactions

chem1

Figure 1

Structural relationship of vitamin D3 (cholecalciferol) and vitamin D2(ergocalciferol) with their respective provitamins, cholesterol, and a classic steroid hormone, cortisol. The two structural representations presented at the bottom for both vitamin D3 and vitamin D.2 are equivalent; these are simply different ways of drawing the same molecule. It is to be emphasized that vitamin D3 is the naturally occurring form of the vitamin; it is produced from 7-dehydrocholesterol, which is present in the skin, by the action of sunlight (see Figure 2). Vitamin D2 (which is equivalently potent to vitamin D3 in humans and many mammals, but not birds) is produced commercially by the irradiation of the plant sterol ergosterol with ultraviolet light. (Norman 2011)

chem2

 

Figure 2

Photochemical pathway of production of vitamin D3 (cholecalciferol) from 7-dehydrocholesterol. The starting point is the irradiation of a provitamin D, which contains the mandatoryD5,7-conjugated double bonds; in the skin this is 7-dehydrocholesterol. After absorption of a quantum of light from sunlight (UV-B), the activated molecule can return to the ground state and generate at least six distinct products. The four steroids that do not have a broken 9, 10-carbon bond (provitamin D, lumisterol, pyrocalciferol, and isopyrocalciferol) represent the four diastereomers with either an a- or b-orientation of the methyl group on carbon-10 and the hydrogen on carbon-9. The two secosteroid products, vitamin D3, previtamin D3, and tachysterol3 have differing positions of the three conjugated double bonds. In the skin, the principal product is previtamin D3, which then undergoes a 1,7-sigmatropic hydrogen transfer from C-19 to C-9, yielding the final vitamin D3: Vitamin D3 can be drawn as either a 6-s-trans representation or as 6-s-cis representation depending upon the state of rotation about the 6,7-single bond. The resulting vitamin D3, which is formed in the skin, is removed by binding to the plasma transport protein, the vitamin D-binding protein (DBP), present in the capillary bed of the dermis. The DBP-D3then enters the general circulatory system. (Norman 2011)

Dietary Requirements

  • The RDA for Vitamin D was published in 2010.
  • Ages 1-70: 600 IU=15 micrograms
  • *This includes infants, adolescents, adult men/women,  pregnant and lactating women
  • Ages 70+: 800IU=20 micrograms
  • 5-15 minute daily sun exposure is also highly advised
  • In the summer, fair skin individuals can generate 10,000-20,000 IU of vitamin D, in a matter of 15 to 30 minutes.
  • People with higher melanin content (aka darker skin), need more time to generate vitamin D. This is mainly due to melanin blocking some of the UVB (short wave) rays.

Dietary Sources of Vitamin D 

 

Dietary Sources of Vitamin D Include:

  • Fatty fish, such as salmon, tuna and herring
  • Cheese
  • Butter
  • Eggs
  • Whole grains
  • Some cereals
  • Fortified milk

Vitamin D Deficiency

  • Vitamin D Deficiency is widespread across the world. This encompasses, both developing and developed nations
  • Vitamin D deficiency is mostly assessed by looking at Serum 25-OH D  (25-hydroxi vitamin D) concentrations. Concentrations less than 15 to 30 nmol/L are considered levels of deficiency
  • Rickets is caused by vitamin D deficiency in children and infants.

dwe00215g01Rickets symptoms and side effects include:

  • Little to no bone mineralization
  • Epiphyseal cartilage continues to grow, leading to enlargement of wrists, ankles and knees.
  • Bending of upper leg bones
  • Curving of spine
  • Pelvic and thoracic bones can also undergo some deformities, such as  rachitic rosary, characterized by “Beadlike bumps present at the junction of the ribs with their cartilages” (Encyclopedia of Medicine)

Osteomalacia, a bone thinning disorder,  is caused by vitamin D deficiency in older children and adults.

Unmasking-Osteomalacia

Osteomalacia symptoms and side effects include:

  • Continuous bone demineralization, which leads to chronic pain
  • Bending of upper leg bones
  • Curving of spine
  • Weakness in proximal muscles and bone fragility
  • Muscle cramps, numbness or tingling
  • Abnormal heart rate (due to low calcium levels)

Toxicity

images

  • Vitamin D is one of the most common vitamins to cause toxicity
  • The tolerable upper limit (TUL) = 4,000 IU= 100 micrograms. This includes, both children and adults.
  • Concentrations higher than 500 nmol/L of serum 25-OH D are toxic
  • Hypercalcemia occurs when there is an excessive amount of calcium in the blood.
  • Calcinosis occurs when calcium deposits itself in soft tissues, including organs, such as kidneys, heart, lungs and blood vessels.

X-Ray Showing Calcium Build-up 

 F1.large

Hypercalcemia  and Calcinosis symptoms and side effects include:

  • Excessive phosphorus in the blood, also known as hyperphosphatemia
  • Weakness
  • Nausea
  • Headaches
  • Anorexia
  • Hypertension
  • Renal dysfunction/renal failure
  • Death

Digestion, Absorption and Storage

vitamin-D-metabolism

Vitamin D Pathway

  • Vitamin D does not require digestion
  • It is absorbed from the micelle by passive diffusion with aid from fat and bile sats
  • Most vitamin D is absorbed in distal small intestine
  • Chylomicrons are responsible for 40% of vitamin D blood transport
  • Cholecalciferol, D3, diffuses from the skin, enters the blood system and is metabolized to 25-OH D3 (25-hydroxi) in the liver.
  • Serum Calcium homeostasis – actions to increase serum calcium

Picture1

  • Calcitriol synthesis is stimulated in response to changes in serum calcium concentrations and the release of PTH.
  • Normal serum calcium 8.5 to 10.5 mg/dL(2.12–2.62 mmol/L)
  • Hypocalcemia <8.5 mg/dL)
  • Calcium homeostasis
  • Calcitriol & the intestine, kidney, and bone

Recent Research Findings

  • In the past decade there have been many suspicions that vitamin D could be linked to depression. However, little research was carried concerning this issue.
  •  in 2013, the Department of Psychiatry and Behavioural Neurosciences, at St. Josephs Hospital, published their findings.
  • Their goal was to determine the relationship between depression and vitamin D Deficiency within developed nations. (this is mainly due to the fact that depression is more prevalent in developed nations rather than developing countries).
  • Focus group consisted of 31,424 adults (18 years and older)
  • Population groups and studies involved four developed nations. These include: USA, Netherlands, UK and Canada 
  • Studies involved:
  1. One case-control study
  2. Ten cross-sectional studies
  3. Three cohort studies. 
  • Tools and Tests  involved:

  1. standardized psychiatric interview for the DSM diagnoses of depressive disorders or ICD diagnoses of a depressive episode of depression.
  2. A clinical diagnosis of depressive disorder or a depressive episode
  3. Lastly, a diagnosis of depression using an established cut-off point on a validated rating scale. In this case,  scores  ⩾16 on the Center for Epidemiological Studies  and ⩾8 on the Geriatric Depression Scale.
  • Lower vitamin D levels (SMD = 0.60, 95% CI 0.23-0.97) were found in people with depression compared with controls.
  •  An increased odds ratio of depression for the lowest v. highest vitamin D categories in the cross-sectional studies (OR = 1.31, 95% CI 1.0-1.71).
  • The cohort studies showed a significant increase in the hazard ratio of depression for the lowest v. highest vitamin D categories (HR = 2.21, 95% CI 1.40-3.49)…
  • In conclusion, the author states, “The importance of vitamin D to many brain processes including neuroplasticity suggests that it might have a role in psychiatric illness such as depression…Overall, the summary estimates of all analyses suggest a relationship between vitamin D and depression, and all but one were close to being statistically significant.” 

Vitamin D Mini Quizz

  1.  What are the two active forms of Vitamin D?
  2. How are ergocalciferol and cholecalciferol different? name one characteristic.
  3. Where is vitamin D absorbed and stored?
  4. What is the RDA for pregnant women?
  5. T/F UV rays are considered vitamin D
  6. T/F Rickets only happens in developing nations

Bibliography

  1. Anglin, Rebecca. Samaan, Zainab. Walter, Stephen. Mcdonald, Sarah. (2013). Vitamin D Deficiency and Depression in Adults. British Journal Psychology. Retrieved from: http://bjp.rcpsych.org/content/202/2/100.long
  2. Mayo Clinic Staff. (2014) Osteomalacia.  Mayo Clinic. Retrieved from: http://www.mayoclinic.org/diseases-conditions/osteomalacia/basics/definition/con-20029393
  3. Mayo Clinic Staff. (2014) Vitamin D. Mayo Clinic. Retrieved from: http://www.mayoclinic.org/drugs-supplements/vitamin-d/background/hrb-20060400
  4. No author. (2011). Vitamin D” Fact Sheet for Health Professionals. National Institute of Health. Retrieved from: http://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/#h2
  5. No author. (2013).Osteomalacia. Boneporosis Project. Retrieved from: http://www.boneporosis.com/osteomalacia.html
  6. No Author. (2014) Calcinosis. Harvard Health Publications: Health Central.   Retrieved from: http://www.healthcentral.com/encyclopedia/408/666.html
  7. Sareen, G., & Jack, S. (2013). Vitam D. Advanced Nutrition and Human Metabolism. Belmont, CA: Wadsworth, Cengage Learning .
  8. Norman, Anthony  (2011). Vitamin D Chemistry <http://vitamind.ucr.edu/about&gt;
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