Vitamin D: The Sunshine Vitamin

I remember there was this one time, during a dinner at my in-law's home, many years ago, when I stood listening as my father-in-law said: “If science could cure one thing, rickets should be the first.”  

A stark, confused silence filled the room as everyone within hearing range attempted to gauge whether or not he was being serious (he is a rather serious kind of man). 

Though in our blink of confusion, not one amongst us was willing to give voice to the words we were all thinking (or more precisely, the tone in which they were being thought), although they must have read plainly on our expressions in variations of: ‘Uh, they have already, Phil, it’s called fortified milk.’

Still, one must be respectful, yes? After all, it isn't always what people say so much as what motivated them to say it. Maybe rickets was a serious problem for lads growing up in post-war Guildford; and maybe he was left scarred by some childhood memory; or maybe, in his profound insight, he had glimpsed the forthcoming (now present) age of dietary intolerance and SPF 15. It wouldn’t surprise me, he is a rather insightful kind of man.

Without ever giving much thought as to why, I have always taken cod liver oil pills. My mom told me they were good for me and I believed her. 

Mind you, she also enjoyed puncturing open the capsules in her mouth and savoring the yummy cod liver oil flavor, which should have made me a little suspicious of her sound judgement.

What I have since learned (since, as in this past week) is that when it comes to vitamin D (or any vitamin for that matter) it is important to remember that it is intended to act as a dietary supplement; as in, only take as required, and preferably with your physician’s prior knowledge.

And to never blindly accept translucent amber pills from someone who actually enjoys the taste of cod liver oil, even if she is your mom. 

Vitamin D3

VITAMIN D is the name given to a group of fat-soluble prohormones. [63][11]

The most important compounds in this group are vitamin D3 and vitamin D2. [12]

Both of which are converted to 25-hydroxyvitamin D (calcidiol) in the liver, and then further modified in the kidneys to 1,25-dihydroxyvitamin D (calcitriol).

Calcitriol, the biologically active form of vitamin D [13] circulates as a hormone in the blood, regulating the concentration of calcium and phosphate in the bloodstream and promoting the healthy growth of bone. Calcitriol also affects neuromuscular and immune function. [14]

Vitamin D production is greatest in two innermost strata of the 

epidermis, the stratum basale and the stratum spinosum.

Vitamin D3 is produced photochemically within our skin when exposed to sunlight (specifically UVB radiation). [2][58][63][11]

Adequate amounts of vitamin D can be produced with moderate sun exposure to the face, arms and legs, averaging 5–30 minutes twice per week without sunscreen. [59][60][31]

Sunscreen with an SPF of 15 based on the UVB spectrum has been reported to decrease vitamin D synthetic capacity by 98%. [62] (SVP do NOT take this to mean you should stop wearing sunscreen in general!)

DIETARY SOURCES OF VITAMIN D INCLUDE:

• Fortified foodstuffs, such as: dairy, juices and cereals;

• Shiitake Mushrooms, Portobello Mushrooms, and alfalfa shoot;  [3,4]

• Cod liver oil, oily fish (eg: salmon, mackerel, tuna, sardines, trout) eggs, and beef liver. [3]

• In terms of cooking, vitamin D is not entirely heat stable. [6]

Source: webmd.com

The Institute of Medicine (IOM) has developed the following recommended daily allowances (RDA) of vitamin D, assuming minimal sun exposure: [63, 75-76]

VITAMIN D DEFICIENCY

• Vitamin D levels are determined by a blood test called a serum 25-hydroxyvitamin D blood test. [18-20][63]

• A normal level is 20-50 ng/mL, deficiency is considered anything less than 20 ng/mL, and a vitamin D level greater than 50 ng/mL is considered high.

• Getting tested for vitamin D deficiency makes sense if you have osteoporosis, or a disorder such as kidney disease that affects your ability to make the active form of vitamin D, or intestinal malabsorption caused by medications or conditions such as celiac disease. [79] (This is not a comprehensive list, but you get the idea.)

• A diet deficient in vitamin D in conjunction is known to cause rickets in children and osteomalacia in adults. [21][22]

• Rickets can be caused by calcium or phosphorus deficiency, as well as (though not solely due to) a lack of vitamin D. [24][25]  

• It is characterized by bowing of the legs due to softening of the bones. [23]

• Today, it is largely found in developing countries, [26] in children with genetic disorders such as pseudo-vitamin D deficiency rickets, [27] as well as within some Aboriginal populations.

• Hedy Fry, a physician and the former head of the British Columbia Medical Association, points to an increase in the cases of rickets among Aboriginal children, with a rate four to five times higher than the national average, and says the dietary shift away from cold-water fish—which is rich in vitamin D—to a more typical Western diet is the cause. [5]

• Osteomalacia is a disease which reduces calcium absorption and increases calcium loss from bone in adults. 

• It is characterized by softening of the bones, leading to bending of the spine, bowing of the legs, proximal muscle weakness, bone fragility, and increased risk for fractures. [28]

• Osteomalacia is usually present when 25-hydroxyvitamin D levels are less than about 10 ng/mL. [12] 

The role of vitamin D in Ca2+ regulation is shown in orange.

VITAMIN D TOXICITY

• Hypervitaminosis D, (vitamin D toxicity) is rare. [31][40-42]

• In healthy adults, sustained intake of more than 1250 μg/day (50,000 IU) can produce overt toxicity after several months and can increase serum 25-hydroxyvitamin D levels to 150 ng/ml and greater. [31][32]

• Those with certain medical conditions, such as primary hyperparathyroidism, [33] (overactivity of the parathyroid glands which control the bodies' Ca2+ levels [29]) are far more sensitive to vitamin D and develop hypercalcemia (elevated Ca2+ level in the blood [30]) in response to any increase in vitamin D nutrition.

• If hypercalcemia is not treated, it results in excess deposits of calcium in soft tissues and organs such as the kidneys, liver, and heart, resulting in pain and organ damage. [31][34][35]

•  In this randomized, placebo controlled trial,163 women (aged 57 to 90) took calcium citrate tablets to meet their recommended intake of 1,200 mg/day. They also took various doses of vitamin D, ranging from 400 to 4,800 IU/day.

• About 9% of participants developed hypercalcemia, and 31% developed excess levels of calcium in their urine (hypercalciuria). [57][58]

• Maternal hypercalcemia during pregnancy may increase fetal sensitivity to effects of vitamin D and lead to a syndrome of mental retardation and facial deformities. [36][37]

• Exposure to sunlight for extended periods of time does not normally cause vitamin D toxicity. The concentrations of vitamin D precursors produced in the skin reach an equilibrium, and any further vitamin D produced is degraded. [33]

THE RESEARCH

Dietary Fat Increases Vitamin D-3 Absorption

Dawson-Hughes et al (2014) found that, 

"The presence of fat in a meal with which a vitamin D-3 supplement is taken significantly enhances absorption of the supplement." [9][10]

Vitamin D and childhood obesity

• In this 2010 study, researchers tracked the vitamin D levels, BMI, waist circumference and subscapular-to-triceps skin fold ratio in school children, aged 5-12 over a period of 2.5 years and found low levels of vitamin D to be a likely risk factor in childhood obesity. [8]

Cardiovascular Disease

• According to the findings of this meta-analysis of existing randomized controlled trials, the taking of vitamin D supplements with or without calcium may reduce the risk of stroke, cerebrovascular disease, cardial infarction, or ischaemic heart disease by no more than 15%. [43] 
• Supplementation has no effect on blood pressure. [44] 

Cognition and Dementia [45][46]

• In this 2014 study, researchers found that participants who were severely vitamin D deficient were more than twice as likely to develop dementia and Alzheimer's disease.

• The study looked at 1,658 adults aged 65 and over, who were able to walk unaided and were free from dementia, cardiovascular disease and stroke at the start of the study. The participants were then followed for six years to investigate who went on to develop Alzheimer's disease and other forms of dementia.

"Clinical trials are now needed to establish whether eating foods such as oily fish or taking vitamin D supplements can delay or even prevent the onset of Alzheimer's disease and dementia. We need to be cautious at this early stage and our latest results do not demonstrate that low vitamin D levels cause dementia.”

• The study also found evidence to confirm that vitamin D levels above 50 nmol/L are most strongly associated with good brain health.

Infectious Disease

• Low levels of Vitamin D have been associated with an increased risk of both viral (HIV and Influenza) and bacterial infections (TB). This is believed to be because of the role vitaminD3 plays in autophagy. [47-50][79]

Pregnancy

• Low levels of vitamin D in pregnancy are associated with gestational diabetes, pre-eclampsia, and "small for gestational age infants." [51] 

Cancer

"Early epidemiologic research showed that incidence and death rates for certain cancers were lower among individuals living in southern latitudes, where levels of sunlight exposure are relatively high, than among those living at northern latitudes. 

Because exposure to ultraviolet light from sunlight leads to the production of vitamin D, researchers hypothesized that variation in vitamin D levels might account for this association." [63]

• In studies of cancer cells and of tumors in mice, vitamin D has been found to have several activities that might slow or prevent the development of cancer, including promoting cellular differentiation, decreasing cancer cell growth, stimulating cell death (apoptosis), and reducing tumor blood vessel formation (angiogenesis) [63-67]

• The Harvard Public Health Review goes on record as saying, 

"Certain cancers and immune dysfunctions are strongly associated with vitamin D deficiency." [5]

• In this 2010 study, researchers found that patients with insufficient vitamin D levels at the time of being diagnosed with chronic lymphocytic leukemia were 66% more likely to suffer worsening condition and require chemotherapy when re-assessed for the study 3 three years later. [7]

• Numerous epidemiologic studies have shown that higher intake or blood levels of vitamin D are associated with a reduced risk of colorectal cancer. [63] [68-71]

But not all ...

• The Women’s Health Initiative randomized trial (2006) found that healthy women who took vitamin D and calcium supplements for an average of 7 years did not have a reduced incidence of colorectal cancer. [63][72]

• In this 2013 systematic review, [39] researchers found that intervention studies did not show an effect of vitamin D supplementation on colorectal cancer occurrence. 
• To explain the consistent association of low vitamin D status with disease states, the authors suggest that inflammatory processes and clinical treatments may be responsible for the reduced 25-hydroxyvitamin D levels.

• Taken all together, the data currently available are not comprehensive enough to establish whether taking vitamin D supplements have a preventive effect on the development of cancer. [63][73] 

Cancer Studies Currently Underway

"The VitaminD/Calcium Polyp Prevention Study is testing whether vitamin D supplements, given alone or with calcium, can prevent the development of colorectal  adenomas  (precancerous growths) in patients who previously had an adenoma removed. The study’s estimated completion date is December 2017." [63][78]

"The Vitamin D and Omega-3 Trial  (VITAL) is an ongoing research study in 25,875 men and women across the U.S. investigating whether taking daily dietary supplements of vitamin D3 (2000 IU) or omega-3 fatty acids (Omacor® fish oil, 1 gram) reduces the risk for developing cancer, heart disease, and stroke in people who do not have a prior history of these illnesses." [63][74][77]

Autoimmune Diseases [54]

• Deficiencies of vitamin D interfere with D-cell (dendrites) function and contribute to autoimmunity.
• That said, vitamin D deficiency in patients with autoimmune disease may be a result rather than a cause of disease. 

Multiple Sclerosis

• "Multiple sclerosis (MS) is thought to arise due to an interplay of genetic and environmental risk factors." [53]
• Low vitamin D has been shown to be one such environmental risk factor. [52][53]
• Research suggests that a connection between vitamin D and MS could be tied to the positive effects vitamin D has on the immune system. [53]
• The link between vitamin D and MS is strengthened by the association between sunlight and the risk of MS. The farther away from the equator a person lives, the higher the risk of MS. [52]
• As well, populations with a high oral intake of vitamin D have a decreased risk of MS. [53]

Cholesterol in Post-menopausal Women [55][56]

• This 2014 study found that supplemental intake of both calcium and vitamin D in post-menopausal women significantly increased 25-hydroxyvitamin D concentrations.
• And that this led to more favorable lipid profiles, including increased HDL cholesterol (good cholesterol), lower LDL cholesterol (bad cholesterol), and lower triglycerides.

Vitamin D and its Beneficial Effects on Various Disease States

• Beyond its benefit for bone health and the prevention of rickets, the evidence for other health benefits in the general population is inconsistent. [15-17][38]

• A November 2010 report by the Institute of Medicine (IOM), which examined more than 1,000 studies and other reports, concluded that although vitamin D is essential to bone health, evidence of other benefits was inconclusive.

• A University of Edinburgh 2014 review of vitamin D and its effects on 137 health outcomes, including: skeletal, malignant, cardiovascular, autoimmune, infectious and metabolic diseases, found the only effect of statistical significance was maternal vitamin D status and birth weight:

 "On the basis of the available evidence, an association between vitamin D concentrations and birth weight, dental caries in children, maternal vitamin D concentrations at term, and parathyroid hormone concentrations in patients with chronic kidney disease requiring dialysis is probable, but further studies and better designed trials are needed to draw firmer conclusions. 
In contrast to previous reports, evidence does not support the argument that vitamin D only supplementation increases bone mineral density or reduces the risk of fractures or falls in older people.” [57]

• Land vertebrates have been making their own vitamin D for more than 350 million years. [1]

• In birds and fur-bearing mammals, vitamin D is generated from the oily secretions of the skin deposited onto the feathers or fur and is obtained orally during grooming. [61]

***

FIN

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ADDITIONAL REFERENCES

• Can Too Much Vitamin D Be Toxic? / Rachael Rettner, Senior Writer   |   May 07, 2015
• Raghuwanshi A, et al. Vitamin D and multiple sclerosis. Journal of Cell Biochemistry. 2008;105:338.
• Ramagopalan SV, et al. Expression of the multiple sclerosis-associated MHC class II allele HLA-DRB1*1501 is regulated by vitamin D. PLoS Genetics. 2009;5:e1000369. http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1000369.
• Pierrot-Deseilligny C. Clinical implications of a possible role of vitamin D in multiple sclerosis. Journal of Neurology. 2009;256:1468.
• Smolders J, et al. Vitamin D status is positively correlated with regulatory T cell function in patients with multiple sclerosis. PLoS One. 2009;4:e6635. http://www.plosone.org/article/info:doi/10.1371/journal.pone.0006635. Accessed Mar. 1, 2013.
• Weinstock-Guttman B, et al. Vitamin D and multiple sclerosis. The Neurologist. 2012;18:179. 
• http://www.scientificamerican.com/article/understanding-vitamin-d-deficiency/
• http://www.mayoclinic.org/healthy-lifestyle/nutrition-and-healthy-eating/expert-answers/vitamin-d-deficiency/faq-20058397 / Katherine Zeratsky, R.D., L.D. June 5, 2015

IMAGE CREDITS

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