Should I take Vitamin D ? How much ?

It's that time of year again in Canada, days are short and still getting shorter, light is fleeting and we are talking about Vitamin D.
In this post, I am going to answer the questions we get about Vitamin D:

• Should I supplement with Vitamin D?
• How much Vitamin D should I take?
• Should I measure my Vitamin D levels?

But first, let's get a basic understanding of Vitamin D.  If this is too much and you just want the answers, it's okay you can scroll to the bottom of this post.
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Vitamin D, the “sunshine vitamin", is a powerful hormone that your body makes through exposure to sunlight.

From an evolutionary perspective Vitamin D is one of the oldest hormones found in biology, first appearing over 500 million years ago as a cellular factor protecting proteins, DNA and RNA from UV light damage.  As organisms ventured from the oceans to land, a mechanism to obtain adequate calcium was necessary to maintain vertebrate skeletons.  Calcium is abundant in oceans but on land, it is locked in soil and only available to plants.  Vitamin D, synthesized in response to sunlight, evolved to ensure the intestinal absorption of calcium.

For many years, this was what we understood about Vitamin D: that it is essential for proper calcium metabolism and bone health. Deficiencies in Vitamin D leads to rickets, the childhood disease of bone weakness, bowed femurs and tibias.  Supplementing with dietary sources of Vitamin D to prevent rickets goes back to the early 1800’s with the use of cod liver oil (high in Vitamin D) and became mainstream in the 1930’s when milk was fortified with Vitamin D.
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Vitamin D Physiology

Vitamin D3 (cholecalciferol) the hormone precursor is synthesized from 7-dehydrocholesterol in the skin  in response to ultraviolet B (UVB) rays.  UVB rays are present only during midday at higher latitudes and do not penetrate clouds. 

The time needed to produce adequate vitamin D from the skin depends on the strength of the UVB rays, the length of time spent in the sun, and the amount of pigment in the skin.

At our northern latitude, UVB strength is not adequate from October to March so we must supplement.  Very few foods naturally contain significant amounts of vitamin D (fish, shiitake mushrooms being exceptions) so obtaining adequate Vitamin D from non fortified food alone is difficult.  Even with food fortification, it is thought that most Canadians have insufficient Vitamin D levels for optimal health.

From production in the skin, Vitamin D binding protein transports Vitamin D3 to the liver where it undergoes hydroxylation to 25(OH)D - the half-life of this Vitamin D pro-hormone in the liver is 3 weeks.  25(OH) D is transported from the liver to the kidney where it is hydroxylated by 1 alpha hydroxylase (CYP27B1) to 1,25(OH) 2 D - the active form of Vitamin D.  

Both 25(OH)D and 1,25 (OH) 2 D are degraded by 24-hydroxlase (CYP24A1).

Vitamin D then acts on the intestine to increase the absorption of calcium, on the bone to increase bone resorption and increase blood levels of calcium and on the kidney to decrease calcium and phosphate excretion.

Vitamin D’s role in calcium physiology is clear and several meta-analyses have shown that supplementation with Vitamin D and calcium decrease the risk of osteoporotic fractures in older people.

More recent research has shown that Vitamin D regulates many other cellular functions:

• The Vitamin D receptor (VDR) is found in almost all human cells
• Approximately 3% of the human genome is under Vitamin D control
• The 1-alpha-hydroxylase enzyme is also expressed in extrarenal sites, including the gastrointestinal tract, skin, vasculature, prostate, brain, lungs, mammary epithelial cells, white blood cells, osteoblasts, and osteoclasts.  It is thought that this local production of 1,25(OH)2D is responsible for many of the non-calcemic health benefits that have been reported for vitamin D. 

An explosion of research has suggested the Vitamin D may prevent or be useful in treating more than 100 disorders, ranging from:

• Cancer - observational studies show linkages between Vitamin D levels and colon, breast and prostate cancer
• Immune Function - Vitamin D affects nearly every immune cell in the body.  Vitamin D is an immune modifier:
  • ​decreasing the activation of the acquired immune system.  In theory Vitamin D deficiency could increase the risk of autoimmune disease. In a large, prospective case-control study involving over seven million United States military personnel, Caucasian recruits with 25(OH)D levels below 50 nmol/L, had twice the risk for later development of multiple sclerosis.  
  • at the same time increasing the activation of the innate immune system.  The association between Vitamin D levels and viral activity has been noted and Vitamin D supplementation reduces the rate of upper respiratory infections - but
• Diabetes
  • ​For Type I Diabetes the association between Vitamin D deficiency and increased rates of diabetes is likely related to the acquired immune modification effects.
  • For Type II Diabetes Vitamin D has been shown to improve insulin secretion through effects on pancreatic beta cells as well as improve insulin sensitivity, thus the association between Vitamin D deficiency, diabetes and insulin resistance makes sense.  Further Vitamin D is know to be lower in obese individuals - the cause of this association is not clear but some evidence points to obesity (and genetic causes for obesity) decreasing Vitamin D levels and not low Vitamin D levels causing obesity.
• Depression and Neuropsychiatric conditions - both the VDR and 1-alpha hydrolase enzyme are expressed in the brain and Vitamin D has been shown to be involved in neuronal proliferation, differentiation, migration, and apoptosis.  Low levels Vitamin D are frequently found in depression and Alzheimer’s disease, and pre-natal Vitamin D deficiency is though to increase risk of schizophrenia.
• Hypertension and Cardiovascular Disease - Vitamin D has been shown to regulate the renin-angiotensin system, and in mice Vitamin D deficiency results in high renin hypertension and cardiac hypertrophy. As well, Vitamin D exposure results in a "favorable cardioprotective” gene response in vascular endothelial and smooth muscle cells, with corresponding decrease in thrombogenesis (clot formation) and increased fibrinolysis (clot breakdown).  The mechanisms likely underlie the association that is seen between Vitamin D deficiency and increased rates of heart attacks and strokes.
• Muscle Strength - again observational studies show a relationship between muscle strength and Vitamin D levels in both children and older adults.
• Inflammation & Oxidative Stress - low levels of Vitamin D are associated with inflammation and oxidative stress.​
• All Cause Mortality - epidemiological studies suggest that low Vitamin D is associated with higher mortality.

All this evidence makes one thing clear - blood levels of Vitamin D are a good indicator of health across many conditions; what is less clear is whether low levels of Vitamin D cause poor health outcomes or whether the poor outcomes themselves can decreases in Vitamin D.  The only way to determine this is through well designed double-blind supplementation trials, which are expensive and difficult to do properly.  Still for many of these conditions trials are underway to determine the potential causal role of Vitamin D in many conditions.

There are many factors that lead to signifiant variation in blood levels of Vitamin D:

• Skin pigmentation; Dark skin reduces penetration of ultraviolet rays from sunlight and thus lowers vitamin D production.
• Northern exposure: In Canada, blood levels of vitamin D drop markedly in the winter because the strength of the UVB rays are simply not strong enough to produce Vitamin D
• Time of day and cloud cover: The sun’s ultraviolet rays are strongest mid-day, between 10 a.m. and 3 p.m. Clouds and smog absorb UVB and decrease Vitamin D production.  Glass also blocks UVB so sitting behind a sunny window does not help.
• Age: The skin’s ability to manufacture vitamin D declines with age. On average, a 70-year-old synthesizes only about one-quarter as much vitamin D as a 20-year-old from the same sun exposure. This is partly due to changes in the structure of the skin. In addition, the liver and kidneys are not as efficient in converting vitamin D to its active form, and vitamin D is not absorbed as well from the intestine.
• Sunscreen:  Sunscreens filter out or block ultraviolet rays and prevent the production of vitamin D. A sunscreen with a sun protection factor (SPF) of 15 reduces the production of vitamin D by 99 percent.
• Dietary Intake:  Since most non-fortified food does not contain Vitamin D, it is difficult to maintain adequate Vitamin D levels without supplementation.
• Obesity. Obese people have lower blood levels of D and need greater supplementation.
• Medications. Certain drugs—notably anticonvulsants, corticosteroids, and some HIV medications—reduce vitamin D levels.
• Disorders that impair fat absorption or liver or kidney function:  Vitamin D is a fat soluble pro-hormone needs absorbed in the intestines, any disorder that affects fat absorption (such as Crohn’s or celiac disease and cystic fibrosis) can reduce vitamin D levels. Some types of gastrointestinal surgery (such as gastric bypass for obesity) can also lead to D deficiency.
• Genetics. Twin studies show a high degree of heritability of Vitamin D levels.  Various genetic mutations that influence the body’s ability to produce and utilize vitamin D.
  • ​Four significant variants near or in genes involved in 
    • Vitamin D synthesis
      • rs12785878, near DHCR7 - 7 Dehydrocholesterol Reductase gen*
      • rs10741657, near CYP2R1 - Vitamin D hydroxylase*
    • Vitamin D transport
      • rs2282679, in GC - Vitamin D Binding protein*
    • Vitamin D Breakdown
      • rs6013897 in CYP24A1 - Vitamin D 24 Hydroxylase

(* available in the Molecular You Assessment)

​So at this point we have established:

• Vitamin D is more than just an important hormone necessary for healthy bones, it is linked to cellular function in nearly all human tissues.
• Low levels of Vitamin D are associated with over 100 conditions as well as increased all-cause mortality.
• Many factors result in variation of Vitamin D levels
• Food is not an adequate source of Vitamin D
• In Canada, Vitamin D supplementation is necessary, at a minimum, between October and March

So the next question is how much Vitamin D should I take?

This is where things get a bit controversial.

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If we look at disease association data, the optimal Vitamin D 25(OH)D blood levels appears to be between 100 - 150 nmol/L (40-60 ng/ml)

The venerable Institute of Medicine (IOM) stated in their 2010 guidelines that levels of 50 nmol/L ( 20 ng/ml) are adequate.

At Wellness Garage, we are most comfortable when clients are in the 100 - 150 nmol/L (40-60 ng/ml) and recognize that levels of >200 nmol/L (80ng/ml) are potentially toxic.

So how much Vitamin D do you have to take to reach this level?
Again this is controversial…

The IOM bumped its recommended dietary intake from 400 to 600 IU for adults and for 800 IU for age >70 years.  The maximum level was set at 4000 IU.

Many, including us at Wellness Garage, think these recommendations are low.

For those who have not been tested for Vitamin D, we recommend 2000 IU per day.  For anyone taking doses greater than 5000 IU we also recommend testing.

For those who can afford testing, we recommend getting tested during the winter December to February and adjusting your supplementation based on the results.

Vitamin D testing is no longer a medically insured service in most parts of Canada due to the cost, especially when a simple one size fits all recommendation to supplement will likely help most people.  We think this makes sense from a public policy perspective, at least until there is better evidence to support that supplementation itself prevents or reverses disease. 
 
We do think that individuals who are looking to optimize their health should test as there are simply too many variables to ensure that a standard dose of Vitamin D will put you in the optimal zone AND we feel that while the causal role of Vitamin D has not been proven for most conditions, it is one of the most important health indicators and the potential benefit of optimizing Vitamin D levels outweigh the negligible risks with supplementation when guided by testing. 

So if you skipped over most of this to find the answers to your questions - here is a quick summary:

• Should I supplement with Vitamin D?  In Canada - between October and March absolutely.
• How much Vitamin D should I take?  If you cannot afford testing (or don't want to get tested) we recommend 2000 IU per day.
• Should I measure my Vitamin D levels?  Yes - there is good evidence to suggest that there is an optimal range and  variability of Vitamin D levels vs Vitamin D dosing is considerable - the only way to optimize is to measure.