Adrian Gombart, Ph.D., is the Linus Pauling Institute’s resident expert on vitamin D. The institute hosted a free webinar with him, discussing the role of vitamin D in bone health, cancer prevention, fighting infections, and supporting the immune system. We present it here, along with his follow-up answers to audience questions.

 

Originally live-streamed on August 27^th, 2015.

Audience Questions and Follow-up Answers from Dr. Gombart

Blood Levels

Which is more important: keeping vitamin D blood levels high or maintaining a constant supply through diet or sunlight exposure?

Both are important. It is important to keep your levels above 30 ng/ml by providing a constant supply of vitamin D. You can determine your status through a simple blood test done through your doctor’s office or by certified laboratories. If your serum levels of vitamin D are too low, most doctors will suggest taking a supplement to raise your levels. A follow-up blood test performed after a couple of months will allow you to determine if supplementation has raised your levels.

How quickly do vitamin D levels in the blood change after supplementation has begun?

Studies have shown that blood levels begin to change within a day of taking vitamin D, but they can take time to reach a plateau depending on the dose. Taking a maintenance dose will generally require one to two months for levels to plateau. If one takes a loading dose (i.e. a large dose once a week for five weeks), then the levels will increase more quickly and plateau.

Can you explain the differences between ng/mL and nmol/L measurements? What is more commonly reported on laboratory tests from your doctor?

Blood levels can be expressed in conventional units for the 25 hydroxy form of vitamin D that are on a weight per volume basis, or nanograms per milliliter (ng/mL). The international system (SI) units are based on number of molecules that has a unit of “mole” in a particular volume, so nanomoles per liter (nmol/L) are typically seen. The conversion factor from convention to SI units is: 1 ng/mL = 2.496 nmol/L. Thus 30 ng/mL is roughly equivalent to 75 nmol/L.

In United States the conventional units are generally used and international system units are used in most other parts of the world. We often talk about both because research articles from around the world do not always use both systems of reporting.

If my blood levels are in the ideal range, should I worry about taking additional vitamin D?

Serum levels often depend on time of year. If you get it measured in the summer and are getting a lot of exposure to sunlight (and not using sunscreen), then you are likely to have adequate levels. However, this could change in the winter months. If you get your vitamin D levels measured in January or February, that should tell how well you are doing.

Remember, vitamin D levels go down if there isn’t a steady supply to maintain them. The Linus Pauling Institute recommends a daily dose of 2,000 IU (50 micrograms) for adults, through a combination of diet, supplements, and sun exposure. Taking a supplement may be the most advisable  way to achieve this, especially during the winter months.

Is it possible that some people never reach the recommended blood levels of vitamin D even with steady supplementation? What is the best approach for those individuals?

There are individuals who have difficulty in raising their blood levels of vitamin D and genetic factors may play a role. If a supplementation regime by your doctor does not raise your vitamin D levels after several months or even a year, it is likely that there is some other factor(s) involved. Ask your doctor to look into interacting medications (above), but continue to try to get 2000 IU/day of vitamin D. In consultation with your physician, you may consider raising the level of supplementation and determine if that raises your serum levels.

Supplementation Tips

If someone is found to be deficient, what dosages typically are used to raise vitamin D levels?

If the deficiency is significant (<20 ng/ml in the blood), then physicians will frequently prescribe a 50,000 IU dose each week for 8 weeks and then reduce it to a lower dose that should be taken daily. However, different physicians may have different recommendations for supplementation – some prefer to space the doses out evenly throughout the week, for example.

The doses recommended by the IOM (600 IU for adults and 800 IU for adults older than 70) and the LPI (2,000 IU daily for adults and the elderly) are designed for maintenance of vitamin D levels in the body, not for the treatment of a deficiency.

Since vitamin D is fat-soluble, do supplements need to be taken with a source of fat to be absorbed well?

Absorption may be higher when taken with fat in the meal, particularly with high doses (50,000 IU) but, vitamin D absorption does not require food. Blood levels were not any different when people took vitamin D with a meal versus no meal.  So, data suggests that it is not necessary to take it with a source of fat or a meal, but it it does not hurt to do so if it is convenient.

Other agencies (such as the Vitamin D council) recommend much higher levels of vitamin D supplementation than the LPI.  Why do you not recommend higher amounts?

Our recommendation is based off of literature reviews. For bone health, it is important to keep serum levels above 20 ng/ml, which is the recommendation of the Institute of Medicine. While a number of studies indicate that vitamin D blood levels above 30 ng/ml or even higher provide additional benefits, there are studies that don’t support maintaining extremely high levels. Studies designed to specifically address single outcomes will provide the information needed to answer these questions.

The Endocrine Society, based on the totality of the evidence, recommends levels 30 ng/ml or higher. The LPI agrees with that recommendation, and suggests that 2000 IU per day of vitamin D is the best way to achieve it. However, whatever amount of diet, supplementation, and sun exposure gets your blood levels to this mark or higher is what you really should shoot for.

Do vitamin K and vitamin D work together? Is it beneficial to take them together as supplements?

Vitamin K is important for bone mineralization but reduces calcification of soft tissues. There are a few papers with animal studies showing that vitamin K supplementation may suppress experimental calcification of soft tissues caused by incredibly high doses of vitamin D.

There are a number of papers that suggest an important interaction between the two vitamins and that ensuring adequate levels of vitamin K and vitamin D is likely beneficial. However, the LPI does not (yet) recommend vitamin K supplements – dietary sources, like green leafy vegetables – are often adequate to achieve your daily recommended levels of K.

Instead of supplements, can I use UV lamps to promote vitamin D synthesis in my skin?

Most tanning beds emit UVB rays and thus promote vitamin D synthesis in the skin; the same goes for UV lamps that are available for commercial home use. However, all of these sources of UV light damage skin just as would over-exposure to the sun and can cause skin cancer (more on indoor tanning from the CDC). Thus, the LPI recommends using supplements to maintain vitamin D levels to avoid the health risks associated with indoor tanning.

There are certain conditions (cystic fibrosis or short bowel syndrome, for example) where oral supplementation would not work as individuals are unable to absorb vitamin D from the diet or supplements. A commercial portable indoor tanning lamp that mimics the spectral output of natural sunlight or possibly giving large doses of vitamin D by injection may be used, but both of these options should be used only in consultation with a physician.

Supplement Forms

What’s the difference between vitamin D₃ in a micro-encapsulated vs. non-micro-encapsulated form?

The most common reason for micro-encapsulating vitamins is to extend shelf-life or to allow for easier fortification of particular foods or liquids. The micro-encapsulated vitamin D3 is designed to be more heat-stable and allow for easier incorporation into foods or blends that will receive some heat. Both forms are the same once the molecules are released from the encapsulation material. They are absorbed in the small intestine and taken up in the blood.

In treating deficiency, is vitamin D₂ used more often than vitamin D₃ (or vice-versa)?

Both vitamin D2 (form derived from fungi) and D₃ (form derived from animals and synthesized in our own skin) are used to treat deficiency, but the D₃ form is often recommended as it raises blood levels more effectively. Vitamin D₃ stays in the circulation longer than vitamin D₂, which could mean that supplementation would need to be at higher doses and more often to compensate.

Is there any difference between natural and synthetic vitamin D? Do vitamin D₂ and vitamin D₃ have the same effect on tissues (potency), even if the half-life in the body is different?

Both natural and synthetic forms are produced by exposing either ergosterol (for vitamin D₂) or 7-dehydrocholesterol (for vitamin D₃) to UVB rays. Natural would involve sunlight and synthetic would involve UVB rays produced by artificial light. Both natural and synthesized forms of vitamin D₂ or D₃ are chemically identical and behave the same in the body. The only difference is the source.

Health Effects

Is there any evidence to suggest that high blood vitamin D levels can help prevent cancer?

There are numerous studies associating low vitamin D levels with increased rates of cancer, in particular colorectal, breast, prostate, leukemia and lymphoma. Also, many pre-clinical studies support the role of vitamin D in killing cancer cells. However, there is insufficient data to conclude that taking vitamin D supplements will prevent cancer in people. Definitive evidence from large trials is still needed.

There as are several studies underway that hope to provide the answer to this question, including the Vitamin D/Calcium Polyp Prevention Study and the Vitamin D and Omega-3 Trial.

Are there any epigenetic effects of vitamin D?

Yes, the gene for the vitamin D receptor and some of the enzymes that regulate its metabolism have large regions of DNA that allow epigenetic changes to regulate their expression. In other words, there may be epigenetic changes (like DNA methylation) that influences that activity of vitamin D and may turn on or turn off many genes in cells. The impact of vitamin D and its receptor on epigenetic regulation is an active area of research.

How is vitamin D important for a healthy nervous system?

The totality of data from research on vitamin D and the nervous system indicate that it is important in proliferation, differentiation, neuroprotection, neurotransmission and neuroplasticity. The strength of the evidence varies for different conditions, but is particularly strong for multiple sclerosis for which recent findings indicate a protective role for vitamin D. Findings also point to roles in cognition and memory, but much more research is needed to fully understand its importance.

Would you touch on the role of vitamin D and gut bacteria? Is there anything known about supplementation and the microbiome?

Recent studies have shown that vitamin D can cause shifts in the composition of the bacteria species present in the gut in both humans and mice. As with many studies on the gut microbiome, the impact of these changes on health is unknown. Our group is interested in determining the mechanism(s) by which these changes may occur and the impact on health.

Vitamin D is important for gut health and it is possible that regulation of antimicrobial peptide expression in the gut by vitamin D leads to changes in the composition of the microbes. We recently received NIH funding to address the role of this pathway in mediating the benefits of vitamin D on gut health, the composition of the microbiota and obesity.

Does vitamin D help protect against environmental toxins (for instance, heavy metal exposures such as lead or arsenic)?

Limited data is available on this subject. It has been reported that lower dietary intake of vitamin D and vitamin C enhances the absorption and retention of lead in the body. Also, it was reported that lead interferes with the conversion of vitamin D to its active form. Recent reports found that arsenic might lower vitamin D levels, and may be associated with incidence of diabetes.

Will the dose the LPI recommends provide the immune and mood benefits attributed to vitamin D?

It is difficult to know what dose of vitamin D will provide maximum immune and mood benefits. We know that low levels are associated with an impaired immune system and poor mood, and supplementation can be beneficial in these situations. However, we don’t know exactly what level of vitamin supplements are needed to achieve benefits, and would just suggest that people keep their vitamin D levels at 30 ng/mL or higher.

Interactions

Are there any medications that are contraindicated during oral vitamin D supplementation?

It’s a good idea to tell your doctor about any supplements you are taking so that they can help you avoid adverse reactions with your prescription medications. That said, the following medications may raise levels of vitamin D and thus any supplemental vitamin D you take should definitely be discussed with your doctor:

• Estrogen given for hormone replacement therapy
• Isoniazid (for tuberculosis) and thiazide diuretics (mainly used to treat high blood pressure) can increase the activity of vitamin D and inappropriately raise calcium levels in the blood
• People taking Digoxin for irregular heart rhythms should have calcium levels monitored as vitamin D improves calcium absorption and may increase toxic reactions from this medication

Are there any medications that can alter vitamin D levels in the body?

The following medications may lower vitamin D levels:

• Antacids for long periods of time may affect metabolism or availability
• Calcium channel blockers (often used for hypertension) may decrease production of vitamin D
• Cholestyramine (for high cholesterol) can interfere with absorption of vitamin D and other fat soluble vitamins
• Anticonvulsant medications (for epilepsy, seizures, and possibly mood disorders) may increase the breakdown of vitamin D
• Mineral oil interferes with vitamin D absorption.
• Orlistat and olestra reduce absorption of fat to promote weight loss and potentially could interfere with vitamin D absorption, but this not clear.

It is advised that individuals taking medications consult with their physicians about potential interactions. For more on vitamin D and drug interactions, please consult the relevant section in the Micronutrient Information Center.

Since vitamin D is fat-soluble, I am concerned about taking too much. There are reports that taking 2,000-6,000 IU per day are toxic, and can lead to arterial calcification. Is this true?

It is true that taking incredibly high levels of vitamin D could lead to arterial calcification, but this would involve levels that are hundreds of times higher than 2,000-6,000 IU/day (more like 200,000 – 600,000 IU/day for months). Our bodies are capable of synthesizing 10-20,000 IU per day upon sun exposure and there are no reports of toxicity in individuals that spend long hours in the sun. The Institute of Medicine has set the upper intake level at 4,000 IU/day, but numerous research publications have shown that toxicity is highly unlikely in healthy individuals taking less than 10,000 IU/day.

There are certain diseases where people have to be careful about taking too much vitamin D. This includes primary hyperthyroidism and granulomatous diseases including sarcoidosis, tuberculosis and lymphomas. These diseases involve nodules packed with activated immune cells that can synthesize high levels of the active hormone form of vitamin D, so consult your doctor about taking large doses if you have any of these conditions.