Chapter 2
Finding Out If You Have Enough Vitamin D
In This Chapter
Understanding how much vitamin D the body needs
Measuring the levels of vitamin D in the body
Watching out for vitamin D deficiency in children
Identifying populations that lack vitamin D
Recognizing testing problems
Now that you know what vitamin D is, and you have an idea about what calcitriol (active vitamin D hormone) does, you want to know whether you have enough of it. Finding out is a simple task, right? Not so!
To answer that question, scientists have to conduct careful studies to figure out what exactly “enough” is. First they have to prove that there is a direct relationship between vitamin D and a healthy outcome. After that they have to do studies with a range of vitamin D levels in the diet to find the exact amount needed to prevent diseases. To make matters more complicated, with all the new roles for vitamin D, they may find that the level needed to prevent rickets is different than the level needed to avoid heart disease. And they might discover that the level needed to prevent one cancer actually causes another cancer. Unfortunately the studies that have been done so far haven’t answered the question of exactly how much vitamin D we need for all of its functions; still, there’s a lot of great research that has been done, and in this chapter I explain how it was used to set dietary requirements for vitamin D.
You can get vitamin D from your diet and also after the sun stimulates your skin to make vitamin D. Because of this, the best way to know for certain whether you have enough vitamin D in your body is to get a specific blood test that measures 25-hydroxyvitamin D. Unfortunately, tests that measure this form of vitamin D can vary in accuracy and are expensive. You want to make sure that you use the best test available so that you get the most accurate results. In this chapter, you find out what scientists currently know about how much vitamin D you need and how to measure your levels properly.
How Much Do You Need, Anyway?
This question can be asked in several ways:
What level of the serum 25-hydroxyvitamin D3 in the body avoids any of the problems associated with vitamin D3 deficiency?
How much time in the sun will help you reach the necessary blood level of vitamin D3?
How many international units (IU) of vitamin D do you need to get in food or from supplements to reach the necessary blood level of vitamin D3?
Of course, the answer to the last two questions depends on the answer to the first question. Have I got you sufficiently confused? Time to get it all straightened out.
Types of research scientists use to determine vitamin D’s role in health
It’s not an easy question to ask “why is vitamin D important for my health and how much do I need?” Scientists can’t answer this all at once. Instead, they have to attack it from many different directions. Each type of research study has strengths and weaknesses. Here’s a summary of how research studies are done so you get an idea of how scientists are coming up with answers about vitamin D and health.
Population-based association studies: Often the first time scientists learn that a nutrient like vitamin D is important for health is from a study that looks at a large number of people and draws relationships between either the dietary levels of the nutrient or the serum level of the nutrient and some disease. These associations don’t prove that the nutrient (or lack of the nutrient) causes the disease; they just show that something interesting is there. For example, in the early days of television researchers showed that the number of TV sets in a household was related to the likelihood someone would have heart disease. This didn’t mean that TVs directly caused heart disease, but it did lead researchers to ask what might be the basis for the relationship. Later research showed that inactivity and bad eating habits were likely culprits for the TV–heart disease link.
Controlled clinical intervention studies (randomized clinical trials): When a scientist thinks there is a direct link between a nutrient (like vitamin D) and a health outcome, he sets up a study where people are given different levels of the nutrient to see if it can affect health. The best of these studies control everything about the people being studied; they compare people who are the same age, gender, race, and have similar lifestyle habits all so they make sure the outcome of the study is affected only by the nutrient. The good part of this type of study is that the results are reliable. The bad part is that they may not apply to other groups of people. For example, early on many research studies included only men, and the results were thought to apply to women. We’ve since learned that this isn’t always true. As a result, we often have to repeat studies in infants, children, teens and pre-teens, and adults of different ages as well as in both men and women.
Controlled animal intervention studies: Sometimes it’s not reasonable to ask people to volunteer for a study between a nutrient and a disease outcome. For example, without a clear benefit, it’s unethical to ask someone with cancer to use something that might not work. Similarly, sometimes it’s not feasible or cost-effective to conduct a research study in people. Prostate cancer is a good example of that; it takes 50 or more years for prostate cancer to develop, so we can’t afford to do a study that starts in kids and lasts a lifetime. Under these circumstances we use animals as models for humans. There are other advantages for using animals. For example, we can take tissues that aren’t available from human studies, such as internal organs or bones, and see how high vitamin D status has affected them. Of course, the weakness is that some aspects of animal biology aren’t the same as human biology. How many women do you know who have six or more babies like a rat or a mouse?
Controlled studies on cells: One way to prove that a nutrient directly influences a disease is to show that it regulates the cells from the tissue affected by the disease. By doing these types of studies we’ve learned that calcitriol influences only cells that contain the vitamin D receptor. That’s why absorption of calcium from the diet through the intestine is sensitive to active vitamin D. We’ve also learned that the cells from some tissues can turn 25-hydroxyvitamin D into active vitamin D. This helps us understand why high levels of 25-hydroxyvitamin D may protect against certain forms of cancer. The beauty of these studies is that they allow scientists to prove that direct mechanisms are in place to explain how vitamin D could affect health. The down side is that these detailed mechanisms may not work in a more complex setting like a whole person.
Knowing what level of vitamin D your body needs
Scientists believe that the serum level of 25-hydroxyvitamin D is critical for protecting health. Because of this, when you go to your doctor to figure out whether you have enough vitamin D in your system, they do a blood test for this form of vitamin D. The idea is that when you have enough 25-hydroxyvitamin D floating around in your blood, you will be able to make all the calcitriol that you need, and as a result you will have the strongest bones, and you may also have a healthy immune system, protection against several cancers, reduced rates of diabetes, and lower risk of heart disease. I discuss the importance of vitamin D for all these conditions, and several others, later in the book.
In late November 2010, an expert panel of scientists published a detailed report that explains how much 25-hydroxyvitamin D you need in your blood and provides recommendations for how much vitamin D you need in your diet to get to those serum levels. Table 2-1 shows critical levels of serum 25-hydroxyvitamin D based on this report.
Whereas the clinical labs in the United States report your blood levels of 25-hydroxyvitamin D as nanograms per milliliter (ng/ml), Canada and many other countries express serum 25-hydroxyvitamin D levels in nanomoles per liter (nmol/L). Don’t get confused by this — just be certain what units your test result were measured in. To turn nmol/L into ng/ml, all you need to do is divide the nmol/L value by 2.5.
You may notice in Table 2-1 that the levels are associated with bone health. That’s because the expert panel felt that only the evidence to link dietary vitamin D or serum 25-hydroxyvitamin D to protection from rickets, osteomalacia, low bone mass, and osteoporosis was strong enough. This doesn’t mean that they thought the relationship between vitamin D and all of those other diseases isn’t true. Instead, they determined that there just wasn’t enough evidence to be sure that vitamin D was protective. In fact, they want to see more research done so we can better see the relationship between dietary vitamin D or vitamin D status and diseases like cancer.
Some scientists researching vitamin D disagree with the expert panel; they feel that you need greater amounts of serum 25-hydroxyvitamin D in your circulation if you want to get optimal protection from vitamin D. Table 2-2 shows their suggestion.
The rationale behind these higher recommendations lies in a difference of opinion on how these scientists interpret research studies. These people base their opinion more on studies that associate serum 25-hydroxyvitamin D to health outcomes like cancer or heart disease. For example, a study published in the February 2009 issue of the Journal of Clinical Endocrinology and Metabolism showed that individuals with lower levels of 25-hydroxyvitamin D were three times more likely to die of heart failure and five times more likely to die of sudden heart death than those whose vitamin D level was at least 30 ng/ml (75 nmol/L).
However, critics of these scientists think they’re too willing to accept studies that report positive relationships between vitamin D and health, and too dismissive of other studies that suggest high levels of vitamin D aren’t effective or might be harmful. In other chapters in the book I explain how to make sense of this disagreement.
Computing the correct IU level
So, if you should have a blood level of 25-hydroxyvitamin D of at least 20 ng/ml (50 nmol/L), how much vitamin D do you need in your diet to get there? In this section, I delve into some mathematics to help you understand how to get there.
Working backward to establish vitamin D levels
When possible, scientists set recommendations for dietary vitamin D intake from research studies that show how so-called functional endpoints change when dietary vitamin D is increased. Sometimes they also find the serum level of 25-hydroxyvitamin D that gives the best level of a functional endpoint and then calculate how much dietary vitamin D is needed to reach that specific serum level. In this section I show you how this works. But first, consider three examples of functional endpoints that were used to set the current vitamin D requirement.
Parathyroid hormone: Without sufficient vitamin D, parathyroid hormone levels begin to rise in the blood. This is called secondary hyperparathyroidism and can occur, for example, in kidney disease when the kidneys can no longer make calcitriol (active vitamin D). It occurs also in elderly people who have poor nutritional intake of vitamin D. The relationship between parathyroid hormone and vitamin D was the first one to get scientists excited about the need for higher vitamin D status.
Calcium absorption: Calcitriol is a strong regulator of intestinal calcium absorption. We’ve known for many years that when a person is severely vitamin D deficient, they can’t make enough calcitriol, and the level of calcium absorption becomes very low. However, although an early study suggested you might absorb calcium from the diet better if your serum 25-hydroxyvitamin D levels were as high as 32 ng/ml (80 nmol/L), more recent studies suggest that isn’t necessary.
Bone mineral density or bone fractures: Bone mineral density provides a third functional endpoint that is strongly related to the likelihood you’ll break a bone if you fall.
As Table 2-1 showed, the expert panel that set the vitamin D requirement in 2010 felt that when you looked at all the research data together, serum PTH, intestinal calcium absorption, and bone mineral density or fractures are all protected when your serum 25-hydroxyvitamin D levels are 20 ng/ml (50 nmol/L).
Most of the information we have on the relationship between dietary vitamin D and serum 25-hydroxyvitamin D comes from studies on adults. These studies show that there’s not a simple linear relationship between the two factors. They find that if you have low serum 25-hydroxyvitamin D levels you need very little dietary vitamin D to get to 20 ng/ml (50 nmol/L) — just 600 international units (also called IU) are needed to get and keep you there. If you don’t get any vitamin D from exposing your skin to the sun, you’ll need to get all of it from diet or supplements. I talk more about that in another chapter.
Based on what I just said you can calculate that every 30 IU of vitamin D you consume will raise your serum 25-hydroxyvitamin D by 1 ng/ml (600 IU divided by 20 ng/ml) or 2.5 nmol/L. Unfortunately it isn’t as simple as that. You see, after you have 20 ng/ml (50 nmol/L) of 25-hydroxyvitamin D in your blood, your body changes the way you use the vitamin D from the diet. At that point it takes a lot more vitamin D to raise your serum 25-hydroxyvitamin D levels — to raise your serum 25-hydroxyvitamin D from 20 to 30 ng/ml (50 to 75 nmol/L) you would need an additional 900 IU per day or more! (That’s 600 IU + 900 IU or 1,500 IU per day total to get your serum levels to 30 ng/ml [75 nmol/L].)
Checking out the government’s recommendations
The last time recommendations for daily intake of vitamin D were revised was in November 2010. This was done by an expert panel formed by the Food and Nutrition Board of the Institute of Medicine of the National Academies of Science.
The recommendations are called Dietary Reference Intakes, or DRIs. When the expert panel sets the vitamin D requirement, they actually set three different values:
Recommended daily allowance (RDA): This is the average daily intake level that is determined to be sufficient to meet the nutrient requirements of nearly all healthy people. An RDA is set only if very good studies have been conducted and are available in the medical literature.
Adequate intake (AI): When studies aren’t available or aren’t definitive enough to develop an RDA, a best-guess estimate is set at a level assumed to ensure adequate nutrition; however, if there’s no evidence at all, they won’t even set an AI.
Tolerable upper intake level (UL): This is the maximum daily intake that research shows is unlikely to be harmful to health. A person is advised not to go above this intake level.
Based on a careful review of all the studies available, the expert panel came up with the recommendations shown in Table 2-3.
These dietary levels are similar to those set by two other groups.
For example, in 2008, the American Academy of Pediatrics issued new recommendations for vitamin D. Based on the available evidence , they recommended that breastfed infants should receive 400 IU each day until they’re weaned from breastfeeding; at that point, they should receive enough vitamin D-fortified milk to obtain 400 IU daily. Children who don’t obtain 400 IU through milk intake need to receive a supplement.
At the other end of life, the International Osteoporosis Foundation recommends that older adults get 800 to 1,000 IU vitamin D per day to help protect their bones and prevent osteoporosis.
The UL for vitamin D was set because of concerns about the possible ill effects caused by regular, long-term consumption of high vitamin D doses. In the following section, I explain the risks that come with very high doses taken short term. However, the expert panel was troubled by several studies that showed there are greater risks of death and chronic disease associated with long-term high vitamin D intake.
What is a “natural” vitamin D level?
Some people are unhappy with the new dietary requirements for vitamin D. For the most part, they are more comfortable basing their recommendations on associations between serum 25-hydroxyvitamin D and a health outcome. However, they also argue that higher serum 25-hydroxyvitamin D levels are more “natural.” This opinion is based on two major observations:
Serum 25-hydroxyvitamin D levels of 120 to 150 nmol/L (60 ng/ml) should be the standard because this is the serum level of people who spend all their time outdoors (like roofers and construction workers).
You can make 10,000 to 20,000 IU of vitamin D3 in your skin each day if you spend the whole day outside in the summer.
Still, this position isn’t universally accepted. The counterargument is that
The estimates of 10,000 to 20,000 IU per day come from Caucasian skin exposed to full sunlight in a controlled setting; this exposure normally results in a sunburn.
Blood levels greater than 120 nmol/L are seen only in Caucasians who work outdoors during the summer months. But Caucasian skin didn’t evolve for full-strength sunlight exposure year-round; African-American skin did. Among communities of dark-skinned people who spend much or all of their time outdoors while wearing little clothing, the typical 25-hydroxyvitamin D blood level is 40 to 60 nmol/L.
Caucasian skin evolved in Northern European latitudes where the blood 25-hydroxyvitamin D levels rise in summer and fall in winter. This suggests that Caucasians may have adapted to make enough vitamin D during summer to last the winter, not that they need to be there all year long.
Of course, like most scientific arguments, the only way to settle the matter is with controlled research.
Avoiding a vitamin D overdose
Overdosing on vitamin D isn’t easy, but it is possible if you’re taking supplements. In contrast, your body doesn’t allow overdosing from the sun alone. When your serum 25-hydroxyvitamin D levels reach 60 ng/ml (150 nmol/L), your skin stops allowing the production of vitamin D. This is why people who spend a lot of time outdoors, like roofers and lifeguards, have serum vitamin D levels in that range but not higher.
You can get vitamin D intoxication if you take a very large dose for a prolonged period of time, or a huge dose for a short time.
Vitamin D intoxication involves some specific and nonspecific symptoms:
Confusion
Marked thirst and dehydration
Increased urination
Constipation
Heart rhythm abnormalities
Nausea
Poor appetite
Vomiting
Weakness
Weight loss
To really know if these symptoms are due to vitamin D toxicity, you need to get some tests done at your doctor’s office. These tests show:
Elevated levels of calcium in the serum and urine
Elevated level of 25-hydroxyvitamin D, usually more than 150 ng/ml (375 nmol/L)
Parathyroid hormone level usually undetectable
If the toxicity is allowed to continue for more than a few days, the person faces a risk of permanent kidney damage as well as death from heart arrhythmias, dehydration, and abnormal blood salt (electrolyte) levels. Calcium may also be laid down like bone in many areas of the body where it isn’t usually found, such as the lining of blood vessels, thereby increasing the risk of heart attack and stroke.
Instances of vitamin D overdose have occurred, but they’ve generally been inadvertent. Consider a few examples from the medical literature:
Twenty people in Massachusetts got vitamin D toxicity from their milk when a worker at a local dairy put way too much vitamin D into milk. Milk is normally supplemented with 100 IU vitamin D3 per cup, but the milk from this dairy had as much as 50,000 IU per cup. All of the people who came down with vitamin D toxicity after drinking this milk were heavy milk drinkers. Luckily everyone recovered after this mistake was corrected.
A two-year-old boy was given an ampule of vitamin D a day instead of two drops. Each ampule contained 600,000 IU; he received four ampules, or 2.4 million IU. The boy developed severe high calcium, colic, and constipation. He recovered fully after the improper dosing stopped.
A 60-year-old man was taking a supplement that hadn’t been properly diluted. He was taking 1 million units daily. The man experienced some nausea and elevated calcium that improved as soon as he stopped the supplement, with no long-term adverse effect.
A health guru taking his own Ultimate Power Meal became sick with nausea and constipation. He found that the manufacturer of his meals had been erroneously putting 2 million IU in each meal. Some of his customers suffered kidney damage, but the guru didn’t.
Measuring Vitamin D in the Body
If you want to know whether you have enough vitamin D in your body, you must have a blood test for 25-hydroxyvitamin D. At first glance, this doesn’t seem correct, because this compound isn’t calcitriol or active vitamin D (1,25(OH)2 vitamin D). You’d think that measuring calcitriol gives you a more accurate picture, but it doesn’t for several reasons. First, 25-hydroxyvitamin D is more stable than active vitamin D, so it reflects vitamin D status over the course of the last month. Whereas newly made calcitriol lasts only a few hours in your body, 25-hydroxyvitamin D lasts two to three weeks.
Another reason is that as your body becomes deficient in vitamin D, it turns on the production of calcitriol to maintain its level — it’s only when most of the body’s vitamin D is used up that calcitriol levels finally begin to fall. By that point, the body is very deficient in vitamin D.
Depending where you live, you may have trouble convincing your doctor to order a vitamin D test for you. Insurance pays for it, but because of the high demand over the past few years, in some parts of the United States and Canadian the test is no longer covered because the cost was escalating enormously and the labs were getting overloaded. If you can’t get the test done, you may have to take a vitamin D supplement just to be safe. On the other hand, if you do have the test done, your doctor will be able to tell you whether your serum 25-hydroxyvitmain D level falls within the “normal” range. You just have to pay attention as to whether the lab uses the same reference range I described in this chapter. If your serum 25-hydroxyvitamin D level isn’t high enough, your doctor will have you take a supplement to build up your level. Then your doctor should test you again in a few months to make sure your serum levels are high enough.
Remember, serum 25-hydroxyvitamin D levels can be reported either as nanograms per milliliter (ng/ml) or as nmoles per liter (nmol/L). Don’t be confused if you see the value either way.
The current definitions of levels of vitamin D are:
Deficient: Less than or equal to 10 ng/ml (25 nmol/L)
Insufficient: Between 10 ng/ml and 20 ng/ml (25 to 50 nmol/L)
Sufficient: More than 20 ng/ml (50 nmol/L)
There is some evidence that even higher serum 25-hydroxyvitamin D levels, more than 30 ng/ml (75 nmol/L), may help protect you from chronic diseases like cancer and diabetes. This is controversial but we’ll discuss this in Part III.
If your level is insufficient, your doctor will recommend that you start taking a vitamin D supplement to get your levels up. If your level is deficient, your doctor will put you on a high repletion dose of vitamin D — probably 50,000 IU once a week for a month. This will raise your serum vitamin D levels quickly and put them in a healthy range.
Checking Children for Proper Vitamin D Levels
Adequate levels of vitamin D are essential for children before birth, after birth, and throughout childhood to ensure the proper development of bones and teeth. If they get enough vitamin D throughout childhood, they may avoid problems in adulthood, such as osteoporosis.
The recommended optimal level of 25-hydroxyvitamin D in children is the same as in adults — 20 ng/ml (50 nmol/L). The best way to check children for vitamin D deficiency is with a blood test for 25-hydroxyvitamin D.
Risk factors for low vitamin D in children include:
If their skin is naturally dark, such as people who are of African, Hispanic, or Southeast Asian descent
If their skin is regularly covered, such as due to religious or cultural reasons
If they are being breastfed exclusively
If they drink milk less than once a week
If they are obese
If they live a sedentary lifestyle that limits outdoor activities
If they live in a place with a long winter
Delivering the right daily dose for kids
The new Institute of Medicine vitamin D recommendations for kids range from 400 to 600 IU daily. This is consistent with the American Academy of Pediatrics Guidelines for infants, children, and adolescents. That organization suggests that the following groups receive a daily supplement of vitamin D:
Breastfed and partially breastfed infants
Nonbreastfed infants and older children drinking less than a quart per day of vitamin D-fortified milk
Children with an increased risk for vitamin D deficiency, such as those taking certain prescription medications including anticonvulsants that reduce vitamin D activity
Adolescents who don’t obtain enough vitamin D daily through food
Many kids have a good vitamin D status because of the sun exposure they get as part of an active lifestyle (see Chapter 11).
Children who have fat malabsorption, including cystic fibrosis and inflammatory bowel disease patients, should receive their vitamin D by injection subcutaneously or intramuscularly.
Treating children for deficiency
Actual treatment of vitamin D deficiency in infants and adolescents requires much higher doses for a period of time. Doctors give patients 2,000 to 4,000 IU daily for three to six months, monitoring their blood 25-hydroxyvitamin D levels regularly to prevent toxicity.
After sufficient vitamin D is given, the abnormalities rapidly reverse. The following improvements occur:
The serum 25-hydroxyitamin D level rises to 20 ng/ml (50 nmol/L) or higher.
Low serum calcium and phosphorus levels rapidly correct within six to ten days.
Parathyroid hormone level, which had risen because of the low serum calcium, falls to normal within one to two months.
Healing of rickets occurs in three to six months, depending on the severity of the disease.
Figuring Out Who Lacks Vitamin D
Because most people don’t take supplemental vitamin D, two major forces determine the vitamin D content of the body: the latitude where you live and the amount of pigmentation in your skin.
If you draw a line between the northern border of California and Boston, you’ll be approximately on the line of 42 degrees north latitude (see Figure 2-1). People who live above that line don’t get enough ultraviolet exposure between the months of November and February to make vitamin D. As you proceed farther north, there are even fewer months in which you can make vitamin D. People who live below 34 degrees north, a line between Los Angeles and Columbia, South Carolina, still make less vitamin D in the winter, but it’s less of a problem. The number of people who lack sufficient vitamin D is surprisingly high, even at that sunny latitude.
Other factors that reduce vitamin D production are altitude, cloud cover, smog, skin melatonin levels, and sunscreen application. High levels of these factors will all reduce skin vitamin D production.
The following sections describe the 25-hydroxyvitamin D status of various groups.
Figure 2-1: How much vitamin D you make in winter depends on where you live.
Caucasians
Despite studies suggesting that Caucasians can make up to 20,000 IU after 60 minutes in the summer sun, a large percentage of them lack sufficient blood levels of 25-hydroxyvitamin D. Vitamin D levels for all groups vary according to the latitude where they live. But studies show that about 12 percent of young adult Caucasians have serum 25-hydroxyvitamin D levels less than the desired 20 ng/ml (50 nmol/L). The percentage with reduced 25-hydroxyvitamin D levels doubles when you look at people older than 60.
Your skin has only enough precursor to make about 10 to 20,000 IU of vitamin D3 during the first 30 to 60 minutes of sun exposure. After that, you’ll just burn.
African Americans
As the group with the greatest amount of skin pigmentation, African Americans have the lowest serum 25-hydroxyvitamin D levels. As many as 80 percent have suboptimal levels of vitamin D (serum 25-hydroxyvitamin D levels less than 20 ng/ml [50 nmol/L]). This problem occurs because the melatonin in African Americans’ skin blocks the UV light needed to form vitamin D. African Americans require five to ten times as long in the sun as Caucasians to reach similar levels of vitamin D production in the skin. African Americans have low levels of vitamin D even when they expose themselves to the sun for hours a week or work in a job where they’re outdoors all day. The lowest 25-hydroxyvitamin D levels are seen in African Americans living at latitudes far from the equator. Because skin pigmentation prevents damage from sunlight exposure but also reduces vitamin D synthesis, unpigmented skin is probably best adapted for latitudes far from the equator (where UV penetration is weaker except during summer) whereas more deeply pigmented skin is best adapted for latitudes closer to the equator (where UV penetration is intense year-round).
Some doctors believe that lower levels of vitamin D in the blood of African Americans contribute to their decreased overall health when compared to Caucasians. It’s clear that African Americans get more breast cancer, colon cancer, and prostate cancer than Caucasians, and these cancers also tend to be more aggressive. But that could be coincidence. Research is on-going to make the causal links between low vitamin D and chronic diseases in African Americans. But until we have that evidence we won’t know whether vitamin D is a magic bullet to improve the health of this specific group of people or just a casual association.
Asian Americans
Asian Americans are also at high risk of vitamin D deficiency, both because of their skin pigmentation and because many of the women wear dresses that cover them from head to toe, leaving no area visible for sun exposure. In various studies, about 40 percent of Asian Americans have suboptimal vitamin D status (serum 25-hydroxyvitamin D levels less than 20 ng/ml [50 nmol/L]).
Asian-American women are especially at high risk of osteoporosis because they start out with a low bone mass and bone density. They often consume less calcium than other women, and eat high amounts of foods that contain a chemical called phytate (found in leafy greens) which blocks calcium absorption. They often have lactose intolerance as well, which means they can’t consume dairy products that are higher in calcium and vitamin D.
Latinos
Despite often living in sunny latitudes, Latinos have a suboptimal level of vitamin D (serum 25-hydroxyvitamin D levels less than 20 ng/ml [50 nmol/L]) that is similar to Asian Americans, at about 40 percent. A major reason for this decline in vitamin D among both Latinos and African Americans may be the increasing obesity in both groups: Fat holds on to vitamin D and doesn’t release it into the circulation.
Children
Children especially need sufficient vitamin D for proper bone growth. However, although some studies have shown that the skeleton will be normal in length, mass, and calcium content at birth in children born of the most severely vitamin D-deficient women (such as women with rickets or osteomalacia), other associational studies suggest that babies born from mothers who have inadequate levels of vitamin D may have lower bone mass at birth than babies born of mothers with higher vitamin D levels.
The discrepancy among these studies may be due to the problem of associational studies — in this case the association hides the fact that women with lower vitamin D levels during pregnancy are more likely to have poor nutrition, be of lower socioeconomic status, be overweight or obese, and so on, and that these factors may affect the fetal skeleton’s growth without vitamin D playing a role itself. Still, as I make clear in later chapters, lower vitamin D levels during fetal development may have effects not just on bone, but on many other important tissues as well.
After birth, the baby’s skeleton becomes dependent on vitamin D and calcitriol for continued growth and mineralization. Studies indicate that 25-hydroxyvitamin D levels in children are similar to those of the adults of their ethnicity:
Ten to twenty percent of Caucasian children are low in vitamin D.
Sixty to eighty percent of African-American children are low in vitamin D.
Forty percent of Latino children are low in vitamin D.
The elderly
As people age, they become less efficient at making vitamin D in their skin, and they are more likely to avoid sun because they’re less active or mobile, and they’re concerned about skin cancer. Still, with sufficient skin exposure, the elderly can make enough vitamin D to meet their needs. However, the tendency is to keep the elderly indoors in nursing homes or, when they go out, to bathe them in sunscreen and have them wear protective clothing. As a result, as many as 70 percent of the elderly population over age 70 have serum 25-hydroxyvitamin D levels less than 20 ng/ml (50 nmol/L), and as many as half of the elderly are at risk of severe vitamin D deficiency. Chapter 14 describes the consequences of this deficiency.
People who are obese
People who are overweight or obese have large stores of fat that can accumulate vitamin D. This makes overweight people have low circulating vitamin D levels. When lean and obese people are matched for the same vitamin D intake, the obese have much lower 25-hydrodyvitamin D levels. Unfortunately, you can’t get access to the vitamin D stored in fat unless you lose weight and free up the vitamin D trapped there. For more information on your needs for vitamin D, see Chapter 11.
Because vitamin D is trapped in fat, this is why oily fish and blubber are rich sources of vitamin D for those consuming a traditional, native diet in the far north!
Looking at Lab Tests for Vitamin D
In the last couple years, the number of people getting tested for serum 25-hydroxyvitamin D has skyrocketed. For example, in July 2006, the Mayo Clinic laboratory did about 19,000 chemical tests per month for 25-hydroxyvitamin D. In December 2008, it did more than 61,000 tests for 25-hydroxyvitamin D each month.
Vitamin D testing is becoming a part of routine physicals, but lab test sheets often have several forms of vitamin D on them.
The proper test to determine whether you have enough vitamin D in your body is the test for 25-hydroxyvitamin D, not the test for calcitriol nor the test for vitamin D itself.
Examining the tests
Three tests are commonly used to measure 25-hydroxyvitamin D. In this section, I tell you the ins and outs of the chemical tests and why one is better than the others.
Liquid chromatography - mass spectrometry
Liquid chromatography - mass spectrometry, abbreviated as LC-MS, is the best of the current tests. It measures both the form made from plant-derived vitamin D2, 25-hydroxyvitamin D2, and the form made by animals, vitamin D3, 25-hydroxyvitamin D3. You add the two to get the total 25-hydroxyvitamin D level.
The basic idea behind liquid chromatography is to separate a complex solution of things from one another based on their size and chemical characteristics. This is needed for a biological fluid like the serum from our blood — there are many chemicals and compounds in our blood, but in this case we only want to know how much 25-hydroxyvitamin D is there. The LC part of the assay is done within a column so that each different compound in the mixture moves through the column at a different speed, separating the compounds. In that way, the two forms of 25-hydroxyvitamin D can be separated from other compounds in the mixture.
After the compounds are separated, they can be identified and measured in the mass spectrometer. In this device, the sample is first turned into a gas. The individual chemicals in the gas are turned into charged particles by bombarding the gas with an electron beam. Because every compound has a different chemical composition, the amount of charges on each chemical in the gas differs, and this can be measured. The combination of small-size and charge differences on the chemicals makes it possible to separate 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 from one another.
The problem with the LC-MS method is that it requires a great deal of sophisticated and expensive laboratory equipment, and performing the test on large numbers of blood samples requires a great deal of time. Still, several commercial and hospital laboratories are now set up to do large numbers of tests.
Radioimmunoassay
A radioimmunoassay (RIA) uses an antibody to bind to 25-hydroxyvitamin D. Antibodies are proteins formed in the body when your immune system reacts to substances your body views as foreign. Scientists have learned how to get animals to make very specific antibodies to chemicals like 25-hydroxyvitamin D so that they can be used for medical diagnostics. A known amount of radioactive 25-hydroxyvitamin D is added to the antibody in solution. The serum sample containing 25-hydroxyvitamin D is then added. The more 25-hydroxyvitamin D is in the serum sample, the more radioactive 25-hydroxyvitamin D is displaced from the antibody. The amount of bound radioactive 25-hydroxyvitamin D is inversely related to how much 25-hydroxyvitamin D was in the original sample (i.e., a log of radioactive binding means very little 25-hydroxyvitamin D was in the serum sample).
The problem with this test is that some versions of the test don’t measure 25-hydroxyvitamin D2, and none of them separate 25-hydroxyvitamin D2 from 25-hydroxyvitamin D3. If you’re taking a vitamin D supplement as D2 but the test measures only 25-hydroxyvitamin D3 then the blood test will not show a change in your serum level of 25-hydroxyvitamin D no matter how much you take. However, for the RIA tests that do measure both 25-hydroxyvitamin D2 and D3 (but just can’t tell the difference between the two), the value you get for total 25-hydroxyvitamin D is the same for the LC-MS and the RIA tests.
An advantage of the RIA is that it requires much less sophisticated equipment than the LC-MS approach, so the test is less expensive to perform. Some experts believe that reporting the 25-hydroxyvitamin D as D2 and D3 just confuses the diagnosing physician.
High-performance liquid chromatography
High-performance liquid chromatography is the third method currently used to measure 25-hydroxyvitamin D. This method has similarities to liquid chromatography-mass spectrometry in that it separates chemicals in a complex mixture by putting the biological sample into a liquid form and passing it through a column. This method uses equipment that is just a little less sophisticated than the LC-MS method. As a result, it’s a little less efficient at separating the D2 and D3 forms of 25-hydroxyvitamin D. In addition, similar to the LC-MS method, you need a well-trained technician to run the test.
Discovering testing problems
At the end of 2008, the largest medical lab in the country sent letters to thousands of doctors stating that it had provided incorrect test results for 25-hydroxyvitamin D for the last two years. Because many doctors had sent large numbers of patients to this lab for vitamin D testing, probably tens of thousands of tests had been incorrect. Most, but not all, of the incorrect tests had been on the high side.
The lab offered to retest all the affected patients for free, but the damage, as they say, had been done. Up to that time, no comparable patient test recall had involved such large numbers.
The lab stated that the problem had arisen because it had switch-ed from a different lab technique. The new test that researchers were using was the LC-MS. Using the mass spectrometer can be difficult, particularly with large numbers of samples. In addition, some of the chemicals used to calibrate test results were faulty.
Some of the doctors who had ordered the test were perplexed. In one case, a patient who had always had deficient serum 25-hydroxyvitamin D levels suddenly came back with toxic levels. Testing in another lab showed a normal level. In another case, a black prisoner who had been in solitary confinement was found to have a normal level of vitamin D, a near impossibility.
One expert sent his own blood to six different labs several years ago and got results that ranged from 14 ng/ml (35 nmol/L) to 41 ng/ml (103 nmol/L). Clearly, something needed to be done.
Standardizing the test
In response to the confusion surrounding the testing of 25-hydroxyvitamin D, the National Institute of Standards and Technology developed Standard Reference Material 972.
Standard Reference Material 972 is made up of pooled blood samples from a wide selection of blood donors. Each pool contains different levels of 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 so that four different types of sample are represented. The amount of the two compounds in each pool was carefully measured using LC-MS.
The following pools are available:
Normal serum: Contains mostly 25-hydroxyvitamin D3
Low vitamin D serum: Contains half as much 25-hydroxyvitamin D3 as the normal serum
Supplemented serum: Consists of a sample similar to someone getting vitamin D supplements containing 25-hydroxy-vitamin D2
Child’s serum: Contains a high level of a modified form of 25-hydroxyvitamin D that has so far been found only in the serum of small children
Using these four pools of serum, a clinical laboratory can calibrate its instruments and fine-tune its techniques to get accurate measurements. If they get correct values for the four pooled samples, presumably they should get correct values for any unknown serum sample. This makes the measurement of 25-hydroxyvitamin D as reliable as possible.