The Overlooked Importance of Vitamin D Receptors

by EraOfLight

Just a few years ago, vitamin D was simply known as the “bone vitamin.” Thanks to the hard work of many scientists, especially Michael Holick, MD, a pioneer in vitamin D research, the data show that nearly every tissue and cell type in the body has receptors for vitamin D.1 As a result of this discovery, much higher doses are required for optimal functioning. This discovery has radically changed how we understand the role of vitamin D in the body.
Unless your body is at optimal levels, you are opening the door to a host of disorders, ranging from heart disease and Alzheimer’s to weak bones and diabetes.2,3
In fact, even if you have normal blood sugar today, a vitamin D deficiency makes you 91% more likely to progress to insulin resistance, or “pre-diabetes,” and it more than doubles your risk for progressing to active, type II diabetes.4
Unfortunately, vitamin D deficiency is a global epidemic. An estimated 1 billion people do not have adequate vitamin D levels.5 And 64% of Americans don’t have enough vitamin D to keep all of their tissues operating at peak capacity.6
The results of this deficiency are catastrophic. Studies have now shown that vitamin D deficiency is associated with increased risk of a long list of diseases that span all systems in the body. In fact, low levels of vitamin D increase the risk of non-Alzheimer’s dementia almost 20 times! 7
While checking for vitamin D levels is still not standard of care for many physicians, you will realize from reading this article that assessing vitamin D status is one of the most important health-protecting steps you can take. Fortunately, achieving optimal levels of vitamin D is easy, inexpensive, and highly protective against a range of lethal diseases.
Why Vitamin D is so Vital
While humans can make some vitamin D in their bodies, most of us require additional amounts from our diet, the sun, or from supplements in order to maintain adequate levels.
Once vitamin D has been ingested in the diet or produced in the skin, the liver and kidneys convert it to its active form, called 1,25-dihydroxyvitamin D, or vitamin D3.8,9
Virtually every tissue type in your body has receptors for vitamin D, meaning that they all require vitamin D for adequate functioning.8,9 The very presence of specific receptors define vitamin D as a hormone, rather than a vitamin.8 It interacts with receptors throughout the body and has a number of different effects.
It’s becoming evident that higher doses of vitamin D are required to support its other activities in tissues such as heart muscle, brain cells, and fat tissue, to name just a few. Additionally, vitamin D regulates genes that control cell growth and development, immune function, and metabolic control. 5,8
Studies have now shown that vitamin D deficiency is associated with increased risk of numerous chronic disorders, including type II diabetes, cancer, infections, and cardiovascular, autoimmune, and neurological diseases (See the table on page 2 for greater detail).8,9
The Global Vitamin D Deficiency
The problem is that most of us are simply not getting enough vitamin D to allow our bodies to work optimally at all of the functions that vitamin D supports. An estimated 1 billion people (that’s about a seventh of the global population) have inadequate vitamin D supplies in their bodies.5
According to mainstream medical standards, there are three levels of vitamin D status: sufficient, insufficient, and deficient.
By those criteria, 25% of Americans are insufficient, and 39% are outright deficient.6 In other words, fully 64% of Americans don’t have enough vitamin D to keep all of their tissues operating at peak capacity. It’s hardly any wonder we are plagued with so many chronic diseases.
Vitamin D Supports Cardiovascular Health
Vitamin D deficiency is common in people with cardiovascular disease; almost all people with heart failure have reduced levels.10 It is now recognized as an independent predictor for diseases of the heart and blood vessels, including heart attacks and strokes.11
One study published this year found that women with vitamin D levels in the top one-third of the population had 68% lower risk of heart attacks compared with those in the lowest third; men in the top third had a 44% lower risk.12
Conversely, if your vitamin D level is in that lower range, you have a 42% increased risk of dying of cardiovascular disease and a 49 to 64% increased risk of a stroke.13,14 The risk of having clogged coronary arteries (the precursor of a heart attack) is more than doubled for people with vitamin D deficiency (less than 20 ng/mL).15
Why does vitamin D deficiency lead to such a dramatic increase in the risk for having America’s #1 killer disease?
It’s because the heart muscle, blood vessels, and other circulatory system components are rich in vitamin D receptors, which means they depend heavily on vitamin D for optimum function.16
Animals bred to have no vitamin D receptors have cardiovascular disease at an early age and end up with enlarged, dysfunctional hearts.10,17,18 These effects are likely due to vitamin D’s role in increasing protective signaling pathways in those tissues, while preventing harmful ones.19 In addition, vitamin D is required to prevent the excessive buildup of collagen and other fibrotic proteins that stiffen heart muscle and artery walls, reducing blood flow and raising blood pressure.11
Human Studies Verify D’s Heart Benefits
There’s no shortage of compelling human studies of vitamin D and cardiovascular risk. One study found that a daily supplement of 3,320 IU reduced triglycerides by 13.5% (vs. a 3% increase with a standard weight-loss program) and also reduced tumor necrosis factor-alpha, a major marker of inflammation that contributes to atherosclerosis.20 Supplementation has also been shown to relax blood vessels, helping to reduce blood pressure and improve blood flow.19
In a study of African-American teens (a group at very high risk for hypertension and cardiovascular disease), vitamin D supplements of2,000 IU/day boosted blood levels into the sufficient range. The supplemented group also saw a significant and beneficial decrease in aortic stiffness, a measure of cardiovascular risk.21
In another study of African-American adults (also at high risk for cardiovascular disease), 60,000 IU/month for 4 months (about 2,000 IU/day) improved endothelial function, an essential property of blood vessels that allows them to provide adequate blood flow at safe pressures.22 Similar effects have been shown in stroke survivors, who really need to optimize their endothelial function.23
In a study of vitamin D supplementation in obese and overweight women (with an average age of 38 years), supplementing with 1,000 IU/day significantly raised protective HDL-cholesterol levels and significantly lowered body fat mass after 12 weeks.24
Vitamin D deficiency is also implicated in peripheral arterial disease, in which hardened, narrowed arteries fail to provide enough blood to the extremities, especially the legs.25 People with lower vitamin D levels are more likely to develop peripheral artery disease, in direct proportion to how low their levels are. And in fact, amputation, the worst consequence of this condition, is much more likely among those with the lowest levels.25
It’s clearer than ever that you need vitamin D to maintain your cardiovascular health—but it’s important to make sure you’re taking the proper dose. Studies of cardiovascular patients who use only 400 to 600 IU/day in general show no benefits, whereas those using 2,000 IU or more do.20,21,26 One study demonstrated that 2,000 IU/day is the minimum needed to ensure that people reach the minimum target of 30 ng/mL of vitamin D in their blood.27
Vitamin D Lowers Diabetes Risk
Vitamin D can also play a critical role in diabetes. People with diabetes (both types I and II) have even lower levels of vitamin D than the general population.28,29 A vitamin D deficiency makes you 91% more likely to progress to insulin resistance, or “pre-diabetes” (even for those with normal blood sugar). Additionally, a vitamin D deficiency more than doubles your risk for progressing to full-blown type II diabetes.4
This close connection between vitamin D and diabetes is due to vitamin D receptors, which are found in the pancreas’s insulin-producing cells and in liver, fat, and muscle tissue, all of which influence the fate of glucose in your blood.28
For example, white blood cells called macrophages have vitamin D receptors. When macrophages are taken from diabetics, they display a high level of fat content, which contributes to diabetics’ increased cardiovascular risk. However, when those cells are treated in the lab with vitamin D, they stop their pathological fat uptake—ultimately helping reduce cardiovascular risk.30
Similarly, compared to healthy controls, diabetic lab animals have decreased numbers of insulin and vitamin D receptors in their brains; they have more body fat and higher levels of inflammation and DNA damage; and they perform poorly on tests of memory and cognition (remember that Alzheimer’s disease has been called “diabetes of the brain”).31,32 But vitamin D supplementation restored all of those functions to near-normal levels—including improved cognitive performance.31,33 This is an especially important finding, since it shows the potential of vitamin D to help reverse the process of diabetes.
The inflammatory changes in diabetic animals, as in humans, lead to increased fat in the liver, a condition known as non-alcoholic fatty liver disease (NAFLD). This condition further degenerates due to a vitamin D deficiency.34 But when human diabetics with similar elevated inflammatory markers are supplemented with 1,000 IU/day of vitamin D, the inflammation is substantially reduced.35
Perhaps the most remarkable news about vitamin D in this context, however, is that it slows the progression from pre-diabetes to diabetes. When obese, non-diabetic adults supplemented with 2,000 IU/day of vitamin D or placebo for 16 weeks, the vitamin D group had significantly improved glucose clearance from their blood, improved insulin secretion from the pancreas, and a trend to lower levels of hemoglobin A1c (the marker of long-term glucose exposure). Control subjects instead saw a worsening of all those parameters.36
Vitamin D supplementation also benefits those who already have diabetes. Diabetics receiving 1,000 IU/day of vitamin D in yogurt saw significant decreases in fasting blood sugar, hemoglobin A1c, insulin resistance, waist circumference, and body mass index, compared with controls receiving no vitamin D.37
Studies show that supplementation with vitamin D3 can reduce blood pressure, total cholesterol, and LDL-cholesterol—all risk factors for the heart and kidney diseases for which diabetics are at increased risk.38 Treatment with active vitamin D3 also significantly reduces protein levels in urine, a marker of kidney disease.39
With few exceptions, doses of vitamin D of less than 1,200 IU/day have not been shown to be as effective as doses of 2,000 IU/day at lowering blood sugar, hemoglobin A1c, lipid levels, and other disease markers in diabetic patients.40,41


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