Has science proven that the minimal acceptable blood level of vitamin D, in the form of 25(OH)D, is above 50 ng/mL (125 nmol/L)? No. If you’ve been trying to maintain your levels this high because you thought this was the case, I’m sorry to break the news. There is, on the contrary, good evidence that 25(OH)D levels should be at least 30-35 ng/mL (75-88 nmol/L). Much higher levels may be better, or they could start causing harm, especially in the absence of adequate vitamins A and K2. Once we leave the land of 30-35 ng/mL, however, we enter the land of speculation.
The idea that science has proven we need to maintain 50 ng/mL as a minimum comes from Dr. John Cannell of the Vitamin D Council. In his article “Am I Vitamin D Deficient?” he writes the following:
Thanks to Bruce Hollis, Robert Heaney, Neil Binkley, and others, we now know the minimal acceptable level. It is 50 ng/ml (125 nmol/L). In a recent study, Heaney, et al expanded on Bruce Hollis’s seminal work by analyzing five studies in which both the parent compound (cholecalciferol) and 25(OH)D levels were measured. They found that the body does not reliably begin storing cholecalciferol in fat and muscle tissue until 25(OH)D levels get above 50 ng/ml (125 nmol/L). The average person starts to store cholecalciferol at 40 ng/ml (100 nmol/L), but at 50 ng/ml (125 nmol/L) virtually everyone begins to store it for future use. That is, at levels below 50 ng/ml (125 nmol/L), the body uses up vitamin D as fast as you can make it, or take it, indicating chronic substrate starvation—not a good thing. 25(OH)D levels should be between 50–80 ng/ml (125–200 nmol/L), year-round.
There are a few problems with this argument. To begin with, Drs. Hollis, Heaney, Binkley, and the other authors of this study rightly made very different conclusions from their own data. In the report they wrote for the American Journal of Clinical Nutrition, they wrote the following:
One could plausibly postulate that the point at which hepatic 25(OH)D production becomes zero-order [this is the point at which the enzymes converting vitamin D to 25(OH)D are saturated with vitamin D – CM] constitutes the definition of the low end of normal status. This value, as suggested from the equation in Figure 3 , is at a serum 25(OH)D concentration of 88 nmol/L (35.2 ng/mL) (the y-axis intercept of the linear portion of the equation in Figure 3 ). It is interesting that this estimate is very close to that produced by previous attempts to define the lower end of the normal range from the relations of serum 25(OH)D to calcium absorption (29) and to serum parathyroid hormone concentration (ie, 75–85 nmol/L, or 30–34 ng/mL) (30).
According to the authors of this study, then, the point at which the vitamin D enzymes are saturated and vitamin D “accumulates within the body, both in serum and probably in body fat” is not 40 or 50 ng/mL (100 or 125 nmol/L) but rather 35 ng/mL (88 nmol/L).
The authors used a statistical approach that pooled together data from several studies. They presented most of their data in Figure 4, and the data from one other study in Figure 5. They did not determine the point at which vitamin D starts getting stored in body fat in particular individuals. On the contrary, they used a statistical approach to infer the point at which this occurs in their entire study population. Now, if you compare Figures 4 and 5, looking for the point at which the slope of the line dramatically changes, you will see that it changes at a higher level of 25(OH)D in Figure 5. Dr. Cannell seems to have used the data from Figure 5 to say when vitamin D gets stored in body fat in “virtually everyone” as opposed to “the average person,” but in fact the authors stated that they did not use the data from Figure 5 to determine this point because a different and apparently inferior method of measuring vitamin D levels was used in that data set.
So, we are back to the authors’ original conclusions, that vitamin D saturates its activation enzymes and starts getting stored in body fat when 25(OH)D levels reach 35 ng/mL (88 nmol/L).
The second problem is that this study does not “prove” or “show” or “demonstrate” what the optimal or minimal blood level of vitamin D is. The authors state that one could plausibly postulate that the minimum acceptable blood level is the point at which the enzymes are saturated and vitamin D is stored in body fat, but they never state that “we now know the minimal acceptable level.”
The most definitive way to determine the ideal 25(OH)D level would be to conduct a randomized, controlled trial with different levels of vitamin D supplementation targeted at reaching specific blood levels of 25(OH)D and to test the effects of the different levels of supplementation on clinical outcomes, such as bone mineral density, fracture rate, insulin resistance, glucose tolerance, cancer, or heart disease.
We do not yet have this type of data. We do, however, have some strong support for raising 25(OH)D levels to at least 35 ng/mL (88 nmol/L). For example, as the authors of the study we have been looking at pointed out, similar attempts to use statistical approaches to define the 25(OH)D level that maximizes calcium absorption, maximally suppresses parathyroid hormone (which leaches calcium from bone), or maximizes bone mineral density have suggested similar results. A recent randomized, placebo-controlled trial showed that supplementing insulin-resistant women with 4,000 IU of vitamin D per day for six months reduced insulin resistance and had the most powerful effect in women whose 25(OH)D level was raised to over 32 ng/mL (80 nmol/L).
What about higher levels? The evidence is conflicting, and some of it indicates possible harm. For example, a study in the American Journal of Medicine published in 2004 found that in Americans aged over 50, the maximal bone mineral density (BMD) occurs around 32-40 ng/mL (80-100 nmol/L). Among Mexican Americans, BMD continues to rise a little after this point, but for whites it plateaus and begins dropping off around 45 ng/mL (110 nmol/L) and for blacks it begins dropping off even before 40 ng/mL (100 nmol/L).
If 50 ng/mL (125 nmol/L) is our minimal acceptable level, this study would seem to suggest that those of us who have “acceptable” levels of 25(OH)D would have lower bone mineral density than those of us who are moderately deficient. And that just doesn’t make sense.
Another study published in the European Journal of Epidemiology in 2001found that South Indians with 25(OH)D levels higher than 89 ng/mL (223 nmol/L) were three times more likely to have suffered from ischemic heart disease than those with lower levels – and of course with such a dramatic elevation of heart disease risk, the risk may have begun increasing at levels substantially lower than 89 ng/mL.
Neither of these studies were designed to show that high levels of 25(OH)D cause decreases in bone mineral density or increases in heart disease risk, but it is possible. As I especially emphasized in my Wise Traditions and Medical Hypotheses articles on vitamin K2, bone resorption and blood vessel calcification are prominent symptoms of vitamin D toxicity in animal experiments. I also emphasized the role of vitamins A and K2 in protecting against vitamin D toxicity. So, even if these levels are in fact harmful, they may only be harmful or may be primarily harmful in the absence of adequate vitamins A and K2. The presence of the other fat-soluble vitamins could even turn these levels from harmful to beneficial.
Nevertheless, what we need in order to show that levels higher than 50 ng/mL are helpful or harmful are vitamin D supplementation trials comparing the effect of different doses that result in different blood levels on clinical health outcomes, and similar studies examining the interactions between vitamin D and the other fat-soluble vitamins.
Lifeguards in the tropics can reach blood levels in the 50’s and 60’s naturally from sun exposure, suggesting these levels are “natural,” although lifeguards in Israel have 20 times the rate of kidney stones as the general population. Kidney stones may be the most sensitive indicator of vitamin D toxicity and are a symptom of vitamin A and K2 deficiency. Thus, I suspect these levels are healthful in the context of a diet rich in vitamins A and K2, and if my levels were to reach this high in the summer sun while I were eating such a diet I certainly would not worry.
But if you are trying desperately to maintain year-round 25(OH)D status between 50-80 ng/mL using vitamin D supplements, you have entered the land of speculation. Enter at your own risk.