Here's the short answer: On limited evidence, it appears that Vitamin D supplements are best absorbed if taken with the largest meal of the day.
There haven't been many studies on the mechanisms of Vitamin D absorption, so the evidence one way or the other is somewhat limited. However, there are two studies that can give us confidence in taking Vitamin D with a meal.
First, two clinicians at the Cleveland Clinic decided to look into this very question in 2010. They assumed that since Vitamin D is a fat-soluble vitamin, it would be best absorbed through the intestines by hitching a ride along with fat absorption.
We commonly find that patients take the medication on an empty stomach or with a light meal. Because vitamin D is fat soluble, we hypothesized that absorption would be improved if patients were instructed to take their supplement (same dose, same preparation) with their largest meal of the day.
The clinicians also found that the type of Vitamin D pill did not matter: liquid capsule and solid tablet were both well-absorbed. This finding has been repeated in other studies.
Their conclusions in their own words:
At present, there are few studies that provide convincing evidence for the optimal method for taking vitamin D supplements. Admittedly, there are several limits to our study, including the small sample size, lack of a control group, and an inability to know exactly how the patients took their supplements. Despite these limitations, the results are striking and consistent across a rather heterogeneous group of patients (i.e., different disease states and different preparations and doses of vitamin D). It therefore seems reasonable to ask patients to take vitamin D supplements with their largest meal because it may be a cost-effective strategy that could very well help patients to achieve optimal serum levels of 25(OH)D.
Second, an Israeli study from 1992 noted that iron deficiency causes fat malabsorption problems, and, by logical extension, fat-soluble vitamins. The researchers were attempting to find out whether additional iron supplementation would boost fat absorption and fat-soluble vitamin absorption (like Vitamins A, D, E, and K).
Severe iron-deficiency anemia may cause malabsorption syndrome. Our assumption was that mild iron-deficiency anemia may impair fat absorption including vitamin D, which is fat soluble, and hence decrease vitamin D concentrations in the plasma. If this assumption is correct, treatment with iron will correct the anemia and will also improve the absorption of vitamin D and increase its concentration in the plasma...
These studies indicate that vitamins and minerals interact in our digestive tract, boosting each other's absorption rates. This means that when vitamins and minerals are allowed to interact, as when we take supplementation with meals, increased absorption is possible. In fact, it is well-known that Vitamin D is necessary for the absorption of calcium. It has also been suggested that the types of fat in the food may affect Vitamin D absorption, as well.
Our digestive tract is a wonderfully tuned system that dances to a complex rhythm of receptors and cells. The intestines are designed to extract nutrients from whole foods, so it would seem to make sense that supplement absorption would best occur in the context of a meal. In fact, one nutritionist suggests that even water-soluble vitamins like the B vitamins and Vitamin C should be taken with a meal.
However, there are some contradictory statements available. For example, a 2010 article in the Canadian online magazine The Globe and Mail quoted a doctor as saying, "Take [Vitamin D] on a full stomach, take it on an empty stomach. Take it once a day, take it twice a day. Take it with fat, take it without fat. None of that matters." The same doctor runs a Vitamin D website which essentially makes the same claim without reference to evidence.
Ultimately, I was unable to find any guidelines which recommended taking Vitamin D between meals. So I will rely on the available research, which appears to indicate that Vitamin D supplementation is best absorbed if taken with the largest meal of the day.
If you know of a study which recommends taking Vitamin D between meals, please leave a comment or contact me.