I have always recommended a 25(OH)D level between 40 and 80 ng/ml, or about in the middle of the reference range (30-100 ng/ml). The traditional reason the reference range goes up to 100 ng/ml is because sunbathers and lifeguards occasionally have such levels. To my knowledge, the highest recorded 25(OH)D level from sun exposure alone is from a pregnant free-living hunter-gatherer in modern day Tanzania whose level was 105 ng/ml.
Now evidence exists that levels above 60 ng/ml may be harmful. First author Dr Karin Amrein, of the Medical University of Graz in Austria, studied 90 day mortality in more than 24,000 patients admitted to one of two Boston teaching hospitals between the years 1993 and 2011.
Amrein K, Quraishi SA, Litonjua AA, Gibbons FK, Pieber TR, Camargo CA Jr, Giovannucci E, Christopher KB. Evidence for a U-shaped relationship between pre-hospital vitamin D status and mortality: a cohort study. J Clin Endocrinol Metab. 2014 Jan 13:jc20133481.
The authors separated the patients (average age 61) into seven categories of 25(OH)D levels. The lowest was < 10 ng/ml and the highest was > 70 ng/ml with every 10 ng/ml increment in between. Then they compared the 25(OH)D levels to 90 day mortality. The lowest odds ratio of dying was .94, which was seen in those with 25(OH)D levels between 50-60 ng/ml. However, those with levels below 30 ng/ml and above 60 ng/ml had a statistically significant increased risk of dying in 90 days.
Of the 24,000 patients, 390 (1.6% of total sample) had 25(OH)D levels between 60 and 70 ng/ml and 299 patients (1.2% of the total sample) had levels above 70 ng/ml. Patients with these two levels had odds ratios of dying in 90 days of 1.5 and 1.7, respectively. Of course, those with levels below 30 ng/ml also had an increased risk of dying.
Eight percent of the 390 patients with levels between 60 and 70 ng/ml died and 8% with levels above 70 ng/ml died in 90 days. The lowest death rate (5%) was in those with levels between 30 and 60 ng/ml. The highest death rate (10%) was in those with levels <10 ng/ml.
Unfortunately, the source of the vitamin D necessary to get levels above 60 ng/ml was not identified. Through most of those years it had to come from one of three sources: the sun, prescription ergocalciferol, or cod liver oil. During the majority of those years, vitamin D3 supplements were only available in 400 IU preparations, not enough to explain levels above 60 ng/ml. Food cannot get levels above 60 ng/ml unless one eats reindeer meat, seagull eggs, lichen and whale blubber.
There was a seasonal difference in those with high levels, but it does not look like enough sun was obtained to explain those high levels. The season of blood draw’s influence was not different for those with levels between 60 and 70 ng/ml and only slightly different for those with levels above 70 ng/ml. So sunshine cannot explain the high levels.
That means the patients with high levels during most of those years were probably either taking prescription ergocalciferol for osteoporosis or a cod liver oil supplement. Readers know about the potential problems with cod liver oil and its high vitamin A content.
What about ergocalciferol? A recent subgroup analysis of the most recent Cochrane meta-analysis of randomized controlled trials and mortality suggested that vitamin D2 may increase mortality.
Bjelakovic G, Gluud LL, Nikolova D, Whitfield K, Wetterslev J, Simonetti RG, Bjelakovic M, Gluud C. Vitamin D supplementation for prevention of mortality in adults. Cochrane Database Syst Rev. 2014 Jan 10;1:CD007470.
So in all likelihood, these patients were either using cod liver oil or taking prescription ergocalciferol, both of which may be dangerous.