The statement by the IOM that skeletal health can be maintained at serum 25(OH)D levels of 20 ng/ml is incorrect. 30 ng/ml should be looked at as the lower end of the acceptable range for bone health. There have been randomized controlled trials showing major reductions in fractures by getting the serum level to 29 ng/ml. Fracture reduction does not reliably occur at levels less than 30 ng/ml and in some cases as high as 40 ng/ml. Osteoid seam width, a measure of vitamin D deficiency, only reaches normal values when the level is above 30 ng/ml. There is significant evidence above the IOM panel’s “adequate” level of 20 ng/ml.

Robert P. Heaney, M.D.
Creighton University Medical Center, Suite 4841
Omaha, NE 68131
Tel: (402) 280 4029
Fax: (402) 280 4751

Heike Bischoff-Ferrari and Walter Willett

Comment on the IOM recommendations released on November 30th 2010[1]: For adult bone health, low on Vitamin D and generous on Calcium

Most evidence on vitamin D and calcium is available for bone health. Thus the recommendations of the IOM panel are largely based on bone health and call for 600 IUs vitamin D daily for all ages up to age 70 and 800 IUs after age 71. This assumes that most people get little sun exposure. The panel raised the safe upper limit of 2000 IU daily to 4000 IUs for adults, and declares a safe upper limit of 1000 to 3000 IU per day in children depending on their age. According to the IOM, serum concentrations of 50 nmol/l is sufficient for 97% of the population, including bone health as the main endpoint.

While the IOM recommendation of an increase in vitamin D intake is supported by the available data from double-blind RCTs of fracture risk, a threshold of 50 nmol/l for its 25(OH)D blood level is not. In two 2009 meta-analyses of double-blind RCTs, a threshold of 50 nmol/l was insufficient for fracture or fall reduction based on achieved 25(OH)D levels in the treatment groups[2, 3]. Also, in the very large population-based NHANES analysis, bone density increased with higher 25(OH)D levels far beyond 50 nmol/l in younger and older adults suggesting that the IOM threshold recommendation is too low for optimal bone health in adults[4]. In contrast to the IOM report, the IOF recommended in their 2010 position paper on vitamin D a threshold of 75 nmol/l for optimal fall and fracture reduction and recommended 800 to 1000 IU vitamin D per day for seniors age 60 years and older[5].

With the IOM recommendation of 600 to 800 IU vitamin D, most healthy adults will reach 50 nmol/l 25(OH)D but not optimal bone health with respect to hip bone density or fracture reduction. Despite evidence from several double-blind RCTs and a meta-analysis summarizing these data[3], the IOM report concluded that there is inconsistent evidence on vitamin D and fall prevention. In contrast to the IOM report, the evidence of the effect of vitamin D supplementation at a dose of 700 to 1000 IU vitamin D per day on fall reduction was acknowledged by the 2010 IOF position paper on vitamin D[5].

Although benefits of serum concentrations of 25(OH)D higher than 50 nmol/l on endpoints other than bone health have not been documented by randomized trials, the evidence for benefit is quite strong for some, especially colorectal cancer[6]. The IOM conclusion that intakes of vitamin D are adequate for most of the US population assumes that lack of randomized trials means lack of benefit, which seems illogical. At a minimum, the conclusion should indicate uncertainty about benefit of higher intakes and blood levels. In support of a greater safety margin in research and supplementation strategies, the IOM doubled the safe upper limit from 2000 IU to 4000 IU vitamin D per day, which is appropriate.

The new recommendations of the IOM call for a calcium intake from all sources ranging from 700 milligrams for children aged 1 to 3 up to 1,200 milligrams for women 51 and older. Compared to the last IOM report, calcium recommendations remained largely the same with a small reduction for men age 50 to 70 to 1,000 from 1,200 milligrams per day. The panel confirms a safe upper limit of 2000 to 3000 mg calcium per day for adults.

The calcium recommendations in different age groups are largely based on calcium balance studies lasting only 7 to 12 days, which is likely to be misleading with respect to long term calcium needs. Less data is available to substantiate recommendations with respect to clinical endpoints including bone density and fracture reduction. Notably, in the large population-based NHANES study, there was no overall relation between intake of calcium and hip bone density. Only at 25(OH)D levels below 50 nmol/l, a greater calcium intake was associated with hip bone density among women[7]. Further, in two meta-analyses of randomized trials of calcium supplements alone compared with placebo there was no significant effect on fracture risk[8, 9]. Notably, however, in one meta-analysis of 4 double-blind RCTs an adverse effect of calcium supplementation at a dose between 1000 and 1200 mg per day on hip fracture risk could not be excluded and no dose-response relation between dietary calcium intake and risk of hip fractures was documented in a meta-analysis of large cohort studies[9].

Further, the apparent lack of benefit for high calcium intake on bone density increase or fracture reduction together with recent data on the possible adverse effects of calcium supplements on cardiovascular health[10] and nephrolitiasis[11], may make the IOM safe upper limit for calcium intake appear too high. We note that the WHO has suggested that 500 mg of calcium per day is an adequate intake.

Finally, the IOM states that more data regarding the interaction of vitamin D and calcium on bone health are needed and no recommendation was provided on their combination.

Notably, several data suggest that vitamin D increases calcium absorption[12] and that a higher intake of calcium beyond 800 mg per day may not contribute to PTH suppression[13] and hip bone density[7] if 25(OH)D levels are above 40 to 50 nmol/l. In the trials that tested vitamin D plus calcium for fracture reduction confounding by calcium intake cannot be completely eliminated, but two observations are important: (1) in one 2009 meta-analysis of double-blind RCTs, fracture reduction was the same for the main effect of vitamin D and trials that combined vitamin D with calcium if the adherence-adjusted vitamin D dose was more than 480 IU per day[2]; (2) calcium supplementation by itself did not reduce risk of fractures [9]. As noted in the IOM review, in the analysis of NHANES data with more than 9000 subjects, calcium intake was associated with hip bone density only among women with low 25(OH)D levels; in all other groups there was no relation between calcium intake and bone density. In contrast, 25(OH)D levels were consistently and positively associated with hip bone density[7]. Thus, with adequate 25(OH)D levels or sufficient vitamin D intake, higher calcium intakes may not be correlated with bone health. Thus, calcium recommendations could be downward adjusted with vitamin D supplementation – possibly also for safety reasons. This has not been considered by the IOM report.

Prof. Heike A. Bischoff-Ferrari, MD, DrPH
Director, Centre on Aging and Mobility, University of Zurich
SNF-Professor Dept. of Rheumatology, University Hospital Zurich
Gloriastrasse 15
8091 Zurich
Switzerland

Prof. Walter C. Willett, MD, DrPH
Chair, Department of Nutrition
Fredrick John Stare Professor of Epidemiology and Nutrition
Department of Nutrition
Department of Epidemiology
651 Huntington Avenue
Building II Room 311
Boston, Massachusetts 02115
USA

IOM: Dietary Reference Intakes for Calcium and Vitamin D. http://www.iom.edu/Reports/2010/Dietary-Reference-Intakes-for-Calcium-and-Vitamin-D.aspx 2010.
Bischoff-Ferrari HA, Willett WC, Wong JB, et al.: Prevention of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials. Arch Intern Med 2009; 169(6): 551-61.
Bischoff-Ferrari HA, Dawson-Hughes B, Staehelin HB, et al.: Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials. Bmj 2009; 339: b3692.
Bischoff-Ferrari HA, Dietrich T, Orav EJ, Dawson-Hughes B: Positive association between 25-hydroxy vitamin D levels and bone mineral density: a population-based study of younger and older adults. Am J Med 2004; 116(9): 634-9.
Dawson-Hughes B, Mithal A, Bonjour JP, et al.: IOF position statement: vitamin D recommendations for older adults. Osteoporos Int.
Giovannucci E: Epidemiological evidence for vitamin D and colorectal cancer. J Bone Miner Res 2007; 22 Suppl 2: V81-5.
Bischoff-Ferrari HA, Kiel DP, Dawson-Hughes B, et al.: Dietary calcium and serum 25-hydroxyvitamin D status in relation to BMD among U.S. adults. J Bone Miner Res 2009; 24(5): 935-42.
Tang BM, Eslick GD, Nowson C, Smith C, Bensoussan A: Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis. Lancet 2007; 370(9588): 657-66.
Bischoff-Ferrari HA, Dawson-Hughes B, Baron JA, et al.: Calcium intake and hip fracture risk in men and women: a meta-analysis of prospective cohort studies and randomized controlled trials. Am J Clin Nutr 2007; 86(6): 1780-90.
Bolland MJ, Avenell A, Baron JA, et al.: Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ; 341: c3691.
Jackson RD, LaCroix AZ, Gass M, et al.: Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 2006; 354(7): 669-83.
Heaney RP, Dowell MS, Hale CA, Bendich A: Calcium absorption varies within the reference range for serum 25-hydroxyvitamin D. J Am Coll Nutr 2003; 22(2): 142-6.

New IOM vitamin D recommendations – baby steps and missteps

In late November 2010, the Institute of Medicine (IOM) released its new guidelines for vitamin D and calcium, updating them from 1997. While the recommendations for calcium intake showed little change, the recommendations for vitamin D were modestly increased — yet not nearly as much as the burgeoning research in vitamin D warrants. Unfortunately, even this incremental progress was undermined by the IOM’s misguided assertion that the minimum serum vitamin D level should be lowered.

At the Center for Better Bones and the Better Bones Foundation, we realize these guidelines attempt to establish values for basic nutritional “adequacy” (meeting the basic needs of 97–98% of the population), not optimum nutrient intake. The news is good in some ways and not so good in others. We see the current IOM adjustment to the vitamin D Dietary Reference Intake (DRI) as representing both baby steps forward and detrimental missteps.

Take two baby steps forward

1. Raising the Recommended Daily Allowances

» Tripling the RDA for individuals age 1 to 70, from 200 IU to 600 IU

» Doubling the RDA for those 71 and older, from 400 IU to 800 IU

» Doubling the recommendation for infants from birth to 1 year, from 200 IU to 400 IU per day
Raising the RDAs for all age groups is a step in the right direction. However, the new amounts recommended are still in most cases far less than those needed to reach an optimum, health-promoting vitamin D status.

2. Raising the “Tolerable Upper Limits”

» Doubling the Upper Limit (UL) for individuals age 9 and older, from 2000 IU to 4000 IU per day

» Setting the UL for infants 0 to 6 months at 1000 IU; 6-12 months at 1500 IU; children 1-3 years at 2500 IU; and children 4-8 years at 3000 IU per day

Raising the Tolerable Upper Level Intake (the highest average daily intake likely to pose no risk of adverse effects to almost everyone in the population) moves us forward and confirms the safety of 4000 IU vitamin D for the population as a whole. While this is an incremental step forward, preeminent vitamin D researchers worldwide find ample evidence for a UL of 8000–10,000 IU. Furthermore, many people have such low vitamin D levels that they need more than 4000 IU daily to restore and maintain adequate vitamin D reserves.

As an anthropologist giving these Upper Level guidelines consideration, I find it interesting to note that healthy adults utilize approximately 3000–4000 IU of vitamin D every day,¹ and that we have an enormous capacity to produce vitamin D upon sunlight exposure. For example, in 20 minutes on a sunny beach an average fair-skinned adult can produce at least 10,000 IU of vitamin D² (dark-skinned people take longer to produce the same amount).

Now for the IOM’s missteps

1. Establishing 20 ng/mL as “the level that is needed for good bone health for practically all individuals”

We at the Center for Better Bones find this conclusion to be erroneous, and submit that the minimal serum level 25(OH)D level conducive to bone health is on the order of 30–32 ng/mL. Our assertion is substantiated by a number of clinical trials, as discussed in our 2008 vitamin D fracture studies review,³ as well as various meta-analyses. In 2009, for example, Bischoff–Ferrari and colleagues published two separate meta-analyses documenting that 20 ng/mL was not sufficient for either fracture⁴ or fall reduction.⁵

As noted osteoporosis researcher Dr. Robert Heaney recently commented, “Fracture reduction does not reliably occur at levels less than 30 ng/mL and in some cases as high as 40 ng/mL. Osteoid seam width, a measure of vitamin D deficiency, only reaches normal values when the level is above 30 ng/mL.”⁶ Finally, it is of note that both the International Osteoporosis Foundation⁷ and Osteoporosis Canada⁸ support 30 ng/mL as the target level for bone health.

2. Basing the vitamin D intake guidelines solely upon the bone health benefits of vitamin D

In their review of the scientific studies the IOM panel concluded that the evidence supported a role for vitamin D exclusively in bone health. The vast body of new research supporting the health benefits of vitamin D for a reduction in the incidence of various cancers, cardiovascular disease, hypertension, diabetes, metabolic syndrome, falls, immune response, autoimmune disease, and the like were deemed inconclusive and unreliable. Thus, the IOM panel chose to base its new vitamin D reference intake solely on their evaluation of the role that vitamin D plays in bone health.

This is an unfortunate misstep for several reasons. Most importantly, it flies in the face of mounting documentation of multiple, life-supporting health benefits of higher vitamin D levels. A colorful graphic representation of these data (see www.grassrootshealth.net) has been compiled by distinguished vitamin D scientists Drs. Cedric Garland and Carole Baggerly.

Secondly, dismissing the new non-bone vitamin D research allowed the IOM to set a much lower apparent level of adequacy. Numerous studies on cancers, heart disease, diabetes, multiple sclerosis, and other diseases clearly indicate that vitamin D levels higher than the minimum required for basic bone health are needed. In fact, a panel of 41 expert vitamin D researchers and medical practitioners has set the evidence-based vitamin D target level at 40–60 ng/mL.⁹ We at the Center for Better Bones concur with the target level.

3. Concluding that with a few exceptions all North Americans are receiving enough vitamin D and need no additional supplementation

Only by setting a very low level for vitamin D adequacy (20 ng/mL) could the IOM make this statement. Vitamin D levels in this country are well below the therapeutic target set by major vitamin D researchers (40–60 ng/mL), and they are declining. According to the NHANES national survey the average vitamin D level has dropped, from 30 ng/mL in 1988–1994 to 24 ng/mL in 2001–2004. The percentage of those below 10 ng/mL has increased from 2% to 6%, and the percentage with levels of 30 or above has decreased from 45% to 23%.¹⁰

Moving forward — don’t wait another decade for the IOM to catch up

We evolved in abundant sunlight: Our genetic coding reflects the longstanding importance of vitamin D, with nearly 2800 binding sites for the vitamin D receptor across the length of our genome. Further, vitamin D is documented to influence the expression of some 229 genes,¹¹ and the emerging research links higher levels of vitamin D with reduced incidence of numerous diseases. Obtaining a vitamin D level of 40–60 ng/mL would approximate that of our ancestors and — not coincidentally — levels associated with protection from today’s most problematic health issues.¹² Obtaining this more “natural” vitamin D blood level is easy and safe to do — simply have your vitamin D level tested and then supplement with appropriate vitamin D3 (or sunlight) to reach the target 40–60 ng/mL level.

Finally, knowledge is power. If you are concerned about maximizing your health and enhancing disease-free longevity you might want to keep abreast of the leading-edge vitamin D research. One easy way to do this is to keep in touch with public-interest vitamin D advocacy groups at Grassroots Health (www.grassrootshealth.net) and the Vitamin D Council (www.vitamindcouncil.org). It’s your health and your life. You could wait another decade for the IOM to seriously review the new scientific findings of vitamin D, or you can move forward by raising your awareness and drawing your own conclusions!

Susan E. Brown, Ph.D.
Director
The Center for Better Bones
The Better Bones Foundation

¹ Heaney, R.P. et al. 2003. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am. J. Clin. Nutr., 77 (1), 204-201. URL: http://www.ajcn.org/content/77/1/204.full (accessed 12.08.2010).

² [No author or date of publication listed.] Understanding vitamin D cholecalciferol. URL: http://www.vitamindcouncil.org/ (accessed 12.08.2010).

³Brown, S.E. 2008. Vitamin D and fracture reduction: An evaluation of the existing research. Alt. Med. Rev., 13 (1), 21-33. URL: http://www.thorne.com/altmedrev/.fulltext/13/1/21.pdf accessed 12.08.2010).

⁴Bischoff-Ferrari, H.A., Willett, W.C., et al. 2009. Prevention of nonvertebral fractures with oral vitamin D and dose dependency: A meta-analysis of randomized controlled trials. Arch. Intern. Med., 169(6), 551–561. URL: http://archinte.ama-assn.org/cgi/content/full/169/6/551 (accessed 12.08.2010).

⁵ Bischoff-Ferrari, H.A., Dawson-Hughes, B., et al. 2009. Fall prevention with supplemental and active forms of vitamin D: A meta-analysis of randomized controlled trials. BMJ, 339, b3692. URL: http://www.bmj.com/content/339/bmj.b3692.full (accessed 12.08.2010).

⁶ Heaney, R., 2010. As quoted at “Grassroots Health. Vitamin D action — IOM Bone Health.” URL: http://www.grassrootshealth.net/iombonehealth (accessed 12.08.2010).

⁷ Dawson-Hughes, B., et al. 2010. IOF position statement: Vitamin D recommendations for older adults. Osteoporos. Int., 21 (7), 1151–1154. URL: http://www.springerlink.com/content/nn0577u6826418w7 (accessed 12.08.2010).

⁸ Papaioannou, A., et al. 2010. Clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: Summary. CMAJ, 182 (17), 1864–1873. http://canadianmedicaljournal.ca/cgi/content/full/182/17/1864 (accessed 12.08.2010).

⁹ Baggerly, C. 2010. Grassroots Health | Vitamin D action – GRH Recommendations. URL: http:// grassrootshealth.net/recommendation (accessed 12.08.2010).

¹⁰ Adit, A., et al. 2009. Demographic differences and trends of vitamin D insufficiency in the US population, 1988-2004. Arch. Intern. Med., 169 (6), 626–632. URL: http://archinte.ama-assn.org/cgi/content/full/169/6/626 (accessed 12.08.2010).

¹¹ Ramagopalan, S., et al. 2010. A ChIP-seq defined genome-wide map of vitamin D receptor binding: Associations with disease and evolution. Genome Res., 20 (10), 1352–1360. URL; http://genome.cshlp.org/content/20/10/1352.long (accessed 09.01.2010).

¹² Vieth, R. 2001.Would prehistoric human 25-hydroxyvitamin D concentrations be beneficial, and how much vitamin D do we need to ensure desirable nutritional targets? In Nutritional Aspects of Osteoporosis, eds. P. Burckardt, et al. San Diego: Academic Press.