Vitamin D’s Role in Diabetes
Reconsiderations in Light of New Guidelines and Recent Research
The “sunshine vitamin”, vitamin D (VitD), has captured the attention of healthcare professionals, researchers, and the health-conscious public for much of the last decade. Research has linked low VitD status to many diverse conditions, including osteoporosis, depression, cancer, heart disease, and diabetes, and the topic has been a focus of two past Complementary Corner articles: Vitamin D and Diabetes: No Bones About It, and Vitamin D Update - The Support Continues, because of the evidence suggesting an important role for VitD in pancreatic function and thus diabetes. Based on this evidence (and in response to the frenzy of patient interest), many healthcare providers began regularly ordering blood tests for VitD deficiency [using a test called 25-hydroxycholecalciferol (25-OHD)], and some prescribing very high doses) to replace VitD. At times, the recommended doses were in excess of 10-50 times higher than those recommended by previous guidelines.
However, in 2010 healthcare providers, insurance companies and specialty societies realized that VitD status was being “screened” routinely in practice as a preventive effort and the public was taking large doses of the “sunshine vitamin” as dietary supplements without initial testing. In general, testing and VitD replacement strategies were getting a little out of hand for the still-limited state of the science on optimal VitD replacement methods clinically and there remained a lack of evidence regarding whether or not replacing VitD makes a difference in disease outcomes, including diabetes and heart disease.
To address these issues, the Institute of Medicine (IOM) (the medical division of the U.S. National Academy of Sciences) formed a committee that sought to explore all of the research about how critical VitD may be for general health, and charged them with creating guidelines around minimum dosages, blood testing, and long-term safety. They found very little evidence to support the massive doses prescribed.
What did the IOM learn?
At a length of over 1100 pages, the IOM reviewed thousands of scientific papers related to VitD’s effects on the human body including everything from test tube and animal studies, observations from the population, and clinical trials.1 To examine the evidence, the reviewers divided the literature into several condition-focused sections, which included lengthy discussion of VitD’s relationship to diabetes and cardiovascular conditions. [The IOM study also independently examined calcium (the mineral primarily associated with VitD) but that is perhaps a topic for another article.]
Very broadly, they found strong observational associations between low levels of VitD and higher rates of diabetes and cardiovascular disease. They found very few clinical trials looking at the effects of VitD supplementation on those disease processes, and those studies weren’t consistently positive. In other words, people with low blood levels of VitD clearly had more disease, but giving people with these diseases VitD didn’t consistently help.
The chief concern of the study was to determine based on the available literature whether there was a need to change the daily recommended intake (DRI) for the whole population. On the topic of diabetes, the IOM notes “the evidence in support of a role for VitD as a modulator of pancreatic endocrine function…is not conclusive and therefore is not sufficient to support glucose tolerance as an indicator for DRI development.” They similarly found that they “could not draw an inference about the efficacy of [VitD for cardiovascular disease] to support DRI development.”
On the topic of diabetes, they regularly found a correlation between low 25-OHD levels and diabetes, but did not find evidence of causation. In observing large numbers of people, those with diabetes were more likely to have low 25-OHD levels, but it was unclear what the nature of the relationship was. Because vitamin D can be stored in fat and because people with type-II diabetes often have excessive body fat it may be that VitD has nothing to do with diabetes and the association is only true because the excess fat is holding onto VitD.
Similarly, because VitD levels might represent a marker for the amount of time one spends outdoors (which is itself considered a marker for physical activity), associations between VitD and diabetes or cardiovascular disease might merely represent a finding that more physically active individuals have better overall health. In other words, they didn’t find enough evidence that vitamin D levels so strongly affect the development of diabetes, heart disease, or related conditions that they could confidently recommend increasing the DRI for vitamin D based on these conditions.
The IOM’s conclusions
Because of the rationale outlined above strong associations without a clear understanding of causality, and no clear evidence of benefit from supplementation the IOM refrained from dramatically changing recommendations around the DRI for vitamin D. Their final recommendations suggest a daily intake of 600 IU is sufficient for adults (800 IU for those over 70 years), but an upper limit of 4000 IU was probably safe. They defined serum 25-OHD values of 20 ng/mL (or 50 nmol/L) as sufficient for most people, and stated there is insufficient evidence of safety at serum 25-OHD values higher than 50 ng/mL.
The IOM also recommended continued research on the topic, including research evaluating the safety of higher doses of VitD, experimental clinical trials of VitD replacement in high risk conditions like diabetes, and research evaluating the outcomes in the general population from routine “preventive” screening and replacement.
Research since IOM recommendations
Since the IOM report, a handful of small clinical trials have been published, specifically looking at how VitD supplementation (particulary a form called Vitamin D3 (VitD3), which is the form most commonly supplemented) may impact blood sugar regulation. These trials offer additional insight into the relationship between VitD and diabetes, but are still limited in their findings:
A trial of 92 adults found that 2,000 IU of VitD3 for 16 weeks led to significant improvements in insulin secretion, but minimal (and non-significant) improvements in hemoglobin A1c (HbA1c).2
A 12-week trial of 90 adults found that compared a standard yogurt drink, a yogurt drink fortified with either VitD3 (500 IU) or VitD3 and calcium (500 IU/250mg) resulted in greater improvements in HbA1c, fasting blood sugar, HOMA-IR (a measure of insulin resistance), waist circumference, and other measurements associated with glucose metabolism disorders. Changes in 25 -OHD status were directly correlated with improvements in blood sugar, HOMA-IR, and fat mass.3
A four-week trial of VitD3 supplementation found no improvements in glucose tolerance in 28 patients with type-II diabetes.4
Weight loss of 10% of body weight over 20 weeks led to improved 25-OHD levels, as well as improvements in HOMA-IR and lipid levels. Age-matched non-obese controls had higher levels of 25-OHD at the beginning of the study.5 This study suggests the low 25-OHD status observed in people with diabetes may represent increased fat storage of the vitamin.
Single injections of either 100,000 IU or 200,000 IU of VitD3 showed no improvement in insulin resistance or HbA1c at 16 weeks. These doses are equivalent to about 900 IU/day or 1800 IU/day respectively.6
As the above clinical trials highlight, we still have mixed evidence of whether VitD supplementation may help someone improve their cardiovascular health and/or blood sugar (at the same time, there is really no evidence that VitD insufficiency is good for you!).
Endocrine Society guidelines
Rising to the need for guidance in a confusing clinical area, the Endocrine Society recently released their recommendations for VitD testing, replacement and optimal status.7 Briefly, their guideline suggests:
Using 25-hydroxycholecalciferol (25-OHD) blood testing in patients at risk for deficiency.
25-OHD status <20ng/ml be labeled “deficiency”
25-OHD status 21-29 ng/ml be labeled “insufficiency”
25-OHD status >30 100 ng/ml be labeled “sufficiency”
25-OHD concentrations between 30-100 ng/ml be a therapeutic target for replacing VITD
Age-specific dietary intake of VitD should be:
Children 0-1 year: 400 IU/day
Children 1-18 years: 600 IU/day
Adults 19-50 years: 600 IU/day
Adults 50-70 years: 600 IU/day
Adults >70 years: 800 IU/day
They also state that intake up to 1000 IU/day may be required in children and intake up to 1500-2000 IU/day may be required for adults to maintain VitD sufficiency, i.e., blood concentrations >30 ng/ml.
Final comments - for now
We have just finished our clinical trial, supported by Diabetes Action, to test three types of VitD3 dietary supplements to replace VitD3 status. We are working on publishing our results, which although will not answer all of the many questions about VitD, our study will provide some new insight on the relative effectiveness of three types of VitD3 supplements, add to the literature on the safety of higher VitD3 doses (we used 10,000 IU/day in our study) and also contribute another potential VitD replacement strategy to correct VitD insufficiency. We look forward to describing the results in a future article. In the meantime, because of the new IOM recommendations, many insurance companies are now putting strict limits on payment for VitD blood testing typically restricting payment to conditions such as chronic kidney disease, calcium metabolism disorders, or osteoporosis and related bone conditions. Few insurance companies are including cardiovascular conditions and diabetes in their definitions of “medically necessary” indications for VitD testing.
Unfortunately, this position is in conflict with the recent Endocrine Society recommendation to test those individuals at risk for VitD insufficiency, which would include many older people with cardiovascular disease and diabetes).
On the one hand getting tested for VitD seems like a good idea. However, the test costs between $60 and $90, and multiple tests are often ordered during treatment to ensure sufficiency status is reached. Thus the costs of testing could accumulate to several hundred dollars. One can also buy a lot of time in the gym and extra organic vegetables for the cost of four $90 tests in a year. So how do you balance wanting to be proactive about your health, not wanting to pay lots of money for a test your insurance company does not want to cover, and yet not wanting to take a supplement that you may not need? A few options follow, ranked from cheapest (but least safe) to most expensive (but also most safe):
Take 600-2000 IU VitD3 per day, depending on your age, in food and supplements, without checking your VitD status.
Consult with a nutritionist or naturopathic doctor about your sun exposure and dietary intake of VitD (or search for one of many online tools to help measure your own intake based on a several day diet diary) and assess your own need for a supplement based on your diet.
Ask your naturopathic doctor, nurse practitioner or conventional doctor for a single blood test to determine your status so your need for a supplement, and potential dosing requirements for supplementation can be safely recommended. It may be worth the cost to know for sure as it could save you the need for a supplement at all. Consider testing once per year, though we recommend at least one test before starting any supplementation regimen. If you don’t have a health care provider, find a naturopathic doctor near you at: www.naturopathic.org
Decide it‘s worth it to you to know your status for certain, and commit to at least two tests per year. We would recommend testing in late Fall or early Winter and again in late Spring or early Summer. Typically VitD status drops in the Winter and picks up again in Spring, so supplements may not be needed all year.
We hope this article helps reduce the confusion around the “sunshine vitamin” and offers you some practical advice about how to move forward with your decisions on the need for vitamin D testing and replacement. As more and more research is coming out every day on this topic, we will try to keep you updated on the state of the science, and how new findings may impact your health decisions.
In health, Ryan Bradley, ND, MPH and Bill Walter, ND
1. Dietary Reference Intakes for Calcium and Vitamin D, (The National Academies Press, Washington DC, 2010).
2. Mitri, J., Dawson-Hughes, B., Hu, F.B. & Pittas, A.G. Effects of vitamin D and calcium supplementation on pancreatic beta cell function, insulin sensitivity, and glycemia in adults at high risk of diabetes: the Calcium and Vitamin D for Diabetes Mellitus (CaDDM) randomized controlled trial. Am J Clin Nutr 94, 486-494 (2011).
3. Nikooyeh, B., et al. Daily consumption of vitamin D- or vitamin D + calcium-fortified yogurt drink improved glycemic control in patients with type 2 diabetes: a randomized clinical trial. Am J Clin Nutr 93, 764-771 (2011).
4. Parekh, D., et al. Pilot study to evaluate the effect of short-term improvement in vitamin D status on glucose tolerance in patients with type 2 diabetes mellitus. Endocr Pract 16, 600-608 (2010).
5. Tzotzas, T., et al. Rising serum 25-hydroxy-vitamin D levels after weight loss in obese women correlate with improvement in insulin resistance. J Clin Endocrinol Metab 95, 4251-4257 (2010).
6. Witham, M.D., et al. The effect of different doses of vitamin D(3) on markers of vascular health in patients with type 2 diabetes: a randomised controlled trial. Diabetologia 53, 2112-2119 (2010).
7. Holick, M.F., et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 96, 1911-1930 (2011).