Analysis linking higher vitamin D intake to reduced type 1 diabetes risk affirms prior indications; lab study finds vitamin A and fruity antioxidants protective
by Craig Weatherby
Young children who consume substantial amounts of omega-3s from fish and/or fish oil appear less likely to develop type 1 diabetes.
Now, the results of an evidence review suggest that vitamin D—another nutrient that's abundant only in fatty fish—may help deter this lifelong disease.
Humans also make vitamin D in response to UVB sunrays, and historically, this has been our species' primary source of this long overlooked, hormone-like nutrient, whose myraid roles are only beginning to be uncovered.
But few modern Americans (or Europeans) get enough sun year-round to ensure adequate blood levels. This is why leading university researchers recommend raising the US RDA from 400 IU to 1,000 or 2,000 IU, and urge everyone to take vitamin D supplements and eat fatty fish.
What is type 1 diabetes?
Type 1 diabetes is an autoimmune condition that affects more than 750,000 Americans. It usually happens in early childhood but can occur in young adulthood.
It occurs when the immune system mounts an inflammatory attack on insulin-producing beta cells in the pancreas, using special immune-system proteins.
This autoimmune attack destroys the body's ability to make insulin, so type 1 diabetes patients require frequent insulin injections to control blood sugar.
About half of cases occur in people with genetic profiles that predispose them develop some form of autoimmunity, but genetic factors alone do not seem to cause type 1 diabetes.
Instead, type 1 diabetes seems to require an environmental trigger. The chief suspects are certain viruses, especially the group B coxsackieviruses (Drescher KM, Tracy SM 2008; Atassi MZ, Casali P 2008).
Regions on viral proteins can resemble regions on bodily proteins, and this can lead the immune system to attack both at once.
Another suspected cause is a disruption in the levels or activity of immune-system proteins, including TNF-alpha, which is involved in chronic inflammation and autoimmunity. (In the mouse study reported below—see “Vitamin A and food-borne antioxidants”—both of these food factors suppressed TNF-alpha and the risk of diabetes.)
(Type 2 or “adult onset” diabetes is not an autoimmune disease. It has strong genetic components that interact with lifestyle factors, generally begins in mid-life or later, and can often be managed with weight control, prudent diets, and various drugs. Fish and their omega-3s may also be helpful: search our newsletter archive for “diabetes”.)
Vitamin D and type I diabetes risk
It appears that vitamin D—which, like omega-3s, is abundant only in fatty seafood—may help prevent or ameliorate the severity of type 1 diabetes.
This hormone-like nutrient regulates the immune system in ways that remain poorly understood.
Vitamin D acts through a receptor on cell membranes, and the results of worldwide studies link several different genetic variations in this receptor to increased risk of type 1 diabetes.
Children with type 1 diabetes tend to have low vitamin D levels, and, as the authors of a recent review article wrote, “Optimal vitamin D supplementation during early life has been shown to be protective” (Soltesz G et al. 2007).
(For more on the links between vitamin D and other autoimmune conditions, see “Vitamin D vs. Multiple Sclerosis” and “ ”)
In a paper published this month, leading vitamin D investigator William B. Grant, Ph.D. proposed a highly plausible hypothesis to explain—at least in part—why vitamin D might help prevent type 1 diabetes (Grant WB 2008).
He noted that several autoimmune diseases—including multiple sclerosis and type 1 diabetes—are linked to viral infections, which increase during winter when vitamin D production from sun exposure is at its lowest level of the year.
Vitamin D stimulates production of bodily compounds that fight bacterial and viral infections effectively, so Dr. Grant suggests that vitamin D may reduce the risk of several autoimmune diseases by inhibiting viral infections or reducing their severity.
Evidence review detects benefit from dietary vitamin D
To further explore the strong indications of links between type 1 diabetes and vitamin D insufficiency, a pair of British scientists analyzed data collected in four case-control studies and one cohort study.
(In cohort studies, researchers follow a group of people over a period of years, recording their diets, lifestyle, and health outcomes. In case-control studies, researchers compare the diets and lifestyle habits of people with a disease such as type 1 diabetes to the habits of healthy people.)
In total, the authors of the new evidence review analyzed data on 6,455 infants.
The results indicated that infants who received vitamin D supplements were 29 percent less likely to develop type 1 diabetes, compared with infants who received no vitamin D supplements (Zipitis CS, Akobeng AK 2008).
In addition, the analysis showed some evidence of a “dose-response” effect. In other words, the children who received the highest doses of vitamin D were at lowest risk of developing type 1 diabetes.
Vitamin A and food-borne antioxidants protect mice from type I diabetes
USDA researchers used mice to test the separate effects of vitamin A and antioxidant-rich grape powder (Zunino SJ et al. 2007).
The USDA scientists already know that vitamin A and food-borne antioxidants—such as the polyphenols abundant in the freeze-dried grape powder also tested in the study—can regulate the immune system.
But no one had ever tested the ability of either vitamin A or grape powder to suppress type 1 diabetes in animals or humans.
Physiologist Charles B. Stephensen collaborated with molecular biologist Susan J. Zunino for an investigation conducted at the USDA's Agricultural Research Service (ARS) Nutrition Research Center in Davis, California.
They fed 45 mice a diet known to induce type 1 diabetes, but some were also given either grape powder or high doses of vitamin A.
After about seven months, only 25 percent of the mice given vitamin A and only 33 percent of those given grape powder had developed diabetes, compared with 71 percent of the other mice.
The researches also found that the mice fed vitamin A or grape powder had significantly lower levels of TNF-alpha. As noted above, this is one of the immune-system proteins associated with onset of type 1 diabetes.
As Stephensen and Zunino wrote, “Increasing polyphenol or vitamin A levels in the diet may have profound effects on suppressing inflammatory immune cells and reducing the oxidative damage in the islets that contributes to loss of beta cells… dietary interventions such as those in this study may by useful for treatment of other autoimmune and inflammatory diseases.”
- Atassi MZ, Casali P. Molecular mechanisms of autoimmunity. Autoimmunity. 2008 Mar;41(2):123-32. Review.
- Bailey R, Cooper JD, Zeitels L, Smyth DJ, Yang JH, Walker NM, Hyppönen E, Dunger DB, Ramos-Lopez E, Badenhoop K, Nejentsev S, Todd JA. Association of the vitamin D metabolism gene CYP27B1 with type 1 diabetes. Diabetes. 2007 Oct;56(10):2616-21. Epub 2007 Jul 2.
- Boraska V, Skrabic V, Zeggini E, Groves CJ, Buljubasic M, Peruzovic M, Zemunik T. Family-based analysis of vitamin D receptor gene polymorphisms and type 1 diabetes in the population of South Croatia. J Hum Genet. 2008;53(3):210-4. Epub 2007 Dec 27. PMID: 18161000 [PubMed - in process]9: Related Articles, LinksMimbacas A, Trujillo J, Gascue C, Javiel G, Cardoso H. Prevalence of vitamin D receptor gene polymorphism in a Uruguayan population and its relation to type 1 diabetes mellitus. Genet Mol Res. 2007 Sep 5;6(3):534-42.
- Drescher KM, Tracy SM. The CVB and etiology of type 1 diabetes. Curr Top Microbiol Immunol. 2008;323:259-74.
- Ginanjar E, Sumariyono, Setiati S, Setiyohadi B. Vitamin D and autoimmune disease. Acta Med Indones. 2007 Jul-Sep;39(3):133-41. Review.
- Grant WB. Hypothesis-Ultraviolet-B Irradiance and Vitamin D Reduce the Risk of Viral Infections and thus Their Sequelae, Including Autoimmune Diseases and some Cancers. Photochem Photobiol. 2008 Mar-Apr;84(2):356-65. Epub 2008 Jan 7.
- Greer RM, Rogers MA, Bowling FG, Buntain HM, Harris M, Leong GM, Cotterill AM. Australian children and adolescents with type 1 diabetes have low vitamin D levels. Med J Aust. 2007 Jul 2;187(1):59-60.
- Jørgensen SP, Bartels LE, Agnholt J, Glerup H, Nielsen SL, Hvas CL, Dahlerup JF. [Vitamin D insufficiency--possible etiologic factor of autoimmune diseases] Ugeskr Laeger. 2007 Oct 22;169(43):3655-60. Review. Danish.
- Lu J, Dixon WT, Tsin AT, Basu TK. The metabolic availability of vitamin A is decreased at the onset of diabetes in BB rats. J Nutr. 2000 Aug;130(8):1958-62.
- Ramos-Lopez E, Brück P, Jansen T, Herwig J, Badenhoop K. CYP2R1 (vitamin D 25-hydroxylase) gene is associated with susceptibility to type 1 diabetes and vitamin D levels in Germans. Diabetes Metab Res Rev. 2007 Nov;23(8):631-6.
- Soltesz G, Patterson CC, Dahlquist G; EURODIAB Study Group. Worldwide childhood type 1 diabetes incidence--what can we learn from epidemiology? Pediatr Diabetes. 2007 Oct;8 Suppl 6:6-14.
- Zipitis CS, Akobeng AK. Vitamin D Supplementation in Early Childhood and Risk of Type 1 Diabetes: a Systematic Review and Meta-analysis. Arch Dis Child. 2008 Mar 13; [Epub ahead of print]
- Zunino SJ, Storms DH, Stephensen CB. Diets rich in polyphenols and vitamin A inhibit the development of type I autoimmune diabetes in nonobese diabetic mice. J Nutr. 2007 May;137(5):1216-21.