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High-dose vitamin E supplementation normalizes retinal blood flow and creatinine clearance in patients with type 1 diabetes.
Abstract
OBJECTIVE: To determine the effectiveness of vitamin E treatment in normalizing retinal blood flow and renal function in patients with <10 years of type 1 diabetes. RESEARCH DESIGN AND METHODS: An 8-month randomized double-masked placebo-controlled crossover trial evaluated 36 type 1 diabetic and 9 nondiabetic subjects. Subjects were randomly assigned to either 1,800 IU vitamin E/day or placebo for 4 months and followed, after treatment crossover, for a further 4 months. Retinal blood flow was measured using video fluorescein angiography, and renal function was assessed using normalized creatinine clearance from timed urine collections. RESULTS: After vitamin E treatment, serum levels of vitamin E were significantly elevated (P<0.01) in both type 1 diabetic and control patients. Hemoglobin A1c was not affected by vitamin E treatment. Diabetic patient baseline retinal blood flow (29.1+/-7.5 pixel2/s) was significantly (P = 0.030) decreased compared with that of nondiabetic subjects (35.2+/-7.2 pixel2/s). After vitamin E treatment, diabetic patient retinal blood flow (34.5+/-7.8 pixel2/s) was significantly increased (P<0.001) and was comparable with that of nondiabetic subjects. Additionally, vitamin E treatment significantly (P = 0.039) normalized elevated baseline creatinine clearance in diabetic patients. CONCLUSIONS: Oral vitamin E treatment appears to be effective in normalizing retinal hemodynamic abnormalities and improving renal function in type 1 diabetic patients of short disease duration without inducing a significant change in glycemic control. This suggests that vitamin E supplementation may provide an additional benefit in reducing the risks for developing diabetic retinopathy or nephropathy.
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“In addition, vitamin E treatment significantly normalized elevated creatinine clearance in patients with diabetes 1.”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Bursell et al. 1999
In the citing paper
“The results have shown that the serum level of vitamin E was significantly increased in both type 1 diabetic and control subjects. Glycated hemoglobin A1c (HbA1c) was improved by the vitamin E supply.”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Bursell et al. 1999
In the citing paper
“Retina blood flow was evaluated using fluorescein angiography and was significantly lower compared to that of non-diabetic subjects. After treatment with vitamin E retina blood flow significantly increased in the group of diabetic patients and reached the level of non-diabetic subjects.”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Bursell et al. 1999
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“Oral administration of vitamin E increases retinal blood flow and normalizes hemodynamic abnormalities in the retina of diabetic patients (Bursell et al., 1999).”
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Marco, E. D., Jha, J. C., Sharma, A., Wilkinson‐Berka, J. L., Jandeleit-Dahm, K. A. M., & de Haan, J. B. (2015) · Clinical Science · doi:10.1042/cs20150093 · Cited by 86
Economides, P. A., Khaodhiar, L., Caselli, A., Caballero, A. E., Keenan, H. A., Bursell, S., King, G. L., Johnstone, M. T., Horton, E. S., & Veves, A. (2005) · Diabetes · doi:10.2337/diabetes.54.1.204 · Cited by 84
“01 Antihypertensive treatment No treatment 46 (53) 23 (72) 23 (40) — -Blockers 3 (3) 0 3 (5) — ACE inhibitors 23 (26) 7 (22) 16 (28) — Diuretics 2 (2) 0 2 (4) — Calcium antagonists 3 (3) 0 3 (5) — Combination 10 (12) 2 (6) 8 (15) — Diabetes treatment Diet 11 (13) — 11 (19) — Oral agents 38 (43) — 38 (67) — Insulin 40…”
ResultSelf-citationVincenzo, A. D., Tana, C., Hadi, H. E., et al. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20205101 · Cited by 83
“[33] 1999 RCT Type 1 diabetes Positive effects on creatinine clearance”
BackgroundMethodA 5-Year Follow-Up of Antioxidant Supplementation in Type 2 Diabetic Retinopathy
García‐Medina, J. J., Pinazo-Duran, M. D., Garcia‐Medina, M., Zanón‐Moreno, V., & Pons-Vázquez, S. (2010) · European Journal of Ophthalmology · doi:10.5301/ejo.2010.6212 · Cited by 87
“cial effects on the development of retinopathy (5-18), but the results from very limited clinical trials are somewhat ambiguous (19-23).”
BackgroundEffects of total glucosides of paeony on oxidative stress in the kidney from diabetic rats
Su, J., Zhang, P., Zhang, J., et al. (2009) · Phytomedicine · doi:10.1016/j.phymed.2009.07.005 · Cited by 83
“While, antioxidant administration has been shown to have potential beneficial effects in the human kidney and experimental diabetes (Craven et al. 1997; Bursell et al. 1999).”
BackgroundNutritional and medical food therapies for diabetic retinopathy
Shi, C., Wang, P., Airen, S., Brown, C. J., Liu, Z., Townsend, J. H., Wang, J., & Jiang, H. (2020) · Eye and Vision · doi:10.1186/s40662-020-00199-y · Cited by 82
“A careful randomized, double-masked, placebo-controlled crossover trial at the Joslin Institute established that for patients with T1DM of fewer than ten years duration, vitamin E supplementation of 1800 IU daily improved retinal blood flow [184].”
Luteolin ameliorates cardiac failure in type I diabetic cardiomyopathy
Wang, G., Li, W., Lu, X., Bao, P., & Zhao, X. (2012) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2012.04.007 · Cited by 80
“On another level, antioxidant administration has been reported to show beneficial effects on parameters of oxidative stress and cardiovascular functions in experimental diabetes (Bursell et al., 1999).”
BackgroundBursell, S., & King, G. L. (1999) · Diabetes Research and Clinical Practice · doi:10.1016/s0168-8227(99)00047-9 · Cited by 80
Self-citationAsbún, J., Manso, A. M., & Villarreal, F. J. (2004) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00340.2004 · Cited by 79
“Our results also support the notion that vitamin E treatment may be a worthwhile consideration for treatment of DM cardiomyopathy as supported by results observed in other organs (10, 20, 49).”
BackgroundResultUpdate on the Treatment of Diabetic Retinopathy
Wilkinson‐Berka, J. L., & Miller, A. G. (2008) · The Scientific World JOURNAL · doi:10.1100/tsw.2008.25 · Cited by 78
“An 8-month clinical trial randomised 36 T1D and nine nondiabetic people to receive either 1,800 IU vitamin E/day or placebo for 4 months, and subjects were then followed, after treatment cross-over, for a further 4 months[188].”
Kowluru, R. A. (2008) · Archives of Ophthalmology · doi:10.1001/archopht.126.9.1266 · Cited by 77
Li, L., & Renier, G. (2006) · Metabolism · doi:10.1016/j.metabol.2006.06.022 · Cited by 74
“Previous studies have shown that administration of antioxidants to diabetic animals prevents the development of retinopathy [42,43] and ameliorates metabolic, hemodynamic, biochemical, and histologic retinal abnormalities that might be relevant to diabetic retinopathy [44-48].”
Background
Metadata
- Authors
- Bursell, S. E., Clermont, A. C., Aiello, L. P., Aiello, L. M., Schlossman, D. K., Feener, E. P., Laffel, L., & King, G. L.
- Affiliations
- Joslin Diabetes Center (US)
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 1999-08-01
- Volume
- 22
- Issue
- 8
- Pages
- 1245-1251
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- OpenAlex
- W2027478328
- Cited by
- 333
- References
- 0
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 6 · 2023: 10 · 2022: 9 · 2021: 3 · 2020: 11 · 2019: 7 · 2018: 7 · 2017: 7 · 2016: 5 · 2015: 6 · 2014: 14 · 2013: 11 · 2012: 16
- FWCI
- 20.09
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes Care (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Keywords
- vitamin E supplementation, type 1 diabetes, retinal blood flow, retinal hemodynamics, creatinine clearance, renal function, diabetic nephropathy, diabetic retinopathy, glycemic control, HbA1c
- MeSH terms
- Adolescent, Adult, Analysis of Variance, Creatinine, Diabetes Mellitus, Type 1, Diabetic Retinopathy, Dose-Response Relationship, Drug, Double-Blind Method, Female, Humans, Male, Metabolic Clearance Rate, Middle Aged, Regional Blood Flow, Retinal Vessels, Vitamin E, Treatment Outcome, Plasminogen Activator Inhibitor 1, Cross-Over Studies, Dietary Supplements
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