Vitamin C for Type 2 Diabetes

No longer recruiting at 1 trial location

Overseen By Ifechukwude C Ebenuwa, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Must be taking: Insulin, Oral hypoglycemics

Disqualifiers: Type 1 diabetes, Microangiopathy, Severe heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether vitamin C can improve blood flow and reduce complications in people with type 2 diabetes. It examines how vitamin C affects red blood cells and blood sugar levels, both with and without supplements. Individuals with type 2 diabetes who manage it with insulin or oral medications and have a hemoglobin A1C of 12% or less might be suitable candidates. Participants will be hospitalized twice to test vitamin C's effects on their red blood cells under different blood sugar conditions. As a Phase 1 trial, this research aims to understand how vitamin C works in people, offering participants the chance to be among the first to explore its potential benefits.

Will I have to stop taking my current medications?

The trial requires that participants stop taking oral hypoglycemic medications when they are admitted to the hospital for the study. Instead, they will be switched to a specific insulin regimen to control blood sugar levels during the trial.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Previous studies have shown that vitamin C supplements are safe for people with type 2 diabetes. Research suggests that taking 500–1000 mg of vitamin C daily can help manage diabetes by lowering blood sugar levels and improving insulin use. This dosage is considered safe and affordable for many with diabetes.

For vitamin E, evidence indicates it might help improve cholesterol levels in people with diabetes. However, studies have not found that vitamin E alone significantly affects blood sugar control. The doses used in these studies are generally considered safe.

Overall, both vitamin C and vitamin E have been well-tolerated in earlier research. These supplement doses carry minimal risks, making them a promising option for further study in diabetes management. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using vitamin C and vitamin E for type 2 diabetes because these vitamins might offer a new way to manage the condition. Unlike standard treatments like metformin or insulin, which focus on controlling blood sugar levels directly, vitamin C and E could reduce oxidative stress, a harmful process that can worsen diabetes. This approach is promising because it targets an underlying issue rather than just the symptoms, potentially improving overall health and making diabetes easier to manage in the long run.

What evidence suggests that vitamin C might be an effective treatment for type 2 diabetes?

Research has shown that vitamin C, which participants in this trial will receive, can help people with type 2 diabetes manage their blood sugar more effectively. Studies have found that it can lower blood sugar levels and enhance insulin use. Vitamin C might also reduce blood fats in people with diabetes. In this trial, participants will also receive vitamin E supplementation. Although vitamin E has not significantly affected blood sugar control in type 2 diabetes, it might improve insulin use in overweight individuals. These findings suggest that vitamin C could be a valuable addition to diabetes management, while the benefits of vitamin E might be more limited. ^{1 2 4 6 7}

Who Is on the Research Team?

Ifechukwude C Ebenuwa, M.D.

Principal Investigator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Are You a Good Fit for This Trial?

Adults aged 18-65 with Type 2 Diabetes, having an HgA1C of <=12% and generally in good health can join this trial. They must be on insulin or oral hypoglycemic agents, have controlled blood pressure, and agree to use contraception if female. Those with mild diseases like hypothyroidism may participate. People with severe illnesses, diabetic complications, or a history of non-compliance are excluded.

Inclusion Criteria

My blood pressure is under control, and I don't have serious heart, kidney, or blood vessel problems.

This is not a criterion, but rather a label for a specific group within the study. More information is needed to understand the screening criteria for Arm 1.

I am willing to use effective birth control methods during the study.

Exclusion Criteria

I have signs of blood vessel damage, like pain while walking, heart issues, stroke, or eye/kidney problems.

I have diabetes with eye problems and need to control my blood sugar to prevent worsening.

Stage 1 and 2: Subjects with clear evidence of non-compliance with protocol/study instructions

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Stage 1 - Inpatient Evaluation

Evaluate the effect of hyperglycemia on vitamin C RBC physiology without supplementation

1 week

1 inpatient visit

Supplementation

Participants receive vitamin C and E supplementation for a minimum of 8 weeks

8 weeks

Biweekly or monthly outpatient visits

Stage 2 - Inpatient Evaluation

Investigate the effect of vitamin C and E supplementation on RBC physiology during euglycemic and hyperglycemic states

1 week

1 inpatient visit

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Vitamin C
• Vitamin E

Trial Overview The study is testing whether Vitamin C supplements can improve the flexibility of red blood cells (RBCs) in people with diabetes by reducing microvascular damage. Participants will undergo two hospital stays for monitoring without and then with Vitamin C supplementation to see if there's any change in RBC rigidity related to their glucose levels.

How Is the Trial Designed?

Group I: Stage 2 Experimental Treatment 2 Interventions

Inpatient admission to NIH CC after at least 8 weeks of vitamin C and vitamin E supplementation. Testing periods include: euglycemic period with serial blood and urine sampling followed by hyperglycemic period (induced with high-carbohydrate diet; diabetic subjects only) with serial blood and urine sampling.

Group II: Stage 1 Experimental Treatment 2 Interventions

Inpatient admission to NIH CC, consisting of euglycemic period with serial blood and urine sampling followed by hyperglycemic period (induced with high-carbohydrate diet; diabetic subjects only) with serial blood and urine sampling.

Who Is Running the Clinical Trial?

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Lead Sponsor

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

A systematic review of 28 studies involving 1,574 participants found that oral vitamin C supplementation significantly reduced systolic blood pressure by an average of 6.27 mmHg and HbA1c levels by 0.54%, indicating potential benefits for glycemic control and cardiovascular health in people with type 2 diabetes.

Despite these promising results, the evidence quality is low to moderate, and most studies were short-term, suggesting that more extensive and longer-term research is needed before vitamin C can be recommended as a standard treatment for type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Vitamin C Supplementation on Glycemic Control and Cardiovascular Risk Factors in People With Type 2 Diabetes: A GRADE-Assessed Systematic Review and Meta-analysis of Randomized Controlled Trials. Mason, SA., Keske, MA., Wadley, GD.[2021]

Individuals with diabetes have a significantly higher prevalence of vitamin C renal leak (33%) compared to nondiabetic controls (9%), indicating a potential issue with vitamin C retention in diabetic patients.

Diabetic participants also exhibited 30% lower mean plasma vitamin C concentrations, and factors such as glycemic control, obesity, and kidney function were found to predict the occurrence of vitamin C renal leak.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abnormal urinary loss of vitamin C in diabetes: prevalence and clinical characteristics of a vitamin C renal leak. Ebenuwa, I., Violet, PC., Padayatty, S., et al.[2023]

In patients with type 2 diabetes, a significant decrease in vitamins C, B2, and beta-carotene levels was observed, indicating a potential nutritional deficiency in this population.

Supplementing with a vitamin-mineral complex (300% of the Recommended Dietary Allowance) for 3 weeks improved levels of vitamins C and beta-carotene and helped maintain B2 levels, suggesting that such supplementation may be beneficial for managing vitamin deficiencies in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Influence of vitamin and mineral complex on clinical and metabolic indexes and vitamin status of patients suffering from type 2 diabetes]. Plotnikova, OA., Sharafetdinov, KhKh., Zykina, VV., et al.[2010]

In a study of 50 type 2 diabetes patients and 50 healthy controls, diabetic patients had significantly lower plasma vitamin C levels (0.22 mg/dL) compared to controls (0.47 mg/dL), despite both groups consuming adequate dietary vitamin C.

The findings suggest that type 2 diabetes may impair the body's ability to utilize vitamin C, indicating a need for diabetic patients to increase their intake of vitamin C-rich foods beyond the standard recommendations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low Plasma Ascorbate Levels in Type 2 Diabetic Patients With Adequate Dietary Vitamin C. Bansal, A., Hadimani, CP.[2021]

In a study involving 8171 female health professionals over a median follow-up of 9.2 years, vitamin C showed a trend towards reducing the risk of developing type 2 diabetes, but this result was not statistically significant.

Vitamin E was associated with a slight increase in diabetes risk, while beta-carotene showed no significant effect on diabetes risk, indicating that these antioxidants may not be effective for diabetes prevention in high-risk women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of vitamins C and E and beta-carotene on the risk of type 2 diabetes in women at high risk of cardiovascular disease: a randomized controlled trial. Song, Y., Cook, NR., Albert, CM., et al.[2023]

In a study of 998 participants with type 2 diabetes, no significant protective association was found between serum levels of ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E) and the development of diabetic retinopathy, suggesting these antioxidants may not play a crucial role in preventing this condition.

The observed associations were influenced by recent supplement use, indicating that dietary antioxidants alone may not be effective in reducing the risk of retinopathy in individuals with diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relations of serum ascorbic acid and alpha-tocopherol to diabetic retinopathy in the Third National Health and Nutrition Examination Survey. Millen, AE., Gruber, M., Klein, R., et al.[2019]

Ascorbate supplementation in diabetic rats restored plasma ascorbate levels and increased other antioxidants like retinol and tocopherol, but did not reduce markers of oxidative stress (MDA and diene conjugates).

High-dose ascorbate supplementation may have both antioxidant and prooxidant effects, suggesting that it should be used cautiously in diabetes management due to potential risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of ascorbate supplementation on oxidative stress in the streptozotocin diabetic rat. Young, IS., Torney, JJ., Trimble, ER.[2022]

People with diabetes mellitus generally have at least 30% lower levels of vitamin C in their blood compared to those without diabetes, suggesting they may have higher dietary needs for this vitamin.

Vitamin C supplementation does not significantly affect blood glucose levels but can lower harmful cellular sorbitol concentrations and reduce capillary fragility, indicating potential benefits for vascular health in diabetics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does diabetes mellitus increase the requirement for vitamin C? Will, JC., Byers, T.[2019]

In a study involving 8 volunteers with type 2 diabetes, different doses of vitamin C significantly increased serum vitamin C levels, but did not show any significant effects on lipid levels or markers of inflammation and coagulation.

The findings suggest that while vitamin C may have potential anti-atherosclerotic effects in diabetic individuals, it does not operate through the conventional pathways typically associated with cardiovascular risk, as measured by established surrogate markers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does short-term vitamin C reduce cardiovascular risk in type 2 diabetes? Gutierrez, AD., Duran-Valdez, E., Robinson, I., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7647560/

Ascorbic acid supplementation in type 2 diabetes mellitus Studies have shown that ascorbic acid supplementation can reduce blood glucose, increase insulin synthesis and secretion, improve insulin resistance.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1871402123001200

The effects of vitamin C supplementation on glycemic ... Several studies have shown that vitamin C supplementation improves glycaemic control in DM patients by lowering plasma glucose levels, HbA1c, food intake, and ...

3. diabetesjournals.org diabetesjournals.org/care/article/44/2/618/35482/Effects-of-Vitamin-C-Supplementation-on-Glycemic

Effects of Vitamin C Supplementation on Glycemic Control and ... Evidence from short-term studies suggests that vitamin C supplementation may improve glycemic control and BP in people with type 2 diabetes.

4. academic.oup.com academic.oup.com/nutritionreviews/advance-article/doi/10.1093/nutrit/nuaf133/8222634

Effects of Vitamin C and/or E Supplementation on Glycemic ... Our data showed that vitamin C may have a greater impact on lowering blood lipids in diabetic individuals, whereas vitamin E showed no evidence ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36526243/

Vitamin C supplementation for diabetes management Oral vitamin C doses of 500-1000 mg per day are potentially effective, safe, and affordable for many individuals with diabetes.

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0891584922010292

Vitamin C supplementation for diabetes management Oral vitamin C doses of 500–1000 mg per day are potentially effective, safe, and affordable for many individuals with diabetes.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT00001870

Study of the Effects of Vitamin C on Patients With Type 2 ... Researchers believe that doses of vitamin C in diabetics or patients with vitamin C deficiency will improve insulin sensitivity and function of endothelium.