Vitamin C for Insulin Resistance

Overseen By Manuel Clark, MPA

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Kansas Medical Center

Must not be taking: Statins, Antihypertensives

Disqualifiers: Diabetes, Hyperlipidemia, Hypertension, Heart disease, others

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 2 hours

23 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to explore how Vitamin C (ascorbic acid) might improve blood vessel function and lower blood pressure in obese adults with insulin resistance. Researchers seek to determine if Vitamin C can prevent hypertension and reduce the risk of heart disease. The trial includes two groups: one receiving a Vitamin C infusion and the other a placebo (a harmless sugar solution with no effect). Ideal participants are obese individuals with insulin resistance who do not currently have high blood pressure or heart disease. As a Phase 1 and Phase 2 trial, this research focuses on understanding Vitamin C's effects and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking health insights.

Will I have to stop taking my current medications?

The trial requires that you stop taking any vitamin C or E supplements or omega-3 fatty acids starting 2 weeks before joining. If you are currently taking statins or antihypertension medications, you cannot participate in the trial.

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

Research shows that Vitamin C, also known as ascorbic acid, is generally safe for use. Studies involving people with type 2 diabetes have found that Vitamin C helps control blood sugar levels and improves insulin use. These studies often use high doses of Vitamin C for extended periods without major safety issues.

This trial examines how Vitamin C affects blood pressure by improving blood vessel health in adults with insulin resistance. Previous research suggests that Vitamin C can help manage blood pressure, indicating its safety and effectiveness in this area.

While specific safety data for this trial is not yet available, the extensive use of Vitamin C in other studies supports its safe use. This background should reassure participants considering joining the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard treatments for insulin resistance, such as metformin or lifestyle changes like diet and exercise, the study treatment uses ascorbic acid, also known as vitamin C. Researchers are excited about using ascorbic acid because it may target oxidative stress, a factor in insulin resistance, in a novel way. This approach is different because it leverages the antioxidant properties of vitamin C, and it's administered intravenously, potentially allowing for faster and more direct effects on the body. This method could offer a new, complementary option for managing insulin resistance.

What evidence suggests that ascorbic acid might be an effective treatment for insulin resistance?

Studies have shown that vitamin C can help reduce insulin resistance, a condition where the body doesn't respond well to insulin, the hormone that controls blood sugar. Some research has found that taking vitamin C can lower blood sugar levels and improve insulin function. Another study suggested that vitamin C might also help lower blood pressure, which is important because people with insulin resistance are more likely to develop high blood pressure. This trial will compare an ascorbic acid infusion with a placebo infusion to evaluate its effects on blood vessel health in people with insulin resistance. These findings suggest that vitamin C might be helpful in managing conditions related to insulin resistance. ^{1 2 3 5 6}

Who Is on the Research Team?

Seth Holwerda, PhD

Principal Investigator

University of Kansas Medical Center

Are You a Good Fit for This Trial?

This trial is for obese adults aged 35-65 with insulin resistance. Participants must not be taking statins, antihypertension meds, or have a history of heart or vascular disease. They should stop vitamin C/E and omega-3 supplements two weeks before the study.

Inclusion Criteria

I am willing to stop taking vitamin C, E, or omega-3 supplements 2 weeks before.

Able and willing to provide written informed consent

You are very overweight, with a BMI over 30.

Exclusion Criteria

I am currently on medication for high cholesterol or high blood pressure.

I have a history of vascular disease.

I have a history of heart disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either a placebo or ascorbic acid infusion to assess the impact on blood vessel function and blood pressure

2 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ascorbic acid

Trial Overview

The study tests how well Vitamin C (ascorbic acid solution) can improve blood vessel function in comparison to saline in people with insulin resistance. It aims to see if Vitamin C can lower high blood pressure by improving vascular health.

How Is the Trial Designed?

Group I: Ascorbic acid infusion Active Control 1 Intervention

Ascorbic acid solution (American Regent Laboratories Inc.) will be obtained from the KU Investigational Pharmacy located in the University of Kansas (KU) Clinical Research Center where studies will take place. A priming bolus of 0.06 g ascorbic acid/kg fat free mass (FFM) dissolved in 100 mL of saline will be infused intravenously at 5 mL/min for 20 minutes, followed immediately by a "drip-infusion" of 0.02 g/kg FFM dissolved in 30 mL of saline administered over 2 hours at 0.5 mL/min.

Group II: Placebo infusion Placebo Group 1 Intervention

Saline will be administered over 2 hours

Ascorbic acid is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Vitamin C for:

• Scurvy
• Dietary supplement

Approved in European Union as Vitamin C for:

• Scurvy
• Dietary supplement

Approved in Canada as Vitamin C for:

• Scurvy
• Dietary supplement

Who Is Running the Clinical Trial?

University of Kansas Medical Center

Lead Sponsor

Trials

527

Recruited

181,000+

Published Research Related to This Trial

A systematic review of 14 randomized controlled trials involving 735 patients with type 2 diabetes found that neither vitamin C nor vitamin E supplementation significantly improved insulin resistance, as measured by the HOMA index.

The study concluded that taking vitamin C, vitamin E, or their combination does not enhance insulin resistance in individuals with type 2 diabetes, indicating that these supplements may not be effective for this purpose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of vitamins C and E on insulin resistance in diabetes: a meta-analysis study. Khodaeian, M., Tabatabaei-Malazy, O., Qorbani, M., et al.[2022]

Ascorbic acid (AA) supplementation showed a significant reduction in fasting blood sugar (FBS) levels in type 2 diabetes patients based on a meta-analysis of 5 randomized controlled trials, indicating potential short-term benefits.

However, there is insufficient evidence regarding the long-term safety and efficacy of AA for managing diabetes, and the effect on glycated hemoglobin (HbA1c) was not significant, suggesting caution in recommending long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of ascorbic acid supplementation on type 2 diabetes mellitus in observational and randomized controlled trials; a systematic review with meta-analysis. Tabatabaei-Malazy, O., Nikfar, S., Larijani, B., et al.[2022]

In a study involving nine healthy young adults, a megadose of ascorbic acid (2 g/d) was found to significantly elevate plasma glucose levels one hour after consuming glucose, compared to a placebo.

The presence of high levels of ascorbic acid also altered the insulin response, delaying its peak and prolonging post-meal high blood sugar, likely due to ascorbic acid interfering with glucose uptake in pancreatic beta cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Megadose of vitamin C delays insulin response to a glucose challenge in normoglycemic adults. Johnston, CS., Yen, MF.[2018]

In a study involving high-fat diet-induced obese ovariectomized mice, ascorbic acid (5% in diet for 18 weeks) significantly reduced the size of visceral adipocytes without affecting overall body weight, indicating its potential to combat adipocyte hypertrophy.

Ascorbic acid treatment improved insulin resistance and reduced pancreatic triglyceride accumulation, suggesting it may help manage metabolic issues associated with obesity by decreasing inflammation in adipose tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ascorbic acid reduces insulin resistance and pancreatic steatosis by regulating adipocyte hypertrophy in obese ovariectomized mice. Jeon, S., Lee, J., Shin, Y., et al.[2023]

Vitamin C deficiency worsens insulin resistance caused by TNF-α, as shown in a study using Gulo-/- mice, leading to poorer glucose tolerance and increased liver inflammation.

Supplementing with vitamin C can reverse insulin resistance in liver cells by enhancing glucose uptake and activating key signaling pathways, suggesting it may be a beneficial treatment for metabolic disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin C deficiency aggravates tumor necrosis factor α-induced insulin resistance. Qing, Z., Xiao-Hui, W., Xi-Mei, W., et al.[2018]

In a study involving 16 obese male volunteers, a daily oral supplement of 1 g of ascorbic acid (AA) for four weeks did not lead to significant changes in lipid profiles or insulin sensitivity compared to a placebo group.

The results indicate that ascorbic acid supplementation may not be effective in improving metabolic health markers in obese individuals, as no significant differences were observed before and after the intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of oral administration of ascorbic acid on insulin sensitivity and lipid profile in obese individuals]. Martínez-Abundis, E., Pascoe-González, S., González-Ortiz, M., et al.[2013]

Oral supplementation of ascorbic acid (AA) significantly improved insulin-mediated glucose disposal and increased insulin sensitivity in people with type 2 diabetes, based on a randomized cross-over study lasting four months.

AA supplementation also reduced oxidative stress in skeletal muscle during hyperinsulinaemia, suggesting it could be an effective and affordable adjunct therapy for managing insulin resistance in type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ascorbic acid supplementation improves skeletal muscle oxidative stress and insulin sensitivity in people with type 2 diabetes: Findings of a randomized controlled study. Mason, SA., Della Gatta, PA., Snow, RJ., et al.[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]

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 ...

These findings suggest that long-term (≥12 weeks) and high-dose vitamin C supplementation (≥1000 mg/d) may ameliorate glycemic profile in T2DM patients.

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 ...

Data were extracted for changes in outcomes between vitamin C and control groups. ... vitamin C reduced lipid peroxidation and insulin resistance ...

4.

frontiersin.org

frontiersin.org/journals/nutrition/articles/10.3389/fnut.2021.728880/full

Vitamin C and Metabolic Syndrome: A Meta-Analysis ...

Current evidence suggests that both dietary and circulating vitamin C level is inversely associated with MetS.

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11742600/

Effects of water-soluble vitamins on glycemic control and ...

The findings suggest that vitamin C supplementation can improve glycemic control in type 2 diabetes, as indicated by reduced FBG and HbA1c.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11047647/

A High Vitamin C Micronutrient Supplement Is Unable to ...

Overall, 12-week micronutrient supplementation was unable to mitigate systemic inflammation in people with metabolic syndrome but may improve ...