Vitamin C for Insulin Resistance

Recruiting in Palo Alto (17 mi)

Overseen by Seth Holwerda, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: University of Kansas Medical Center

Must not be taking: Statins, Antihypertensives

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

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing if Vitamin C can improve blood vessel health and lower blood pressure in obese adults who have difficulty processing sugar. These individuals often have high blood pressure and a higher risk of heart disease. Vitamin C might help by making blood vessels healthier and calming the nerves that control them. Vitamin C has been studied for its potential benefits in reducing blood pressure and improving heart health, though results have been inconsistent.

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.

What data supports the effectiveness of the treatment Vitamin C for insulin resistance?

Research suggests that Vitamin C, an antioxidant, may help improve insulin resistance by reducing inflammation and improving glucose uptake in cells. Studies have shown that Vitamin C deficiency can worsen insulin resistance, while supplementation may help improve metabolic disorders. ^{1 2 3 4 5}

Is Vitamin C safe for humans?

Vitamin C is generally considered safe for humans, but taking very high doses might affect how your body handles sugar, as seen in a study where a large amount of Vitamin C delayed the body's insulin response to sugar intake. ^{1 2 5 6 7}

How does the treatment Vitamin C differ from other treatments for insulin resistance?

Vitamin C is unique in treating insulin resistance because it acts as an antioxidant, reducing oxidative stress and inflammation, which are key factors in insulin resistance. Unlike some other treatments, it can improve insulin sensitivity by targeting these underlying issues, and it is administered orally as a simple vitamin supplement. ^{1 2 5 6 8}

Research Team

Seth Holwerda, PhD

Principal Investigator

University of Kansas Medical Center

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Ascorbic acid (Vitamin)

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.

Participant Groups

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 Canada for the following indications:

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+

Dr. Steve Stites

University of Kansas Medical Center

Chief Executive Officer

MD from University of Kansas School of Medicine

Dr. Matthias Salathe

University of Kansas Medical Center

Chief Medical Officer

MD from University of Kansas School of Medicine

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. Mexico pubmed.ncbi.nlm.nih.gov

[Effect of oral administration of ascorbic acid on insulin sensitivity and lipid profile in obese individuals]. [2013]

2. England pubmed.ncbi.nlm.nih.gov

Effect of vitamins C and E on insulin resistance in diabetes: a meta-analysis study. [2022]

3. Switzerland 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. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Does diabetes mellitus increase the requirement for vitamin C? [2019]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Vitamin C deficiency aggravates tumor necrosis factor α-induced insulin resistance. [2018]

6. United States 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. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Megadose of vitamin C delays insulin response to a glucose challenge in normoglycemic adults. [2018]

8. Canada pubmed.ncbi.nlm.nih.gov

Ascorbic acid reduces insulin resistance and pancreatic steatosis by regulating adipocyte hypertrophy in obese ovariectomized mice. [2023]