Summary:
In obese men, intranasal vitamin C application (80 mg/day for 8 days) significantly improved insulin sensitivity, increased serum vitamin C levels, and attenuated neuroenergetic phosphocreatine (PCr) decline compared to placebo treatment, though it was associated with no reported adverse effects.
| PICO | Description |
|---|---|
| Population | Fifteen obese men (BMI >30 kg/m2) and fifteen normal weight men (BMI 20–25 kg/m2). |
| Intervention | Intranasal administration of vitamin C (80 mg ascorbic acid/day) for 8 consecutive days. |
| Comparison | Placebo administered intranasally under the same protocol. |
| Outcome | In obese participants, vitamin C improved insulin sensitivity acutely (p = 0.003), increased serum vitamin C concentrations (p = 0.011), prevented postprandial vitamin C decline (p ≤ 0.002), and reduced PCr decline (p = 0.008). No significant effect on spontaneous food intake was observed. |
Clinical Context
Obesity is characterized by systemic metabolic dysfunction including insulin resistance, oxidative stress, and alterations in brain energy metabolism. The brain, despite comprising only 2% of body weight, consumes approximately 20% of the body’s glucose supply and is particularly vulnerable to metabolic perturbations. Emerging research has identified impaired cerebral energy homeostasis in obesity, with reduced high-energy phosphate compounds such as phosphocreatine reflecting compromised neuroenergetic status. Vitamin C serves as a critical antioxidant and enzymatic cofactor in the central nervous system, where it achieves concentrations 10-fold higher than in plasma. Individuals with obesity frequently exhibit lower circulating vitamin C levels despite adequate dietary intake, potentially due to increased oxidative consumption. The intranasal delivery route bypasses first-pass metabolism and may provide more direct access to the brain via olfactory and trigeminal pathways. This pilot study explores whether intranasal vitamin C can address obesity-related metabolic and neuroenergetic deficits through a novel delivery mechanism.
Clinical Pearls
- Intranasal vitamin C administration significantly improved insulin sensitivity in obese men after just 8 days of treatment, suggesting rapid metabolic benefits through this novel delivery route.
- Obese participants demonstrated attenuated decline in brain phosphocreatine levels, indicating improved cerebral energy reserve capacity with vitamin C supplementation.
- Serum vitamin C concentrations increased significantly with intranasal administration and were protected from the postprandial decline typically observed in obesity.
- The intervention showed no effect on spontaneous food intake, suggesting the metabolic benefits occur through insulin signaling pathways rather than appetite regulation.
Practical Application
While these findings are preliminary, they suggest that intranasal vitamin C delivery may offer a unique approach to addressing obesity-related metabolic dysfunction. Clinicians should recognize that obese patients often have suboptimal vitamin C status despite apparently adequate dietary intake, and this deficiency may contribute to insulin resistance and impaired brain metabolism. Although intranasal vitamin C formulations are not yet widely available for clinical use, this research highlights the importance of optimizing antioxidant status in obese patients. Standard oral vitamin C supplementation remains reasonable for patients with documented deficiency, though the superior brain penetration achieved through intranasal delivery suggests this route may eventually prove more effective for neurometabolic targets.
Broader Evidence Context
This study builds upon prior research demonstrating lower vitamin C levels in obesity and associations between vitamin C status and insulin sensitivity. The neuroenergetic findings align with growing recognition that obesity affects brain metabolism and function beyond traditional cardiovascular risk factors. Previous work using magnetic resonance spectroscopy has documented altered brain energy metabolism in obesity, and this study extends those observations by demonstrating reversibility with targeted antioxidant intervention. The intranasal delivery approach represents an innovative strategy with precedent in insulin research, where intranasal administration has shown metabolic effects.
Study Limitations
- The sample size of 15 obese and 15 normal-weight participants is small, limiting statistical power and generalizability of findings.
- Only male participants were included, preventing extrapolation of results to women who may have different vitamin C metabolism and obesity phenotypes.
- The 8-day intervention period is brief, and sustained effects with longer treatment duration remain unknown.
- Intranasal vitamin C formulations are not commercially available, limiting immediate clinical translation.
- The study did not assess long-term glycemic control measures such as HbA1c or evaluate clinical outcomes beyond surrogate markers.
Bottom Line
Intranasal vitamin C administration improves insulin sensitivity and attenuates brain energy decline in obese men after just 8 days of treatment. While this novel delivery route shows promise for addressing obesity-related metabolic dysfunction, larger and longer trials are needed before clinical recommendations can be made.
Source: Lena-Christin Ingwersen, et al. “Metabolic and Neuroenergetic Effects of Intranasal Vitamin C Application in the Human Brain.” Read article here.
