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The potential impact of blood sugar levels on immune function

The potential impact of blood sugar levels on immune function .jpg
Citrus flavonoids may address multiple aspects of health that could influence the immune system directly and indirectly.

Managing immune health is more than taking a multivitamin and continuing through the day. Yes, it helps, but the immune system is much more complex than that. Lately, discussions around the immune system tend to settle on maintaining a healthy gut or proper inflammation response. These are vital elements of a strong immune system, but unfortunately, this complex network of cells, tissues and organs is susceptible to debilitation when the body suffers from particular health challenges. One underestimated and rarely discussed challenge that can impair the immune system is prediabetes.

According to CDC, approximately a third of the U.S. population is prediabetic, but more than 84% of those people are unaware that they have it. Part of the reason could be that although prediabetes constitutes higher-than-normal blood sugar levels, they are not high enough to be diagnosed as type 2 diabetes, and symptoms usually go unnoticed. If not addressed, prediabetes typically develops into type 2 diabetes.

The connection between blood sugar and immune health

Consumers know type 2 diabetes is something to avoid, but they may not realize a key reason to maintain proper blood sugar levels is that it can help support a proper immune defense. Adults with type 2 diabetes have lower natural killer (NK) cell activity compared to those with lower blood sugar levels.1 And high blood sugar affects the immune system in multiple ways, such as impairing white blood cell function. At the same time, the increase in sugar can potentially create an imbalanced microbiome with increased “bad” bacteria compared to normal glucose groups.2

But type 2 diabetes isn’t when immune health complications begin. They start as the body begins to develop insulin resistance with the onset of prediabetes. Stanford researchers studying the effects of prediabetes on immune health found that immune function may be significantly impaired.3 This happens because higher blood sugar levels cause an imbalance of cytokines that provide vital aid in immune cell signaling. These researchers were also able to see higher proportions of the bacteria Blautia in insulin-resistant participants, leading to further sugar misregulation and the worsening of the prediabetic condition.

Research into the relationship between blood sugar levels and the immune system has solidified the negative effect previously discussed on cytokine production and immune cell function.4 The cytokines that play key protective roles against pathogens and for adaptive immune response were being suppressed, thereby also suppressing the body’s immune defense. T cells and leukocyte production was reduced, and neutrophils and macrophages debilitated, leaving the body open to attack and to exacerbating potential health complications.

Fortunately, prediabetes is not the end of the road. Affected persons can often turn their situation around and reduce blood sugar levels, which may result in improved immune health as well. The American Diabetes Association (ADA) recommends taking simple steps toward improving diet and exercise to help lower blood sugar. Research has shown supplementing with citrus flavonoids may help boost these efforts; in fact, the ingredient has shown numerous potential effects through multiple mechanisms.

Overproduction of proinflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha is not only a sign of a dysfunctional immune system, but also a consequence of rising blood sugar levels. If not kept in check, the excess will then exacerbate the situation by worsening insulin resistance. As such, many people with type 2 diabetes are at higher risk of additional health complications, as well as being more susceptible to infectious diseases.4,5

Citrus flavonoids are able to play a role in providing natural support toward a balanced inflammatory response by activating PPARg expression and inhibiting nuclear factor kappa light chain enhancer of activated B cells.6 Lemon flavonoids have also shown that the process to balance the inflammatory response helps increase adiponectin, which is key to normalizing blood sugar levels.7,8 Examples of flavonoids found in lemons include eriocitrin, hesperidin and naringin.

Citrus flavonoids have long been recognized for their synergy with vitamin C, making them popular for use in multivitamins. Plus, research has shown that citrus flavonoids are able to deliver potent antioxidant support.9 By increasing antioxidant capacity, these flavonoids are able to support the body’s efforts to capture free radicals and reduce oxidative stress, which also causes an associated reduction of lipid peroxidation, helping influence a reduction in blood sugar levels.8 By delivering potential benefits for a balanced inflammatory response and antioxidant capacity, citrus flavonoids may address aspects of health that influence the immune system directly, as well as indirectly by helping reduce blood sugar levels.

To fully address the negative impact high blood sugar has on immune health, insulin secretion and glucose uptake must be improved. Lemon flavonoids have demonstrated the ability to inhibit the DDP-4 enzyme, thereby preventing the excessive hydrolysis and eventual breakdown of GLP-1, the hormone responsible for increased insulin secretion.10 When multiple flavonoids work in tandem, the body is able to significantly reduce insulin resistance for improved blood glucose levels.8

As blood glucose levels are normalized, the body’s immune defense has a chance to recover as well. Nature has provided a powerful source of support through citrus flavonoids to supplement efforts toward a healthier lifestyle with some good old lemon-aid.

Editor’s note: This content is intended for informational purposes only; Natural Products Insider does not endorse or encourage claims/marketing to include disease and drug claims.

A third-generation ingredient manufacturer for the natural products industry, Rob Brewster is proud to be part of the health and wellness world. He has followed in his grandfather’s and father’s footsteps, helping their company Brewster Foods grow since he joined in the 1990s, and then partnering with Syntech to form Ingredients by Nature, a global provider of citrus bioflavonoids and extracts. As president, Brewster takes pride in citrus science and continues to invest heavily in citrus flavonoid science for condition-specific applications and holistic wellness.


1 Kim JH et al. “Relationship between natural killer cell activity and glucose control in patients with type 2 diabetes and prediabetes.” J Diabetes Investig. 2019;10(5):1223-1228.

2 Han JL, Lin HL. “Intestinal microbiota and type 2 diabetes: from mechanism insights to therapeutic perspective.” World J Gastroenterol. 2014;20(47):17737-17745.

3 Zhou W et al. “Longitudinal multi-omics of host–microbe dynamics in prediabetes.” Nature. 2019;569:663-671.

4 Berbudi A et al. “Type 2 Diabetes and its Impact on the Immune System.” Curr Diabetes Rev. 2020;16:442.

5 Tsalamandris S et al. “The Role of Inflammation in Diabetes: Current Concepts and Future Perspectives.” Eur Cardiol. 2019;14(1):50-59.

6 Lee JK. “Anti-inflammatory effects of eriodictyol in lipopolysaccharide-stimulated raw 264.7 murine macrophages.” Arch Pharm Res. 2011;34(4):671-679.

7 Gamo K et al. “Hesperetin glucuronides induce adipocyte differentiation via activation and expression of peroxisome proliferator-activated receptor-γ.” Biosci Biotechnol Biochem. 2014;78(6):1052-1059.

8 Ribeiro CB et al. “Effectiveness of Eriomin in managing hyperglycemia and reversal of prediabetes condition: A double‐blind, randomized, controlled study.” Phytother Res. 2019;33:1921-1933.

9 Zaidun NH, Thent ZC, Latiff AA. “Combating oxidative stress disorders with citrus flavonoid: Naringenin.” Life Sci. 2018;208:111-122.

10 Parmar HS et al. “DPP-IV inhibitory potential of naringin: an in silico, in vitro and in vivo study.” Diabetes Res Clin Pract. 2012;97(1):105-111.

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