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Managing immune health is more than just taking a multivitamin and going on all day. Yes, it helps, but the immune system is much more complex than that. Lately, discussions around the immune system tend to focus on maintaining a healthy gut or an appropriate inflammatory response. These are vital parts of a strong immune system, but unfortunately this complex network of cells, tissues, and organs is susceptible to weakening when the body suffers from particular health problems. An underestimated and rarely discussed challenge that can alter the immune system is prediabetes.
According to CDC, about a third of the American population has prediabetes, but more than 84% of these people do not know they have it. Part of the reason could be that although prediabetes makes blood sugar higher than normal, it is not high enough to be diagnosed as type 2 diabetes, and symptoms usually go unnoticed. If left untreated, prediabetes usually turns into type 2 diabetes.
The link between blood sugar and immune health
Consumers know that type 2 diabetes is something to avoid, but they may not realize that one of the main reasons for maintaining adequate blood sugar is that it can help support proper immune defense. Adults with type 2 diabetes have lower natural killer (NK) cell activity than those with lower blood sugar.1 And hyperglycemia affects the immune system in a number of ways, such as by altering the function of white blood cells. At the same time, the increase in sugar can potentially create an imbalanced microbiome with an increase in “bad” bacteria over normal glucose groups.2
But type 2 diabetes is not the time when immune health complications begin. They start when the body begins to develop insulin resistance with the onset of prediabetes. Stanford researchers studying the effects of prediabetes on immune health have found that immune function can be significantly impaired.3 This happens because higher blood sugar levels cause an imbalance of cytokines that provide vital help in signaling immune cells. These researchers were also able to see higher proportions of the Blautia bacteria in the insulin-resistant participants, which led to further deregulation of sugar and a worsening of the prediabetic condition.
Research into the relationship between blood sugar and the immune system has solidified the previously discussed negative effect on cytokine production and immune cell function.4 Cytokines that play key protective roles against pathogens and for the adaptive immune response were suppressed, thereby also suppressing the body’s immune defense. T cells and white blood cell production were reduced, and neutrophils and macrophages weakened, leaving the body open to attack and exacerbating potential health complications.
Fortunately, prediabetes is not the end of the road. Affected people can often change their situation and lower their blood sugar levels, which can also improve immune health. The American Diabetes Association (ADA) recommends taking simple steps to improve diet and exercise to help lower blood sugar. Research has shown that supplementation with citrus flavonoids can help boost these efforts; in fact, the ingredient has shown many potential effects through multiple mechanisms.
Overproduction of pro-inflammatory 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 the increased blood sugar. If left unchecked, the excess will then worsen the condition by worsening insulin resistance. As such, many people with type 2 diabetes are at a higher risk for additional health complications and are more susceptible to infectious diseases.4.5
Citrus flavonoids are able to play a role in providing natural support for a balanced inflammatory response by activating PPARg expression and inhibiting the kappa light chain activating nuclear factor of activated B cells.6 Lemon flavonoids have also been shown that the process of balancing the inflammatory response helps increase adiponectin, which is essential for 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, which makes them popular for use in multivitamins. What’s more, research has shown that citrus flavonoids are able to provide powerful 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 results in an associated reduction in lipid peroxidation, helping to influence a reduction in blood sugar.8 By offering 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 to lower blood sugar.
To fully respond to the negative impact of hyperglycemia on immune health, insulin secretion and glucose absorption must be improved. Lemon flavonoids have been shown to inhibit the DDP-4 enzyme, thereby preventing excessive hydrolysis and eventual breakdown of GLP-1, the hormone responsible for increased insulin secretion.ten When multiple flavonoids work in tandem, the body is able to significantly reduce insulin resistance to improve blood sugar levels.8
As blood sugar levels normalize, the body’s immune defense also has a chance to be restored. Nature has provided a powerful source of support through citrus flavonoids to supplement efforts towards a healthier lifestyle with a good ol ‘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 maker for the natural products industry, Rob Brewster is proud to be part of the world of health and wellness. He followed in his grandfather’s and father’s footsteps, helping their Brewster Foods business grow since arriving in the 1990s, then partnering with Syntech to form Ingredients by nature, a global supplier of bioflavonoids and citrus extracts. As President, Brewster takes pride in citrus science and continues to invest heavily in the science of citrus flavonoids for condition-specific applications and holistic well-being.
The references
1 Kim JH et al. “Relationship Between Natural Killer Cell Activity and Blood Sugar Control in Patients with Type 2 Diabetes and Prediabetes.” J Diabetes Investig. 2019; 10 (5): 1223-1228.
2 Han JL, Lin HL. “Gut microbiota and type 2 diabetes: from understanding the mechanisms to the 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 erodictyol in raw 264.7 murine macrophages stimulated by lipopolysaccharides.” Arch Pharm Res. 2011; 34 (4): 671-679.
7 Gamo K et al. “Hesperetin glucuronides induce adipocyte differentiation via the activation and expression of the γ-receptor activated by peroxisome proliferators.” Biosci Biotechnol Biochem. 2014; 78 (6): 1052-1059.
8 Ribeiro CB et al.. “Efficacy of Eriomin in the management of hyperglycemia and reversal of prediabetes: a double-blind, randomized controlled study.” Phytother Res. 2019; 33: 1921-1933.
9 Zaidun NH, Thent ZC, Latiff AA. “Fighting oxidative stress disorders with the citrus flavonoid: naringenin.” Life Sci. 2018; 208: 111-122.
10 Parmar HS et al. “Naringin DPP-IV inhibitory potential: an in silico, in vitro and in vivo study.” Diabetes Res Clin Pract. 2012; 97 (1): 105-111.
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