For patients with allergic rhinitis and other allergic conditions, finding long-lasting, effective and well-tolerated treatment of symptoms can be a major challenge. Antihistamines may help to resolve common symptoms like sneezing, swelling, hives, and eye-watering, but relief often comes at a cost: after taking antihistamines, many patients experience dry mouth, dizziness, sleepiness, and other side effects that can be just as disruptive to daily life as allergy symptoms themselves. There are also certain allergy symptoms, such as photosensitivity and contact dermatitis, that do not respond well to treatment with antihistamines.
Because antihistamines do not offer the ideal solution for all patients, researchers have recently been looking into various alternatives to create more complete symptom relief without compromising quality of life. One promising option is quercetin, a flavonoid compound found in many vegetables, fruits, and flowers. Early research in vitro and in animal models has provided insight into the potential benefits of using quercetin as an alternative to antihistamines. Comparative studies also suggest that quercetin may be more effective than some of the other therapeutic alternatives to antihistamines that have been developed.
Using Quercetin to Reduce Allergic Symptoms
For years, scientists have recognized the wide range of potential health benefits of quercetin, which stem from the compound’s antioxidant, antimicrobial, anti-inflammatory, and even anti-carcinogenic activity in cells. However, comprehensive clinical trials are lacking, so the specific clinical implications of quercetin’s unique properties are not fully clear. Still, in vitro and in vivo animal studies have provided intriguing initial insights. One such study was published in BMC Complementary & Alternative Medicine in 2016. Using rat models of allergic rhinitis, a group of researchers from Showa University in Japan was able to demonstrate that quercetin has the potential to reduce nasal allergy symptoms and promote molecular changes in nasal fluids that are associated with a dampening of the inflammatory response to common allergy triggers.
The evidence the researchers presented was based on a week-long intervention, in which the responses of rat models to varying dosages of quercetin were carefully monitored and recorded. First, nasal allergy symptoms were induced in the rats through a well-established sensitization procedure. When the rats were introduced to nasal allergy-inducing challenges, the researchers counted their sneezing and nasal-rubbing behaviors during the first ten minutes after encountering a trigger. In addition, six hours after each challenge, the levels of three allergy-related neuropeptides (substance P, nerve growth factor, and calcitonin gene-related peptide) were measured. Not only did the researchers find that oral administration of quercetin could reduce sneezing and nasal rubbing movements in the rats, but they also reported statistically significant increases in all three neuropeptides. By combining molecular evidence with direct observations of symptom reduction in animal models, this study provides strong evidence that quercetin may be an effective alternative for antihistamines.
Of course, animal model studies do not always translate directly to humans, so patients and practitioners who are considering quercetin as an alternative to antihistamines may need to explore different dosage and administration options. In the study on rats, the researchers found that the minimum dosage for significant inhibition of symptoms was 25 mg per kg of body weight per day. It is not clear whether a similar dosage would be needed for human patients, especially since some of the latest quercetin supplements are strategically designed to increase bioavailability, which may make lower doses more effective. When acting on the results of this study, practitioners and patients may also take note of the fact that the researchers only observed significant decreases in symptoms and increases in neuropeptides after at least five days of quercetin supplementation. This suggests that a long-term, ongoing supplementation approach may make sense for patients who are considering quercetin as an alternative to antihistamines.
Comparing Alternatives to Antihistamines: Quercetin vs. Cromolyn
Like quercetin, disodium cromoglycate—more commonly known as cromolyn—has been presented as a possible alternative to antihistamines for patients with allergic rhinitis and other allergic conditions. This compound is considered a “mast cell stabilizer” because it works primarily by inhibiting the release of cytokines from mast cells. A mast cell is a certain type of immune cell in the blood, and these cells release cytokines, which are proteins that communicate with other cells about initiating an escalating an immune response. Therefore, mast cell stabilization can help stop inflammatory processes from starting and/or progressing. So far, the results from preliminary, small-scale clinical studies on cromolyn are promising: the compound has few known side effects, and in controlled studies where the symptom-reduction effectiveness of quercetin was compared to that of antihistamines, steroids, and placebo, cromolyn proved to offer the most significant benefits.
However, for patients and practitioners who are exploring the various alternatives to antihistamines, it can be helpful to look at studies that directly compare the options. In 2012, a research group from Tufts University conducted a series of in vitro experiments to explore differences in the effectiveness of quercetin and cromolyn for mast cell stabilization. Using cultured human mast cells, they found that quercetin was more effective than cromolyn for inhibiting the release of IL-8 and TNF—two cytokines that are both released by mast cells as part of the immune response. In addition, treatment with quercetin had implications for other anti-inflammatory processes, such as the inhibition of NF-kappa-B (a protein involved in immune-related cell-to-cell communication) and a decrease in calcium levels in the cytosol (which indicates that immune cells are not activated). Neither of these effects was evident in the experiments on cromolyn. Other researchers have also cited anti-allergic immune response activities of quercetin, including the suppression of other compounds produced by mast cells and the prevention of unnecessary antibody formation.
Not only does this research study suggest that quercetin is a more effective mast cell stabilizer than cromolyn, it also indicates that a quercetin supplement is a better preventive therapy for patients with ongoing symptoms. In their experiments, the scientists from Tufts found that cromolyn only stabilized mast cells after they had been stimulated by a trigger and induced symptoms, while quercetin works prophylactically—that is, it displays antioxidant and immunosuppressive activities in the absence of a trigger, so proactive patients may use it to prevent future symptoms from arising. It should be noted that this finding is consistent with the results from the Japanese research group since they too reported that the effects on rats were greatest after they had been taking quercetin supplements for at least five days. Based on these results, quercetin presents a promising alternative for patients and practitioners who are interested in a safe preventive supplement for long-term symptom relief.
Looking Ahead to Larger Clinical Trials
So far, results from clinical trials on alternatives to antihistamines like quercetin and cromolyn are fairly limited. For instance, as part of their study, the research group at Tufts University included two pilot, open-label clinical trials on quercetin, and their findings suggested that quercetin may significantly decrease contact dermatitis and skin photosensitivity, especially when provided in bioavailable forms. However, their tests were conducted on a group of only ten patients, and they only addressed two symptoms. In the future, larger-scale studies may provide greater insight into the specific benefits of individual antihistamine alternatives. Until then, patients and practitioners can draw from the preliminary findings to explore whether a supplement like quercetin may offer symptom relief for individual patients who are seeking alternatives to antihistamines.
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