The sex hormone estrogen is implicated in hastening the progression of many chronic diseases. In particular, when compared to people with testes, menstruating people with ovaries are at higher risk of developing estrogen-dependent cancers[i], autoimmunity[ii][iii], and more rapid disease progression along with poorer prognosis in respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis[iv][v]. In different tissues estrogen has differing effects that include cell proliferation, immunomodulation, and stimulation of mucin secretion[vi][vii][viii]. Here I will briefly touch on what role estrogen is theorized to play in the pathogenesis of estrogen-dependent cancers and autoimmunity, but I will discuss in more depth the role that it plays in the disease progression of chronic respiratory diseases. Lastly, I will discuss the potential therapeutic effects of phytoestrogens on estrogen-related disease progression.
Estrogen plays a major role in certain hormone-dependent cancers. There are two types of estrogen receptors: estrogen receptor alpha (ER-a) and estrogen receptor beta (ER-b). It is thought that estrogen’s agonism of the ER-a causes cell proliferation indirectly through a paracrine mechanism involving non-proliferating ER-a-positive cells. In addition, the ER-b seems to repress cell proliferation and is pro-apoptotic, therefore the ER-b might generally inhibit the mitogenic activity of estrogens mediated by ER-a[ix][x]. Studies have shown that later-stage breast cancers have an over-expression of ER-a, and an under-expression of ER-b. The breast cancer drug tamoxifen is an ER-a antagonist, but may also act as an ER-b agonist[xi]. Theoretically, by agonizing the ER-b in the earlier stages of estrogen-dependent cancers, tumor growth may be inhibited.
The role of sex hormones in the development of autoimmunity is complex, and sex hormone production and its related risks to autoimmunity may even interface with the human gut microbiome[xii]. Menstruating people are on average 2.6 times more likely than males to develop autoimmunity, and in particular have a significantly higher risk of developing Hashimoto’s, Graves’, Sjogren’s, lupus, multiple sclerosis, and rheumatoid arthritis than males[xiii]. In general, it has been shown that menstruating people/those with ovaries have stronger immune responses than people with testes, and this may lead to an increased production of either auto-antibodies or inflammatory cytokines, both of which make autoimmune symptoms worse. People with ovaries tend to have both stronger cell-mediated immune responses and higher antibody production than males when immunized. The T-cell mediated immune response in females is influenced by sex hormones. A helper T-cell type 1 (Th1) response is a cell-mediated and pro-inflammatory, involving the production of IL-2, IFN-gamma, and lymphotoxin. A Th2 response is less inflammatory but is focused on the production of antibodies. Females are more likely to have a Th1 response when challenged by an infection or antigen, yet during pregnancy the Th2 response is dominant. It is thought that estrogen has a biphasic effect on the immune system, with higher levels stimulating a Th2 response (e.g. during pregnancy and ovulation), and lower levels stimulating a Th1 response (e.g. during menstruation). Progesterone promotes the development of Th2 cells and therefore antagonizes the Th1 response. In females with multiple sclerosis (MS) and rheumatoid arthritis (RA), symptoms can often become worse during menstruation, when estrogen and progesterone are low, and disease can go into temporary remission during pregnancy, when estrogen and progesterone are high. Furthermore, females with MS and RA often experience improvements in their symptoms when using oral contraceptives or hormone replacement therapy. Conversely, females with lupus can see their symptoms worsen with pregnancy or hormone therapy. Testosterone seems to have an anti-inflammatory and immunosuppressive effect on autoimmunity[xiv].
Estrogen affects the respiratory tract in multiple ways. Chronic respiratory diseases such as certain types of asthma, COPD, and cystic fibrosis often involve mucus hypersecretion and bacterial colonization of the lungs. Cystic fibrosis (CF), a genetic disease that results in a thickening of the mucus in the respiratory tract, is typified by chronic Pseudomonas aeruginosa lung infections. Bacterial colonization and mucus hypersecretion in CF, COPD, and non-CF bronchiectasis results in an immune response where neutrophils are over-recruited and inefficient at cleaning up infection, and thus die in large numbers, leaving behind inflammatory cytokines and proteolytic enzymes, such as neutrophil elastase, which cause further airway damage[xv]. Females with CF experience more pulmonary exacerbations during the follicular phase of the menstrual cycle, when estrogen is high[xvi]. Estrogen affects CF pulmonary exacerbations in at least two ways. First, exposure to estrogen causes Pseudomonas aeruginosa (PA) to mutate from its non-mucoid, planktonic form to its mucoid, biofilm-mediated form. PA in its mucoid form is more virulent and more resistant to antibiotics, making it harder to treat. Females with CF are colonized with PA at an earlier age and more often culture mucoid strains than males. Mucoid PA is cultured more often in females during the follicular phase (when estrogen is high) than during menstruation (when estrogen is low)[xvii]. Secondly, the epithelium of the airways changes when exposed to estrogen. When airway tissue is exposed to estrogen, the expression of mucin-producing goblet cells in the epithelium increases by about 635%, while the expression of ciliated cells decreases by about 64%. Furthermore, estrogen increases goblet cell mucin production by about two-fold[xviii].
Phytoestrogens, such as the soy isoflavone genistein, agonize ER-a less strongly than estrogen (estradiol) yet agonize ER-b more strongly than estradiol. In fact, the ER-b has a 30-fold greater binding affinity for genistein than ER-a. By preferentially agonizing the ER-b, which is anti-mitogenic, phytoestrogens may have a role preventing the formation and proliferation of estrogen-dependent cancers, and may even provide a safer alternative to hormone replacement therapy in menopausal women[xix]. While there has been preliminary research on the impacts of phytoestrogens on autoimmunity[xx], more research must be done to determine whether they can be used to reduce disease progression in estrogen-affected autoimmune diseases. The use of phytoestrogens in chronic respiratory diseases like asthma and CF may have beneficial effects in multiple different ways. For example, one study showed that females with CF using oral contraceptives had less frequent pulmonary exacerbations than those not using contraceptives[xxi]. In bronchial epithelium, the ER-b is the predominant type of ER expressed[xxii]. Therefore, phytoestrogens may be a preferential analogue to exogenous estradiol in its effects on the lung. Herbs containing phytoestrogens include red clover, licorice, shatavari, and black cohosh.
However, research on the use of phytoestrogens such as genistein in people with CF has mainly focused on their ability to correct and potentiate mutant CFTR channels in the epithelium, addressing the fundamental cellular defect that leads to CF disease expression. One animal study showed that the expression of CFTR channels in the uterine epithelium is upregulated by genistein supplementation, possibly via agonism of the ER-b, and this results in an increase in luminal fluid accumulation[xxiii]. Several in vitro studies have shown that genistein potentiates gating in wild-type and mutant deltaF508 CFTRs, allowing chloride to flow out of the cell[xxiv][xxv], which in humans would increase water outflow into the mucus lining outside of epithelial cells, ameliorating the fundamental disease process of CF. These studies show that genistein and other isoflavones can have epigenetic effects that may rescue faulty CFTR expression in people with CF. Furthermore, when paired with curcumin, a well-documented corrector of mutant CFTR function, genistein can have a significant potentiating effect on CFTR gating in G551D mutations[xxvi]. Therefore, the epigenetic effects of phytoestrogens may prove very useful in the treatment of CF, and may even be synergistic with pharmaceutical CFTR correctors and potentiators[xxvii].
The use of other herbs that balance menstruation and sex hormone production may also be helpful in minimizing estrogen's negative impact on lung health. Vitex berry (Vitex agnus-castus) is an excellent herb for balancing estrogen and progesterone in people with ovaries, and can alleviate dysmennhorea. Several other herbs may also help female hormone imbalances such as shatavari, black cohosh, licorice, and others. Consult a clinical herbalist to discuss which of these herbs may be most suitable for your constitution and to check for possible herb-drug interactions.
In conclusion, estrogen has a harmful effect on the progression of chronic disease in many people who menstruate. Estrogen can have mitogenic, inflammatory, and mucus hypersecretory effects in certain conditions. Supplementation with phytoestrogens or herbal hormone modulants may have beneficial effects on these mechanisms of disease, and may cause epigenetic changes that result in improved prognosis for people with cystic fibrosis.
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[ii] Jacobson, Denise L., et al. "Epidemiology and estimated population burden of selected autoimmune diseases in the United States." Clinical immunology and immunopathology 84.3 (1997): 223-243.
[iii] Autoimmune Diseases Coordinating Committee. "Progress in Autoimmune Diseases Research: Report to Congress." US Department of Health and Human Services (2005).
[iv] Farha, Samar, et al. "Effects of the menstrual cycle on lung function variables in women with asthma." American journal of respiratory and critical care medicine 180.4 (2009): 304-310.
[v] Johannesson, Marie, D. Ludviksdottir, and Christer Janson. "Lung function changes in relation to menstrual cycle in females with cystic fibrosis." Respiratory medicine 94.11 (2000): 1043-1046.
[vi] Huang, Bo, Margaret Warner, and Jan-Åke Gustafsson. "Estrogen receptors in breast carcinogenesis and endocrine therapy." Molecular and cellular endocrinology (2014).
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[viii] Tam, Anthony, et al. "Estradiol increases mucus synthesis in bronchial epithelial cells." PloS one 9.6 (2014): e100633.
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[xi] Huang, Bo, et al. 2014.
[xii] Markle, Janet GM, et al. "Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity." Science 339.6123 (2013): 1084-1088.
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[xiv] Whitacre, Caroline C., et al. 1999.
[xv] Bergin, David A., et al. "Airway inflammatory markers in individuals with cystic fibrosis and non-cystic fibrosis bronchiectasis." Journal of inflammation research 6 (2013): 1.
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[xviii] Tam, Anthony, et al. 2014.
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[xxi] Chotirmall, Sanjay H., et al. 2012.
[xxii] Tam, Anthony, et al. 2014.
[xxiii] Chinigarzadeh, Asma, et al. "Genistein-induced fluid accumulation in ovariectomised rats' uteri is associated with increased cystic fibrosis transmembrane regulator expression." Clinics 69.2 (2014): 111-119.
[xxiv] Hwang, Tzyh-Chang, et al. "Genistein potentiates wild-type and delta F508-CFTR channel activity." American Journal of Physiology-Cell Physiology 273.3 (1997): C988-C998.
[xxv] Moran, Oscar, and Olga Zegarra-Moran. "A quantitative description of the activation and inhibition of CFTR by potentiators: Genistein." FEBS letters 579.18 (2005): 3979-3983.
[xxvi] Yu, Ying-Chun, et al. "Curcumin and genistein additively potentiate G551D-CFTR." Journal of Cystic Fibrosis 10.4 (2011): 243-252.
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The long term use of stomach acid-lowering drugs such as proton pump inhibitors (PPIs) in the cystic fibrosis (CF) population, both adults and children, has been common for approximately 20 years. Today, more than 50% of CFers are using PPIs[i]. They are used for two main reasons: to treat gastroesophageal reflux and to improve supplemental pancreatic enzyme activation, particularly lipase. However, there are flaws in the reasoning for use of acid-lowering drugs in both of these situations. Firstly, the cause of reflux is not excessive secretion of stomach acid but dysfunction of upper gastrointestinal (GI) motility and secretions[ii], and further reducing gastric acidity with PPIs or antacids will further exacerbate reflux, causing a dependency on the drugs and worsening symptoms over time. Furthermore, the long-term use of PPIs has significant and far-reaching side effects that can negatively affect CF prognoses. Secondly, although several preliminary studies have demonstrated that the pH of the duodenum can be too low to provide the right environmental for supplemental pancreatic enzyme activation, it is not completely clear that bicarbonate secretion is inadequate in all cases, even if steatorrhea is present. A 2014 Cochrane Review of the use of PPIs in CF found that related clinical trials were not only biased, but showed zero or overall insignificant improvement in gastrointestinal symptoms[iii]. In fact, there may be other mechanisms at play within the duodenum that cause steatorrhea and contribute to low duodenal pH, namely inadequate bile secretion, possibly due to a diet low in bitter plant constituents. Here, I will discuss the issue of gastroesophageal reflux disease (GERD) in CF and the negative consequences of using PPIs to treat it. I will also discuss the many negative side effects of long term PPI use in the CF and general populations. In addition, I will discuss the low bicarbonate theory in its relationship to pancreatic enzyme activation, and how the use of PPIs may not be helpful in this situation. Lastly, I will discuss the role of bitter plant constituents in stimulating release of GI hormones and bile in the duodenum, their relationships to macronutrient absorption, and how the use of bitter tastants in the CF population may kill two birds with one stone: addressing GERD by correcting gastric sphincter function and GI secretions, and improving lipase activation by stimulating release of bile which emulsifies fats and stimulates bicarbonate secretion.
Gastroesophageal Reflux Disease
Gastroesophageal reflux disease is a common complaint in the CF population. Possible causes for the prevalence of GERD include frequent antibiotic use (for treatment of respiratory infections) that disrupts the gastrointestinal microbiome[iv], and the Standard American Diet and CF diet recommendations. These diets are high in low-quality fats (i.e. industrial seed oils) and refined carbohydrates, guaranteeing a shift in the gut microbiome[v] that can also contribute to GERD. Another likely contributing factor of GERD in CF is a low-plant diet. In terms of GERD treatment, the use of PPIs and other acid-lowering drugs actually makes GERD worse over time and significantly increases the likelihood of patients becoming increasingly dependent on PPIs to address symptoms of reflux. Reflux coincides with low stomach acid in the majority of cases[vi] [vii] [viii], because the lower esophageal sphincter (LES) closes upon release of gastrin[ix] and exposure to stomach acid, preventing acid from moving upward into the esophagus. Episodes of reflux are most commonly the result of transient lower esophageal sphincter relaxations (TLESRs) that happen during stomach distention and subsequent gas release after meals, and are exacerbated with consumption of fermentable carbohydrates[x] [xi]. This could mean that excessive bacterial carbohydrate fermentation due to intestinal dysbiosis is a likely comorbidity in reflux diseases, and therefore the most sustainable treatment method would be to correct the underlying dysbiosis with dietary, herbal, and lifestyle changes.
Most health care practitioners still believe that reflux is caused by excessive stomach acid production, thus many practitioners rely almost exclusively on acid-lowering drugs to treat GERD. PPIs work by blocking the gastric acid pump in the parietal cells of the stomach from secreting protons[xii]. By blocking acid secretion they can produce a short-term reduction of acid reflux into the esophagus by reducing total gastric acid load. However, studies have also shown that low stomach acid (hypochlorhydria) contributes to delayed gastric emptying (gastroparesis)[xiii] [xiv], which is a major contributing factor of stomach distention and subsequent weakening of the LES, leading to TLESRs[xv]. Gastroparesis is a fairly common complaint in cystic fibrosis, especially in children, and is likely due to hypochlorhydria. Therefore, taking acid-lowering drugs reduces LES tone, allowing stomach acid to continually reflux up into the esophagus with no way to suppress tissue damage by the acid except with more acid-lowering drugs, creating a vicious cycle and drug dependency.
In addition to over-relaxation of the LES, long term PPI use can result in protein malabsorption and protein-bound nutrient deficiencies, since gastric acid is an essential part of protein digestion. This is especially concerning for CFers who commonly already have protein and fat malabsorption issues. Gastric acid digestion of protein is an important first step in protein digestion before proteases (contained in pancreatic enzymes) can work effectively. Furthermore, a number of insidious nutrient deficiencies can result from hypochlorhydria including vitamin B12 deficiency, iron deficiency and anemia, calcium deficiency and osteopenia, and magnesium deficiency[xvi] [xvii].
Moreover, having low stomach acid significantly increases the risk of gastric and enteric infections from pathogens such as Clostridium difficile[xviii], which have become more common in the CF population, especially during hospitalizations[xix]. Stomach acid is a primary barrier against infection of the human digestive system, and low stomach acid can lead to dysbiosis[xx]. A multi-center study showed that in children, acid-suppressing drugs increased the risk of both GI infections and community-acquired pneumonia, likely due to disruption of the microbiome and interference with normal white blood cell activity[xxi]. Acid-lowering drugs dampen the immune response by effecting leukocyte activity, especially the bactericidal activity of neutrophils[xxii].
Lastly, use of PPIs in the CF population increases the frequency of pulmonary exacerbations[xxiii] likely due to increased risk of aspiration of stomach acid and bile acids, as well as functional changes in white blood cell activity. In GERD, not only is LES tone reduced, but often pyloric sphincter tone is also reduced, allowing bile acids to move from the duodenum into the stomach and reflux into the esophagus. One study found that bile acids were present in 86% of the aspirate of people with GERD, compared to 58% in normal subjects, with aspiration worst after meals and laying down[xxiv]. Another study found that people with advanced lung disease are more likely to aspirate bile acids, which contribute to further lung injury[xxv]. Bile acid reflux and aspiration is higher in CF than in healthy controls, with post-transplant patients at even higher risk. Bile acid reflux also corresponded to unexplained cough episodes in the CF study group. PPI use doe not help patients with bile acid reflux[xxvi], and may even exacerbate it. Mucosal damage is much greater when bile acids are present in refluxate compared to acid reflux alone, and a major cause of alkaline (bile acid) reflux is gallbladder removal[xxvii] and/or inadequate choleresis. Cholecystokinin (CCK) is a hormone released when the GI tract detects fats or bitter substances, and is responsible both for the closure of the pyloric sphincter and release of bile from the gallbladder[xxviii]. Without adequate secretion of CCK (due to a diet deficient in bitter plants and/or fats) the pyloric sphincter may not close properly and bile acid reflux may result. A slow leakage of bile from an unstimulated gallbladder, or from the liver when the gallbladder has been removed, can contribute to bile acid reflux when pyloric sphincter tone is weak. Furthermore, proteolytic enzymes are activated when pH is above 2 for pepsin, and 5 for trypsin, and so if these activated enzymes are refluxed into the esophagus and possibly aspirated, this can cause even greater mucosal damage[xxix]. This is another important reason why gastric pH must be kept acidic: to prevent activated enzyme reflux.
Duodenal Acidity and Pancreatic Enzyme Activation
The second reason that PPIs are used in CF is that some studies have shown duodenal pH to be excessively acidic[xxx] [xxxi]. It has been theorized that deficient pancreatic bicarbonate secretion is responsible for this. In vitro and animal studies have shown that mutations in the CFTR do impair bicarbonate secretion[xxxii]. Although several studies have measured duodenal pH in the CF gut, I could find none that measured bicarbonate secretion directly. Therefore, the mainstream assumption that bicarbonate secretion is inadequate in the CF gut is largely unsupported by scientific evidence. By raising gastric pH, PPIs subsequently raise the pH of chyme leaving the stomach, providing a more alkaline environment for supplemental enzymes’ enteric coating to break down (which dissolves above a pH of 5.8) and preventing the enzymes from being denatured at a pH of 4.0 or below[xxxiii]. While taking PPIs may indeed help bring the pH of chyme to a level appropriate for enzyme activation, the effect that they have on reducing overall stomach acid levels will produce all of the side effects previously mentioned when used long term. Using these drugs for the purpose of enhancing fat absorption will conversely reduce absorption of protein and protein-bound nutrients. Furthermore, studies have shown duodenal pH in CFers varies greatly, and in some it is normal[xxxiv]. Clinical experience has shown that introduction of PPIs does not guarantee improved fat absorption but instead may create serious side effects with long-lasting or permanent consequences[xxxv].
In CF, an alternative reason why fat malabsorption may be present (even concurrent with PPI therapy) is deficient bile production and/or bile flow, given that some CF patients may develop liver and/or gallbladder pathologies, or functional inadequacies. Bile is a critical part of fat digestion as it emulsifies fats, breaking them into micelles so that lipase can further break them down into fatty acids for absorption into the portal vein. Without adequate bile, supplemental lipase may not work effectively. I propose that a major cause of fat malabsorption in CF is inadequate bile secretion due to a common absence of bitter constituents in the CF diet. Bile itself has a moderately alkaline pH of between 6 and 8.5 [xxxvi], therefore it may contribute somewhat to the neutralization of acid in chyme entering the duodenum. Furthermore, the presence of bile stimulates the release of pancreatic bicarbonate into the lumen[xxxvii], therefore bile secretion may also have an indirect role in neutralizing the acid in chyme. In addition, the presence of acidic chyme entering the duodenum stimulates the secretion of secretin, a hormone that stimulates bicarbonate release from the pancreas, bile production in the liver, and inhibits gastrin and stomach acid secretion[xxxviii]. If the chyme entering the duodenum is not acidic enough (due to hypochlorhydria and/or PPI use) to trigger the release of secretin, this may further impede mechanisms to alkalize the duodenum. It is therefore possible that fat malabsorption in CFers taking pancreatic enzyme supplements is due not from a pathological inability to produce enough bicarbonate, but from a functional (and therefore reversible) bile deficiency, or even hypochlorhydria. I will next discuss how bitter plant constituents may help with these issues.
Bitter Plant Constituents’ Roles in Aiding Digestion in CF and Beyond
Mainstream nutritional recommendations given to CF patients emphasize calories from fat, protein, and refined carbohydrates at the expense of foods that are high in phytonutrients but low in calories (i.e. vegetables and fruits). One important class of plant constituents contained in many vegetables, especially leafy greens, is bitter tastants. Bitter compounds in plants, especially wild plants or gently bred food crops like kale or arugula, include lactones, iridoids, and alkaloids[xxxix]. Bitter compounds agonize the TAS2R bitter taste receptors located on the tongue, all along the GI tract, on immune cells, on respiratory cells, and even in the brain[xl] [xli]. The human digestive system coevolved with these bitter constituents in plants and the lack of them in the modern diet can cause significant functional deficiencies that lead to gastrointestinal distress and malabsorption, especially in populations who already have primary GI pathologies, such as cystic fibrosis.
Bitter taste receptor stimulation has cascading effects mediated by the vagal nerve. In the GI tract, agonism of bitter receptors stimulates the release of CCK, which stimulates gastric secretions, bile release, insulin production, pancreatic enzyme secretion, and eventually leads to bicarbonate release from the pancreas[xlii]. Bitter stimulation and release of CCK will also constrict the pyloric sphincter, preventing alkaline reflux[xliii]. Human coevolution with plants created these responses to prepare the digestive tract for potentially harmful plants ingested, as maximization of digestive secretions ensures reduced ingestion and optimal metabolism of toxic chemicals, many of which taste bitter. With a deficiency of bitter tastants in the diet, the GI tract lacks the cues it needs to stimulate adequate release of GI secretions, leading to low stomach acid, poor fat metabolism, deficient pancreatic enzyme release in the non-CF population, sluggish hepatic metabolism, inadequate bicarbonate release, and acid/alkaline reflux. That is, in general, a lack of bitters can lead to indigestion. Increased GI secretions with bitter taste receptor stimulation means more efficient digestion of food and increased nutrient absorption, two things that the CF population is generally very concerned about.
In several studies on healthy humans and animals, agonism of the bitter taste receptors reduces appetite, induces feeling of satiation earlier in the meal, and slows gastric emptying[xliv]. However, in populations with already decreased appetite and delayed gastric emptying, as in many people with CF, bitter taste stimulation seems to have the opposite effect, increasing appetite and possibly even hastening gastric emptying[xlv]. The amphotericity of bitter tastants may be due to the fact that in many people with CF gastrointestinal secretions are reduced at baseline, leaving one ill-prepared for a meal. But when stimulated with a bitter tastants, secretions may increase to physiologic levels, which may have a positive effect on appetite and gastric emptying.
To stimulate GI secretions and to prepare the digestive tract for an impending meal, bitter tastants from plants can be taken by mouth 5-15 minutes before a meal. This can be in the form of a salad of bitter greens like arugula or dandelion greens, or a medicinal preparation (often alcohol extract) of bitter herbs like gentian root, dandelion root, motherwort, artichoke leaf, yellowdock root, and many others. It is traditional in many cultures for a pre-meal appetizer to feature bitter or pickled foods or herbs before the main course as a digestive aid. If the individual currently suffers from painful GERD symptoms and/or is using PPIs, introduction of bitters may need to slow as the GI tissue is encouraged to heal with soothing anti-inflammatory herbs, and as the individual is slowly weaned off of PPIs.
It is clear that there is indeed great promise for the use of bitter tastants in the management of GERD, enhancement of fat absorption, and improvement of appetite and gastric emptying in CF patients. This is especially true since pharmaceutical options for treatment of these issues, such as PPIs, are inadequate at best and iatrogenic at worst. Further study is needed on the use of digestive bitters as GI secretory stimulants, as well as their ability to improve clinical outcomes in gastrointestinal pathologies of CF patients.
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[xxxix] Valussi, Marco. "Functional foods with digestion-enhancing properties." International journal of food sciences and nutrition 63.sup1 (2012): 82-89.
[xl] Lee, Robert J., and Noam A. Cohen. "Bitter taste bodyguards." Scientific American 314.2 (2016): 38-43.
[xli] Behrens, Maik, and Wolfgang Meyerhof. "Gustatory and extragustatory functions of mammalian taste receptors." Physiology & Behavior 105.1 (2011): 4-13.
[xlii] Valussi, Marco. 2012.
[xliii] Fisher, et al. 1973.
[xliv] Sternini, Catia. "Taste receptors in the gastrointestinal tract. IV. Functional implications of bitter taste receptors in gastrointestinal chemosensing." American Journal of Physiology-Gastrointestinal and Liver Physiology 292.2 (2007): G457-G461.
[xlv] Personal experience and conversations with other CF patients. Facebook. 2013-2015.
Hello friends. I'm excited to announce that I am now publishing online classes on herbal medicine, nutrition, supplementation, and more! It seems that sharing my knowledge and experience through online videos may make it more accessible to different learning styles. If you'd like to learn more, please visit the Classes page here.
In addition, I now have a Patreon membership program! Patreon is an online platform where subscribers can contribute a small monthly amount (as low as $1) to support the content I've provided for free on my website since 2013. Members get a host of benefit options including early-bird discounts on classes, an invitation to a private Facebook group, an invitation to a monthly live Q&A with me, monthly one-on-one herbal consultations, and more. Click here to learn more about Patreon!
Back in 2014, I conducted a series of experiments inhaling essential oils through my nebulizer. I began these experiments at a time when I was due to use oral antibiotics again (a regular occurrence for me as a result of my chronic cystic fibrosis lung infections) but a snow storm prevented me from getting to the pharmacy. As they say, necessity if the mother of invention (or in this case, discovery)!
Why Use Essential Oils?
In 2014, I was in the midst of my clinical herbal training and had been learning about various medicinal plant constituents. In particular, the constituents called essential oils often have potent antimicrobial (antibacterial, antifungal, & antiviral) power. So I decided it was time to try an experiment with them to see if they could help me control my lung infections. I was very happy with the results and I'd love to share my findings with you!
For the last ten years or so I've struggled with reactive hypoglycemia related to CFRD (cystic fibrosis-related diabetes). In the last couple of years it has become very difficult to manage. Reactive hypoglycemia is a condition where the blood sugar crashes 1-3 hours after a meal containing carbohydrates, leading to distressing hypoglycemia symptoms such as shakiness, anxiety, weakness, brain fog, fatigue, tachycardia, and in severe cases, unconsciousness or even coma. Reactive hypoglycemia is more common in CFRD than many CF-specialists realize. Despite avoiding simple carbohydrates and adhering to a Paleo-ish diet for many years, my reactive hypoglycemia has only gotten worse. That is, until I started a ketogenic diet in October of 2020. I've made a remarkable improvement in my blood sugar control and I'd like to report my success in detail here.
Bloating, gas, stomachs aches, indigestion, constipation, diarrhea, reflux... there is a special kind of miserable when we experience these symptoms! In cystic fibrosis and other digestive diseases, these symptoms may be a common nuisance. Fortunately, herbal medicine has several thousand years of clinical experience assisting people with these issues! Using specific medicinal herbs is one of the most effective ways to improve human digestion, which all of our ancestors have been doing for eons. Interestingly, digestion is one of the things that I feel conventional medicine has the hardest time understanding and helping with, especially with regards to chronic digestive issues. In this article I briefly mention a few herbs and techniques to use to address bloating and indigestion. There are so many herbs that help with digestive issues of all sorts that I couldn't possibly discuss them all in one article, but I'll touch on a few that I use most frequently for myself and my clients.
Inflammation is a huge factor in the disease processes of cystic fibrosis. Some studies have shown that faulty CFTR mutations may directly result in inadequate quenching of radical oxygen species (ROS) or excessive release of other inflammatory compounds like cytokines [1,2]. In addition, our burden of chronic infection and gastrointestinal complications contribute secondary sources of inflammation. Chronic inflammation can lead to both localized and systemic issues. Localized inflammation in the lungs can lead to deficient and/or over-reactive immune responses, bronchitis, scarification and airway remodeling, allergies/asthma/hyper-reactive airway diseases, hemoptysis, pleurisy (inflammation of the pleura), and worsened infection. Localized inflammation in the gut can lead to reflux/GERD, esophagitis, gastritis, pancreatitis, gallbladder issues, liver issues, food sensitivities, malabsorption, autoimmune issues of the intestines, gut infections, general indigestion, and excessive mucus production in both the guts and the lungs (by vagal reflex). Systemic inflammation can cause insulin resistance, body pain, arthritis, achey joints and muscles, fever, fatigue, increased risk for autoimmunity, and increased risk for cardiovascular disease.
In this article, originally published in AromaCulture Magazine in July, I discuss herbal and dietary support for CF children and adults. I discuss digestion, respiratory disease, liver support, and modulation of CFTR sodium chloride channels by natural means.
Cystic fibrosis is an autosomal recessive genetic disease that leads to the malfunctioning of several organ systems but most especially impacts the lungs, sinuses, and digestion. It is the most common autosomal recessive genetic disorder (meaning that each parent must be a carrier of the genetic mutation) in people of Western European decent. There are approximately 30,000 people living with cystic fibrosis (CF) in the United States, and more than 70,000 people worldwide.
For many years I've struggled with the choice of when to avoid antibiotics and what situations warrant their use. As a person with chronic lung infections related to cystic fibrosis, antibiotics have saved my life countless times, but in the last few years I've become dependent on them to function normally. Without antibiotics to control my chronic lung infections (MRSA and Pseudomonas), I often feel debilitating fatigue, get a daily fever, and cough lots and lots of mucus. While I've foind many natural remedies over the years to reduce my infections, improve my immune system, and strengthen my overall health and digestion, the severity of my infections is such that I cannot avoid antibiotics completely.
As a result of my experiences both with conventional pharmaceuticals and natural medicine, my opinions about antibiotics have changed over the years. In the beginning of my healing journey and experimentation with natural medicines, I viewed antibiotics with skepticism and tried to avoid them as often as possible. I made the personal choice to suffer through many months of infection, fatigue, and heavy mucus loads in order to minimize my exposure to this class of drugs. I did this for two major reasons: minimizing the risk of developing antibiotic resistance, and mitigating the impact that excessive use of antibiotics has on the gut microbiome. For about four years, I chose to wait as long as possible between hospitalizations, and do without oral antibiotics for longer and longer periods of time.
Upon reflection, I think avoiding antibiotics as often as I did was a mistake, and I wouldn't recommend people do what I did. I lost lung function during that period and developed some serious and irreversible lung damage. It's not clear whether or not this damage would have developed anyway, even if I had taken more antibiotics. I now believe that the cost-benefit analysis weighs out in favor of using antibiotics when appropriate. In the last year or so I have changed tactics and my health has benefited. Here, I will describe my experiences and review why I made these changes.
A friend of mine with CF who lives in South Africa has a history of severe gastroparesis (delayed gastric emptying) and low stomach acid, which (alongside her Crohn's, CFRD, and removal of her terminal ileum, ascending colon, and gallbladder years ago) has caused her significant digestive distress and inability to digest anything other than her extremely regimented liquid diet. For years Paula's gastroparesis has been so bad that if she doesn't eat precisely the right thing in precise quantities at precisely the right time of day, her stomach will not empty, which puts pressure on her diaphragm and lungs and can cause significant respiratory distress and vomiting. She is a great researcher and has tried many, many things to help this situation, but nothing had yet made a significant dent on these distressing symptoms (including multiple motility drugs). I've tried to strategize with Paula to figure out what was causing or had caused the issue, and secondly what do we do about it now. After a lot of trial and error, it seems we've found two things that have made a big difference in her life: lecithin and artichoke leaf (Cynara scolymus).
Mica McDonald (they/he) is a clinical herbalist, nutritionist, ecologist, and writer living in Abenaki territory (Vermont).