Editor's note: Although this article deals with asthma and chronic obstructive pulmonary disease (COPD), it may be additionally relevant to COVID-19.
Chronic respiratory disease is one of the underlying health problems associated with severe cases of COVID-19, and interesting anecdotal reports - Dr. Stadtherr's is one - suggest there is a role for carbohydrate restriction in treating other lung diseases.
Observations of those who recover from COVID-19 indicate that survivors may be left with reduced lung function. We don't yet know whether the information that applies to asthma and COPD will apply to the breathing difficulties experienced after COVID-19.
The two most common chronic lung diseases are asthma and COPD. It's estimated that at least 384 million people across the globe have COPD and 334 million people have asthma. COPD is now the third leading cause of death worldwide.
While smoking is the main cause of COPD in the United States, studies estimate that 24% of those with COPD have never smoked. In these cases, the causes for COPD may include occupational exposure and genetic conditions.
Individuals with asthma and COPD are at risk for acute exacerbations, or flare-ups, of their chronic lung disease, often severe enough to require hospitalization. COPD exacerbations, which are most commonly triggered by infection and exposure to irritants, rank among the top reasons for hospitalization.
1. Diet and lung function
Modern medicine offers us a variety of interventions that target specific disease mechanisms: one drug, one target. In the case of lung diseases such as asthma and chronic obstructive pulmonary disease (COPD), for example, the primary (perhaps sole) target of drugs is inflammation.
Although inflammation is indeed a key player in acute episodes of COPD and asthma, there are other relevant mechanisms current treatments do not target and perhaps many more that we have yet to discover.
Other than advising patients to stop smoking, doctors only treat the symptoms of COPD. Medications such as bronchodilators and steroids are the mainstays of treatment, both in maintenance phase and during exacerbations.
Similarly, asthma is treated mainly with bronchodilators and steroids, and patients are told to control their exposure to allergens or irritants that may worsen asthma symptoms.
The role of nutrition in managing lung disease has largely been ignored. Yet there are numerous anecdotal reports that a low-carb diet can help reduce the symptoms and severity of lung disease and perhaps fully eliminate them in some individuals.
Current nutrition guidelines for COPD focus primarily on correcting malnutrition and providing adequate energy intake to prevent weight loss.
Even in the absence of respiratory disease, malnutrition causes decreased respiratory muscle mass and function, a problem with more significant implications in those with chronic lung disease.
According to the Academy of Nutrition and Dietetics, macronutrient advice should be based on a patient's preference, because there is limited evidence for recommending any specific macronutrient composition.
For this reason, there is no current guidance for changing diet composition in people with COPD.
Despite a lack of formal recommendations, however, some lung disease specialists (pulmonologists) have recognized the utility of low-carb, ketogenic diets in COPD. Dr. Albert Rizzo, MD, the chief medical officer of the American Lung Association, acknowledges the potential benefit of the ketogenic diet in COPD, citing anecdotal evidence: "Some notice they can walk faster and climb steps easier."
Dr. Raymond Casciari, MD, another pulmonologist, states: "If you eat a high-carbohydrate diet and you have COPD, you will wind up more short of breath ... The best kind of diet for a person with COPD is a high-fat, high-protein, low-carb eating plan like the keto diet."
There are several mechanisms by which diet could play a role in lung disease. Carbohydrate restriction may benefit both acute exacerbations and chronic problems of lung disease by the following mechanisms:
- Reducing inflammation
- Reducing high blood sugars
- Reducing carbon dioxide production
- Improving nutrition density of meals
2. Lung disease, diet, and inflammation
Doctors understand that both asthma and COPD are defined by inflammation of the airways. Asthma is characterized by periodic, reversible airway inflammation, while COPD is defined by persistent airflow obstruction, mainly from emphysema and chronic bronchitis.
Exacerbations of asthma and COPD are also characterized by inflammation. This inflammation results in increased coughing (sometimes productive or "wet," producing mucus or phlegm), shortness of breath, and wheezing.
Depending on the severity of the exacerbation, patients may require breathing treatments that help open the airways (bronchodilators), antibiotics, steroids, supplemental oxygen, and even hospitalization.
Carbohydrate restriction reduces inflammation
Given that COPD and asthma are driven by inflammation, any intervention that reduces inflammation could theoretically have a beneficial effect on these chronic lung diseases.
Low-carb diets can result in reduced markers of inflammation for many individuals and thus may be useful in lung disease. A very low-carb, ketogenic diet, specifically, is known to suppress an important mediator of inflammation involved in COPD called the NLRP3 inflammasome.
Nutritional ketosis suppresses the NLRP3 Inflammasome
The NLRP3 inflammasome is a cellular inflammatory complex implicated in COPD exacerbations and has been shown to be triggered by infections, cigarette smoke, and air pollutants. It is thought to be involved with the development and progression of COPD and to play a significant role in acute exacerbations.
The ketone body beta-hydroxybutyrate suppresses the activation of the NLRP3 inflammasome. For this reason, a well-designed ketogenic diet theoretically may reduce inflammation associated with COPD exacerbations. The clinical significance of this suppression of inflammation is unknown at this time, but is a promising feature in the role of the ketogenic diet as a treatment for COPD.
3. High blood sugar and lung disease
High blood sugar is common during lung disease exacerbations, both as a response to stress and as a side effect of medical management.
Because they reduce inflammation, steroids (glucocorticoids) are a standard part of treatment when a patient has a COPD exacerbation. It is estimated, however, that 45% of individuals treated with steroids for COPD exacerbations develop steroid-induced diabetes.
Hyperglycemia occurs in the majority of hospitalized patients receiving high-dose corticosteroids (prednisone greater than or equal to 40 mg daily), a standard intervention for acute exacerbations. This hyperglycemia likely occurs because steroids induce insulin resistance, increase liver gluconeogenesis, and impair pancreatic beta-cell function. Furthermore, other standard medical interventions, including inhaled bronchodilators and certain antibiotics, may also cause hyperglycemia.
Hyperglycemia is associated with adverse outcomes
Just as diabetes is associated with worsened outcomes in many other medical conditions, hyperglycemia is associated with poor outcomes in patients admitted to the hospital with acute exacerbations of COPD.
Blood sugar levels greater than 126 mg/dL (7.0 mmol/L) within 24 hours of admission are associated with worse outcome in patients with COPD exacerbations requiring noninvasive breathing assistance (commonly known as CPAP or BiPAP).
In patients with pre-existing diabetes, the risk may be even higher, as they are often already starting with a higher glucose level and therefore may be more sensitive to steroid-induced hyperglycemia.
Pre-existing hyperglycemia also makes these patients more prone to exacerbations of their lung disease.
Not only is hyperglycemia relevant in the setting of exacerbations, but long-standing hyperglycemia also has a significant impact on the long-term course of lung disease:
- Type 2 diabetes is associated with worsening progression of COPD and increased COPD-related mortality.
- Results of pulmonary function tests are decreased in those with type 2 diabetes compared to healthy controls.
- For individuals with COPD, higher fasting glucose (as seen in metabolic syndrome) is associated with increased frequency of exacerbations.
- People with diabetes are more likely to have reduced pulmonary function, reduced exercise capacity, and reduced quality of life compared to people without diabetes.
- When patients with diabetes and COPD are hospitalized for an exacerbation, 50 - 80% of them experience high blood sugars. This means they are also more likely to have longer hospital stays and increased mortality compared to patients without diabetes.
Hyperglycemia disrupts airway glucose homeostasis
High glucose levels in the blood are associated with high levels of glucose in the airways. There are several mechanisms directed at regulating the amount of glucose in our airways, but these mechanisms are disrupted by hyperglycemia and airway inflammation.
Glucose in the airways also likely serves as a nutrient source for bacteria and stimulates proliferation of many respiratory bacteria, possibly contributing to infections and exacerbations of chronic lung disease.
- COPD patients with diabetes or hyperglycemia are more likely to have bacteria grow from their sputum cultures.
- In cystic fibrosis, diabetes and hyperglycemia are associated with worsening of disease and respiratory infections.
Metformin, a medication that reduces insulin resistance and subsequently reduces hyperglycemia, is associated with reduced bacterial growth in airways.
In one observational study, patients with asthma and diabetes who took metformin had a five-fold lower risk of asthma-related hospitalization and two-to three-fold lower risk of asthma exacerbations.
Carbohydrate restriction reduces hyperglycemia
Carbohydrate intake is the main dietary determinant of blood glucose. Therefore, carbohydrate restriction is a logical intervention in the prevention of steroid-induced hyperglycemia. Since improving overall glycemic control is associated with improved outcomes in both chronic and acute lung disease, a low-carb diet has the potential to dramatically alter the clinical course of lung disease.
4. Diet and carbon dioxide production
In simple terms, the lungs are responsible for bringing oxygen into the body and removing carbon dioxide from the body.
Macronutrient intake affects carbon dioxide production
The amount of carbon dioxide produced from food differs depending on whether the food is made up predominately of carbohydrate, protein, or fat. We measure this by comparing how much carbon dioxide is produced relative to oxygen consumed when food is being metabolized.
This ratio is called the respiratory quotient or RQ.
Carbohydrate produces the most carbon dioxide and has the largest RQ of 1.0. The RQ for fat, however, is only 0.7, indicating that less carbon dioxide is produced from eating fat. Protein falls somewhere between those two, with an RQ of 0.8.
Why is this RQ value important? Because the body must get rid of the carbon dioxide it produces. As more carbon dioxide is created by the burning of fuel inside our bodies, our lungs need to work harder to blow off the carbon dioxide that accumulates.
Consider an analogy to help understand the significance of RQ:
Carbon dioxide is like smoke in a house, produced by burning fuel inside the house. When carbohydrates are burned (high RQ), there is a lot of smoke production, and it will take more ventilation inside the house to remove the smoke from the air. In contrast, burning fat (a lower RQ) produces less smoke and therefore does not require as much ventilation to clear the air.
Healthy individuals (with healthy lungs) can easily compensate for higher carbon dioxide production by increasing air exchange, or ventilation. Those with lung disease, however, may not be able to increase ventilation and may therefore develop high levels of carbon dioxide in the blood (a potentially dangerous condition called hypercapnia).
Thus, it may be favorable to reduce carbohydrate intake and increase fat intake to reduce production of carbon dioxide. The less carbon dioxide that is produced, the less effort it takes to get rid of it.
Carbohydrate restriction improves ventilation in COPD
The concept that low-carb diets are better tolerated in individuals with chronic lung disease is not just a mechanistic theory. Studies support it as well.
A randomized, double-blinded study in a metabolic unit compared the effects of diet over the course of five days. Investigators randomly gave COPD patients diets consisting of low-, moderate-, and high-carbohydrate content (28%, 53%, and 74% carbohydrate, respectively) and measured the effects on respiratory function.
Subjects on the low-carb diet had significantly lower carbon dioxide production, lower RQ, and lower levels of carbon dioxide in the blood compared to those consuming higher-carbohydrate diets. These findings suggest the lower-carb diet resulted in improved lung function.
Whether carbohydrate restriction results in decreased morbidity and mortality from COPD is not yet known. However, even small improvements in ventilation in patients with COPD from a low-carb diet may be clinically relevant for those who are at risk for respiratory failure.
5. Low-carb diets and the mechanics of breathing
For individuals with lung disease, there are additional benefits of carbohydrate restriction related to the work of breathing.
In the setting of an exacerbation of lung disease, breathing suddenly becomes the number one priority. Patients in respiratory distress often don't feel hungry, may be too lethargic to eat, or may have mechanical barriers to eating, such as an oxygen mask or BiPAP mask in place.
Their situation may be so delicate that even temporary removal of the mask would be risky. Smaller, more nutritious meals may be preferable in order to meet the patient's energy needs and allow sufficient rest between meals.
Carbohydrate-restricted diets focus on providing essential nutrients, especially protein, which is particularly important when patients are recovering from an illness.
Patients whose food intake is limited also need energy-dense foods, and fat provides more than twice as much energy per gram as carbohydrate, without raising blood sugar levels. Thus, a carbohydrate-restricted diet could supply smaller-volume meals with increased calorie and nutrient density. This could be important when every bite matters.
6. Evidence: diet and asthma
In 1930, researchers selected 15 children (ages 3-15 years) with severe, chronic asthma who did not respond to conventional treatment for a trial of a low-carbohydrate, ketogenic diet.The diet progressed from a what is roughly a fat:carb ratio of 1:1.5 in the beginning to a ratio of 3:1.
At the end of the third week, 14 of 15 children showed moderate or marked improvement in their asthma. These improvements were maintained for two months, and several children continued to participate with moderate to marked improvement for up to 10 months.
While this study showed great promise, there has not been subsequent published research on the role of low-carbohydrate diets in asthma.
There is, however, a randomized controlled trial that compared a Mediterranean diet that included fatty fish consumed twice weekly (intervention) with the usual diet (control) in children with mild asthma. Children in the intervention group were found to have decreased bronchial inflammation and decreased medication use.
Given the lack of high-quality research studies, there is no good evidence at this time to recommend for or against any particular eating pattern in asthma.
7. Evidence: high fat supplemental feeding in critical care
Individuals who suffer severe or complex lung disease may require mechanical ventilation in a critical care setting, such as the intensive care unit.
Since these patients are intubated (in other words, they have a tube inserted in the airway) and usually sedated, they are not able to eat and instead are given either enteral nutrition (tube feedings, delivered into the stomach) or total parenteral nutrition (TPN), which is delivered intravenously.
In trials of critically ill patients, tube feeding with a low-carb, high-fat solution was superior to standard, high-carbohydrate formulas, as measured by a lower carbon dioxide concentration in the blood and significantly shorter durations of mechanical ventilation.
In fact, the high-fat group spent an average of 62 hours less on the ventilator in two separate studies.
TPN formulas that are mostly glucose are associated with significant increases in carbon dioxide production and increased respiratory effort to remove it. When compared with patients receiving a large percentage of fat in their TPN formula, patients receiving glucose produced significantly more carbon dioxide.
There are even published case reports of individuals developing respiratory failure within hours after being started on high-carbohydrate TPN. It is theorized that the large carbohydrate load increased carbon dioxide production, which led to the rapid respiratory failure.
8. Evidence: use of supplements in COPD
Nutrition supplements are a standard intervention utilized by dietitians to correct malnutrition in patients, as supplements are calorie-dense and easy to consume.
However, one study showed that standard high-carbohydrate supplements caused an increase in carbon dioxide load and a decrease in exercise tolerance compared to lower-carb, higher-fat supplements with the same caloric content. Another study has shown that use of high-fat supplements is associated with improved lung function in patients with COPD.
A review of supplementation with specific nutrients showed that a variety of dietary interventions are associated with improvements in COPD patients:
- omega-3 fatty acids are associated with decreased inflammatory markers
- essential amino acids are associated with increased lean body mass, strength, and cognitive function
- vitamin D is associated with a reduced risk of COPD exacerbations
- antioxidant vitamins, selenium, calcium, chloride, and iron are independently associated with a higher volume of air that can be forced out in one second after taking a deep breath (called "forced expiratory volume in 1 second" or FEV1)
It is impossible to draw conclusions from such correlational studies, however, because the baseline diet, which could vary drastically among patients, is a large confounding variable.
Perhaps the most important takeaway regarding supplements is that high-fat supplements are an option to correct malnutrition without causing potential negative respiratory side effects that have been identified with standard, high-carb supplements.
9. Conclusion
A low-carb dietary intervention may be an important, under-utilized tool in treating asthma and COPD due to its beneficial effects on glycemic control, carbon dioxide production, and inflammation. Moreover, it is nutrient dense and therefore may improve the nutritional status of those with COPD.
Numerous studies have documented the effects of low-carb diets improving lung function in patients with lung disease, both in acute and chronic disease states. It is now important to understand whether this biochemical advantage translates into improvement in clinical status and reductions in morbidity and mortality.
For patients with limited ventilatory reserve, even a small improvement in lung function may be clinically relevant. In addition, the anti-inflammatory and glucose-lowering effects of eating low carb have been well-documented.
Therefore, for patients who are in a borderline situation and at risk for respiratory failure, the advantages that come with a low-carb diet may be particularly meaningful.
These advantages over the standard approach to managing lung disease make low-carb diets a potential powerful adjuvant therapy for individuals with lung disease.
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