Roflumilast

Potential Health Benefits of Roflumilast

• Treats COPD (Chronic obstructive pulmonary disease) [1-20]
• Treats asthma [21-31]
• Improves cognitive function [32-49]
• Reduces overall body fat [13-20, 50-53]
• Maintains bone strength and quality [54]
• Improves blood sugar levels [51, 55-60]
• Improves bladder function [61-62]
• Treats and prevents cancer [63-71]
• Decreases alcohol consumption [72-73]

What is Roflumilast?

Roflumilast is a drug that acts as a selective, long-acting inhibitor of the enzyme phosphodiesterase-4. It works by reducing the swelling in the lungs. It is commonly used for the treatment of severe chronic obstructive pulmonary disease (COPD), a group of diseases that affect your lungs and airways.

How Roflumilast Works?

Roflumilast works by inhibiting an enzyme called phosphodiesterase 4 (PDE4) which in turn prevents the breakdown of cyclic adenosine monophosphate (cAMP) into its inactive state (called AMP). This process decreases cell inflammation, inhibits fibrosis (thickening or scarring of the tissue), and relaxes the smooth muscle in the lungs.

Chemical Structure of Roflumilast

Research on Roflumilast

A. Treats COPD (Chronic Obstructive Pulmonary Disease)

By inhibiting the enzyme phosphodiesterase 4 (PDE4), roflumilast decreases cell inflammation, inhibits fibrosis (thickening or scarring of the tissue), and relaxes the smooth muscle in the lungs. An overwhelming number of studies support the benefits of roflumilast in patients with COPD:

1. A review of studies showed that roflumilast was safe and effective in treating COPD. [1]
2. In patients with severe to very severe COPD associated with chronic bronchitis, roflumilast was effective in preventing the worsening of the condition (exacerbation). [2]
3. In COPD patients, roflumilast successfully shifted the patients to a more stable state. [3]
4. In patients with severe COPD and chronic bronchitis, roflumilast reduced the worsening of the condition and lowered the frequency of hospitalizations. [4]
5. In COPD patients with a high risk of exacerbations, roflumilast administration prevented the worsening of symptoms. [5]
6. A review of studies found that roflumilast improved lung function and reduced exacerbations among COPD patients via inhibition of airway inflammation. [6]
7. A study showed that roflumilast was safe and effective for controlling COPD exacerbations. [7]
8. In severe COPD patients not controlled by inhaled combination therapy, the addition of roflumilast reduced the prevalence of exacerbations. [8]
9. In Asian COPD patients, roflumilast played an important role in improving lung function. [9]
10. A review of studies confirmed the benefits of roflumilast in reducing the incidence of exacerbations in COPD patients. [10]
11. In Korean COPD patients, roflumilast significantly improved lung function with a tolerable safety profile. [11]
12. In chronic obstructive pulmonary disease (COPD) patients, roflumilast treatment resulted in improvements in exercise tolerance. [12]
13. In patients with severe airflow limitation, bronchitic symptoms, and a history of COPD exacerbations, the administration of roflumilast was associated with significant improvements in measures of lung function. [13-20]

B. Treats Asthma

Evidence suggests that roflumilast’s ability to inhibit airway inflammation can produce beneficial effects in patients with asthma (narrowing and swelling of the airways):

1. In asthma patients, roflumilast attenuated allergen-induced bronchoconstriction (narrowing of the airways) by reducing the levels of inflammatory mediators such as eosinophils and neutrophils. [21]
2. In asthmatic patients, the administration of 100, 250, and 500 micrograms of roflumilast once daily for 12 weeks resulted in significant improvements in morning and evening peak expiratory flow (a measure of lung function). [22]
3. A review of studies showed that roflumilast was well tolerated by asthma patients and was associated with symptom relief. [23]
4. In patients with mild to moderate asthma, roflumilast significantly improved the symptoms. [24]
5. A review of studies showed that roflumilast can help treat asthma through its anti-inflammatory properties. [25]
6. In asthmatic mice, the combined treatment with roflumilast and fluticasone significantly improved the symptoms of asthma. [26]
7. In a murine model of chronic asthma, roflumilast produced beneficial effects by regulating airway inflammation, airway hyper-responsiveness (AHR), and airway remodeling. [27]
8. A study showed that roflumilast can help treat the symptoms of COPD and asthma. [28]
9. In patients with moderate-to-severe asthma, the combined treatment of roflumilast with montelukast resulted in improved lung function and asthma control. [29]
10. In asthmatic patients, daily oral administration of roflumilast was effective in improving pulmonary function and asthma symptoms. [30]
11. In patients with mild asthma, roflumilast attenuated allergen-induced AHR. [31]

C. Improves Cognitive Function

Numerous studies found that roflumilast has the ability to improve cognitive function and protect against brain disorders:

1. In rats with subarachnoid hemorrhage (bleeding in the space between the brain and the surrounding membrane), roflumilast administration significantly improved neurological deficits. [32]
2. In a mouse model of Alzheimer’s disease (AD), roflumilast significantly ameliorated cognitive impairment. [33]
3. In mice with insufficient blood flow to the brain, roflumilast demonstrated neuroprotective effects by decreasing nerve inflammation. 34]
4. In rodents, roflumilast improved memory compared to rolipram, an anti-depressant. [35]
5. In aged rats subjected to chronic cerebral hypoperfusion (decreased blood flow to the brain), roflumilast promoted memory recovery and attenuated white matter injury. [36]
6. In rat middle cerebral artery occlusion (MCAO) models, roflumilast prevented ischemic stroke-induced neuronal damage by reducing oxidative stress. [37]
7. In AD mice, roflumilast was successful in improving learning and memory. [38]
8. In rats, the combined administration of roflumilast and tadalafil resulted in memory enhancement. [39]
9. In rats with transient global cerebral ischemia (TGCI), roflumilast exhibited protective effects against TGCI-induced memory impairments. [40]
10. In schizophrenia patients (a mental disorder that affects thinking, emotion, and reality perception), roflumilast treatment resulted in significant improvement in verbal memory. [41]
11. In rats, roflumilast ameliorated hypertension-induced learning and memory impairments. [42]
12. In AD mice, roflumilast was effective in alleviating memory loss and depression. [43]
13. In juvenile rats, roflumilast reduced cellular damage in the brain caused by cerebral ischemia/reperfusion injury. [44]
14. In rat brains, roflumilast significantly decreased elevated pro-inflammatory cytokines like TNF-a, IFN-?, and NF-?B. [45]
15. In healthy young humans, roflumilast was potentially effective for treating disorders affected by disrupted sensory gating. [46]
16. In patients with schizophrenia, roflumilast treatment was associated with improvement in attention. [47]
17. In young and elderly humans with acute brain injury, roflumilast treated residual cognitive deficits. [48]
18. In rats, roflumilast prevented memory deficits caused by sleep deprivation. [49]

D. Reduces Overall Body Fat

Studies also show that roflumilast can help promote weight loss in overweight and obese people:

1. In patients with COPD, roflumilast administration was associated with weight loss. [13-20]
2. In obese adults with prediabetes, roflumilast was associated with fat mass loss. [50]
3. In mice, roflumilast administration resulted in the reduction of body weight gain. [51]
4. A study showed that roflumilast can help address obesity-related diseases by suppressing the formation of fat cells. [52]
5. In obese women with polycystic ovary syndrome (PCOS), short-term monotherapy with roflumilast was associated with significant weight loss. [53]

E. Maintains Bone Strength and Quality

Evidence also found that roflumilast can help protect against bone loss:

1. In rats with ligature-induced periodontitis (inflammation of the gums and bone surrounding and supporting the teeth), roflumilast was found to decrease alveolar bone loss. [54]

F. Improves Blood Sugar Levels

A number of studies found that roflumilast is beneficial in diabetic patients due to its ability to lower elevated blood sugar levels:

1. In mice fed with a high-fat Western-type diet, roflumilast treatment reduced weight gain by increasing energy expenditure and led to improved glucose metabolism. [51]
2. In type 2 diabetes mellitus (T2DM) patients, roflumilast administration resulted in lower blood sugar levels. [55]
3. In mice, oral administration of roflumilast successfully delayed the progression of diabetes. [56]
4. In COPD patients with comorbid type 2 diabetes mellitus, roflumilast treatment improved results in tests that measure blood sugar levels such as fasting blood glucose and hemoglobin A1c (glycated hemoglobin). [57]
5. In diabetic rats with elevated blood sugar levels, roflumilast administration at 2 and 3 mg/kg protected against diabetic nephropathy (kidney damage). [58]
6. In patients with newly diagnosed type 2 diabetes mellitus, roflumilast administration at a dose of 500 µg once daily resulted in a greater reduction in glycated hemoglobin. [59]
7. In patients with COPD with metabolic syndrome, long-term administration of roflumilast in addition to traditional treatment improved blood sugar levels. [60]

G. Improves Bladder Function

Studies found that roflumilast can help improve the function of the bladder (a hollow, muscular, balloon-shaped organ that holds urine) and address bladder disorders:

1. In rats with diabetic bladder dysfunction, oral treatment with roflumilast for 6 weeks improved bladder function and inhibited the production of inflammatory factors. [61]
2. In rats with obesity-associated overactive bladder, roflumilast treatment for 12 weeks restored normal bladder function via inhibition of bladder inflammation. [62]

H. Treats and Prevents Cancer

Strong scientific evidence suggests that roflumilast has the ability to suppress the growth of tumors and cancer cells:

1. In a murine lung cancer model, roflumilast inhibited the growth of lung cancer cells. [63]
2. A cell study showed that roflumilast inhibited ovarian cancer cell growth and spread by inducing apoptosis (programmed cell death) and cell cycle arrest. [64]
3. In lung cancer patients, combination treatments with roflumilast and anti-cancer medications produced increased apoptosis. [65]
4. In patients with cancer of the lymphatic system, the addition of roflumilast to chemotherapy was associated with increased inhibition of cancer cells and improved survival rate. [66]
5. A cell study found that roflumilast enhanced the sensitivity of ovarian cancer cells to the chemotherapeutic agent cisplatin. [67]
6. In rats with prostate cancer, roflumilast enhanced the cytotoxic and apoptotic effects of cisplatin. [68]
7. In rats with colon cancer, roflumilast restored the normal architecture of the colonic mucosa via inhibition of inflammation and oxidative stress. [69]
8. In patients with advanced beta cell malignancies, the administration of oral roflumilast at a dose of 500 mcg daily for 21 days with prednisone on days 8 to 14 inhibited the growth and spread of cancer cells. [70]
9. In patients with liver cancer, roflumilast suppressed the progression of cancer cells. [71]

I. Decreases Alcohol Consumption

Studies found that roflumilast can help suppress the urge to drink alcoholic beverages, suggesting that it can be beneficial in the treatment of alcohol addiction:

1. In a mouse model of alcoholism, roflumilast treatment decreased ethanol intake and preference. [72]
2. In mice with alcoholism treated with roflumilast (1, 3, or 10 mg/kg), a significant reduction in ethanol intake and preference was observed. [73]

Associated Side Effects of Roflumilast

Roflumilast side effects are very uncommon. There have been some side effects associated with the use of this drug wherein the patient had one of the issues listed below at some point while being on roflumilast. However, these side effects weren’t confirmed to be associated with the treatment and could have been a coincidence and not related to the use of roflumilast. Despite this, it was listed as a side effect associated with roflumilast even though these associated side effects are very uncommon.

Side effects associated with roflumilast may include the following:

• Abdominal pain
• Diarrhea
• Loss of appetite
• Muscle pain
• Nausea
• Palpitation

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