Idiopathic Pulmonary Fibrosis - a comprehensive health approach

Idiopathic pulmonary fibrosis

What is pulmonary fibrosis? Simply stated, it is advanced scarring of the lung.  And idiopathic means “we don’t know what causes it”.  One of the main genetic underpinnings and risk factors of pulmonary fibrosis is a genetic mutation in TERT and TERC, which are needed for Telomerase, the major enzyme in the repletion of telomeres.  Telomere length maintenance is essential for cells to continue functioning properly.  When telomeres become very short, there is apoptosis or “cell death” and short telomeres are associated with advanced aging or premature aging.  The classic signs of short telomere disease are early graying of hair, fingernail dysplasia, bone marrow failure, pulmonary fibrosis and idiopathic liver disease/cirrhosis.  Only a small percentage of patients with pulmonary fibrosis have genetic mutations in the telomerase pathway, but the pathophysiology has taught us much about IPF.

What does this genetic knowledge teach us about pulmonary fibrosis?  Essentially, that IPF is advanced aging of the lung. 

Pirfenidone/Esbriet and Nintedanib/Ofev, were the first medications to be approved by the FDA in the United States, in 2014.   Prior to these medications, there were essentially no approved effective therapies for IPF.  However, if tolerated, the best outcome is that these medications stall the progression of the disease.  There are many other medications in trial phases for IPF, but historically, less than 5% of medications in clinical trials come to fruition and are approved.

What else can be done?

Is diet important?

Have you seen Super-Size Me? If not, consider watching it and there’s no doubt that a poor diet accelerates aging and disease.  The protagonist ate every meal at McDonald’s for 30 days and it wreaked havoc on his health.  It took months to restore his health to normal.  For some people, their liver is sensitive to a poor diet, for others, it’s their lungs.  What is a healthy diet?  Mostly plants, vegetables and 1-3 servings of fruit/day, using meat as a garnish, getting plenty of Omega 3s (fatty fish like salmon, sardines, etc, walnuts, chia, flax seed, olive oil), and little or no processed food or sugars.  Alcohol in moderation, red wine preferred for its low glycemic index.  Ask your doctor is you should be on a special diet.   Some people have food sensitivities they do not yet know about. Testing can be done for them.  The Core Food Plan is available to functional medicine practitioners.  Ask your doctor is you want a copy of the plan.

The link below is an introduction to eating for healthy aging.

https://sharonpalmer.com/2012-04-17-eating-for-healthy-aging/

Dr. Bredesen has done some amazing work in cognitive decline and reversal of Alzheimer’s disease. What do all patients with Alzheimer’s have in common?  They’re of an advanced age.  You’ve never heard of a patient with Alzheimer’s who’s 25 years old.   The science behind his diet makes a lot of sense for anti-aging.  His diet is called the 12/3 Ketoflex diet.  12: Fast for 12 or more hours per day.  If you eat dinner at 8:00 PM and finish at 8:30 pm, no snacking before bed, and the earliest you’d want calories the next morning would be 8:30 AM or later.  3: eat no more than 3 hours before bed without evening snacking – eat at 6:00 pm – bed at 9:00.   Keto – means achieve mild ketosis. This does not mean a “ketogenic” diet which is high in meat and fat, but it is mostly plant based, and goal is to achieve mild ketosis.  The intermittent fasting helps with that.  The “flex” means that the diet can be achieved in carnivores and vegetarians alike.

Stop smoking.  This is very important.  The number 1 modifiable lifestyle factor increasing risk of PF is tobacco smoking.

Exercise.  There are great pulmonary rehab programs.  There is a really interesting program designed by a doctor of exercise therapy that is available and I find his work fascinating.  Dr. Noah Greenspan.  If you’re interested, the link to his exercise chapter is here:  https://www.pulmonarywellness.com/book/7-exercise/.   His book is entitled “Ultimate Pulmonary Wellness”.  There is also a yoga program breathing exercise found to increase lung function.

Other options:

Pirfenidone/ Esbriet or Nintedanib/ Ofev. These 2 medications are FDA approved to treat IPF.

DHEA.  This is a pre-hormone that is converted to active hormones down-stream.  Deficiency in DHEA can lead to testosterone and estrogen deficiencies.  DHEA progressively becomes lower with age.  However, it’s been shown that in patients with pulmonary fibrosis, there are significantly lower levels than age matched controls without PF. Additionally, DHEA has been shown to be antifibrotic.  (https://www.ncbi.nlm.nih.gov/pubmed/23143540).  I think this data supports at least considering DHEA support to normalize levels in PF.

NAC/ Glutathione.  We used to prescribe NAC to all patients with IPF before the PANTHER-IPF trial was released, which showed no benefit above control group. However, there were major problems with that clinical trial making outcome of results questionable.  There were positive observational trials published prior to the PANTHER-IPF. It clearly helps some patients.  However, there is a subset of people who do not effectively convert NAC to Glutathione, and in these cases giving Glutathione directly may be best.  There has been one study showing sublingual glutathione is more bioavailable than orally administered glutathione.

B vitamins may be needed if problems with Methylation or elevated homocysteine levels. Goal homocysteine 6 or lower.

Hormone normalization/restoration.  With aging, important pro-hormones (DHEA, pregnenolone) and end hormones (estrogen and testosterone) decrease over time, some more abruptly than others (total hysterectomy).  Hormone replacement therapy has to be carefully considered as there is association with increasing risk of hormone related cancers such as prostate and breast cancer.  Consideration for bio-identical hormones should be considered.

Vitamin C (goal >1.3). Antioxidant, and helps protect degradation of glutathione.

Vitamin E (goal 12-20).  As with most vitamins and minerals, it is best to get them from food, which with vitamin E, is pretty easy to do.  There is some risk associated with supplementing vitamin E.   Only one ounce of sunflower seeds gives you 66% of your daily dietary needs.  Almonds, hazelnuts, avocados, and many fish are also rich in vitamin E.

There may be other options to consider. Talk with your doctor about clinical trials and what other treatments may be available.

The below reference guide was taken from Dr. Bredesen’s work in reversing Cognitive decline and Alzheimer’s but think it has direct application in any disease of premature aging, including IPF.   Optimal health markers are below.  Through dietary and supplemental changes, all these levels can be normalized, and age-related disease significantly improved.  Consider talking to your doctor about having these parameters assessed.   You may need to see a functional medicine or integrative medicine specialist to address these.

      Vitamin B12 level, goal 500-1500

      Folate level, goal 10-25

      Vitamin B6 level, goal 60-100

      Fasting insulin, goal </= 4.5

      Fasting glucose, goal <90

      Hemoglobin A1C, goal <5.6

      Hs-CRP <0.9 mg/dL

      Omega 6/ Omega 3 ratio, goal 0.5-3

      Vitamin D3, goal 50-80 ng/mL

      Vitamin C, goal 1.3-2.5

      Vitamin E, goal 12-20

      Thyroid studies

   fT3, goal 3.2-4.2 pg/mL

   fT4, goal 1.3-1.8 pg/mL

   rT3, goal <20 ng/dL

   TSH, goal <2.0 mIU/mL

   fT3/rT3 ratio, goal >= 20

      Morning cortisol 10-18 mcg/dL

      Pregnenolone 50-100 ng/dL

      DHEA-S, goal 350-430 mcg/dL (F), 400-500 mcg/dL (M)

      Zinc, goal 90-110 mcg/dL or RBC zinc 12-14 mg/L

      Copper: Zinc ratio, goal 08-1.2

      Copper – 3 x Ceruloplasmin, goal <= 30

      RBC Magnesium 5.2-6.5 mg/dL

      Selenium, goal 110-150 ng/mL

      Glutathione, goal 800 – 1230 micromolar (5.0-5.5)

      Cholesterol: LDL-p (LDL particle number) goal 700-1000 or sdLDL (small dense LDL) <20 mg/dL or <20% of LDL. Or oxidized LDL <60. Total chol >150. HDL chol >50, triglyceride <150

      Sex hormones

   Estradiol, goal 50-250 pg/mL (F)

   Progesterone, goal 1-20ng/mL (F)

   Estradiol: progesterone, goal 10-100 (F)

   fTestosterone, goal 6.5-15ng/dL (M)

   Total testosterone, goal 500-1000 ng/dL (M)

      Potassium, goal 4.5-5.5

      Calcium, goal 8.5-10.5

      Vitamin E, measured as alpha-tocopherol, goal 12-20 mcg/mL

      Thiamine, goal 20-30

Written by: Leann Silhan, MD