A new study entitled “Vitamin D and Chronic Lung Colonization in Pediatric and Young Adult Cystic Fibrosis Patients” published in the Spanish-language journal Nutrición Hospitalaria, investigated vitamin D levels in the body and its association with chronic lung colonization. The study showed that vitamin D supplements did not improve the vitamin’s insufficiency in young cystic fibrosis patients.
Cystic fibrosis (CF) is a frequently inherited genetic disorder in the Western world, and most CF patients develop respiratory failure due to chronic pulmonary infection. Several factors, including environmental, nutritional, and socioeconomic, may affect the clinical manifestations of cystic fibrosis. Low levels of vitamin D are highly prevalent in CF patients, likely due to the combination of inadequate nutrient absorption, impaired metabolism, and lack of sun exposure. Vitamin D insufficiency is associated with high incidence of bone disease or osteoporosis in CF patients.
In this study, researchers evaluated vitamin D levels in serum samples from 377 cystic fibrosis patients whose ages ranged from 2 months to 20 years. The patients, from several university hospitals in Spain, were evaluated over the course of two years. The researchers found that younger patients had lower levels of vitamin D as well as a higher number of pathogen colonizations. They showed that despite CF patients receiving vitamin D supplements — which are currently recommended for the disease — a high percentage showed insufficient levels of the vitamin. Moreover, they found that age, pancreatic function, type of diagnosis, and lung colonization modulate the levels of serum vitamin D in these patients. Regardless of age, diagnosis by screening or pancreatic status, chronic colonization by Pseudomonas aeruginosa in children and adolescents and by Staphylococcus aureus in infants and preschoolers increased their risk of developing vitamin D deficiency.
The authors, however, are aware of the limitations of their study. The longitudinal nature of the study makes impossible to know whether vitamin D levels are the cause or consequence of chronic lung colonization in these patients. The multicenter nature of the study, while necessary to obtain a sample size sufficient in low-prevalence diseases as CF, could introduce biases when analyzing the dose and vitamin D levels due to lack of vitamin supplement standardization protocol among the centers. However, all patients received vitamin D doses as expected. The clinical centers were from different latitudes, but the sera vitamin D were collected during the same time period (fall-winter), decreasing but not eliminating the modifying effect of sun exposure on vitamin D levels.
These findings could encourage additional studies into the interplay of vitamin D, cystic fibrosis, and bacterial infections. New discoveries might help physicians develop new best practices for supplements that could better optimize vitamin D levels in CF patients.
What can you do?
How about ensuring you and your family have 2 serves of oily fish a week – try baked salmon or a tuna sushi roll?
How about serving eggs a couple of times a week – try an egg & cheese wrap for brekky or sneaking an egg into their mash at dinnertime?
You can see the original article here CFRI
Once upon a time there was a CF mother who was looking for anything that might help her son with CF. Sound familiar?
For those of you not familiar, Dr. Valerie Hudson’s foray into CF research began after her son, John, now 6, was diagnosed with cystic fibrosis as a baby. In her desperation, she taught herself anatomy from her older son’s high school anatomy textbook and began her long journey into the field of CF research. As the years passed, she became intrigued with the chemical glutathione and its role in the cell. After coming to believe that this chemical could make a difference in the health of her sons, Dr. Hudson eventually recruited Dr. Bishop to run a small, preliminary study using inhaled glutathione. Dr. Hudson presented their results.
Glutathione (GSH) is a tri-peptide, a very small protein, present throughout our bodies, but it appears in especially high concentrations in the epithelial lining fluid of the lungs.(Epithelial cells are the cells that line the inside of our lungs and they produce this fluid.) When the body has to deal with high levels of free radicals and oxidative stress, as is the case in CF lungs, the body provides higher levels of GSH to help it cope. GSH has several properties. It is a natural mucolytic. It helps regulate the immune response, as both an anti-inflammatory and as a cell-signaling molecule directing the white blood cells as to where and what to fight. It scavenges free radicals, and it is an anti-oxidant. Additionally, oxidized GSH protects proteins during stressful events in the lungs.
There is significant evidence of the importance of GSH in CF pathophysiology. At the 2000 CFRI Conference, you may have heard Dr. Rabin Tirouvanziam give an update on his GSH research. Dr. Bishop reported on a more recent study that showed that normal mice lung cells, when challenged with Pseudomonas aeruginosa, increase levels of epithelial lining fluid GSH six-fold to help fight the infection. By contrast, CF mice have significantly lower levels of a GSH response. This response is severely reduced in people with CF as well.
Dr. Bishop presented his small-scale, preliminary trial using inhaled glutathione. The GSH used was “pharmaceutical grade of 98.6 percent,” it was buffered and diluted to minimize irritation, and it was tested and found free of bacterial and fungal products. He also relied on the results from seven other published human trials, which observed no significant adverse events when used. In his randomized, placebo-controlled, double blind, clinical trial of inhaled GSH, Dr. Bishop recruited 19 subjects. Ten used the inhaled GSH and nine used the placebo. The age range of the subjects was from six to eighteen, and the trial occurred during the summer months. Patients inhaled through a mask nebulizer approximately 66 milligrams per kilogram of their body weight of GSH mixed with sterile water, divided into four daily inhalations sessions, each three to four hours apart.
The results of this clinical trial showed significant improvement in 11 out of 13 factors measured before and after use of GSH, including peak flow, overall improvement in health, and reduced cough. Dr. Bishop is the first to recognize the limitations of his trial (size is a significant factor), while drawing the following conclusions. GSH deficiency in epithelial lining fluid may play a major role in pathogenesis of CF, and GSH inhalation therapy appears to be effective for CF.
Dr. Bishop issued a clear caution to parents and adults with CF that further research still needs to be done before this can be considered a legitimate therapy for the CF community. Further research needs include a large, multi-centered clinical trial, the use of an FDA-approved product, and methods to increase convenience and control of administering the product. (Patients had to prepare their own solutions using capsules and sterile water, so doses were hand-prepared. This is time-consuming and dosages are not necessarily exact). Additionally, Dr. Bishop urged clarification of the route of delivery (oral vs.inhaled), dosage specifications, schedule of administration of the drug, patient selection, and other GSH augmentation tactics. Dr. Bishop warned that this is an experimental therapy not approved by the Cystic Fibrosis Foundation. No long-term studies have been done to ensure safety and efficacy of GSH use. He further cautioned his audience that the CFF recommends not using this GHS inhalation therapy until further studies are done.
The best pre-cursor on the market that is readily available as an oral dose seems to be NAC
- N-Acetyl-Cysteine (NAC)
It is derived from the amino acid L-Cysteine, and acts as a precursor of glutathione. NAC is quickly metabolized into glutathione once it enters the body. It has been proven in numerous scientific studies and clinical trials, to boost intracellular production of glutathione, and is approved by the FDA for treatment of accetaminophen overdose. Because of glutathione’s mucolytic action, NAC (brand name Mucomyst) is commonly used in the treatment of lung diseases like cystic fibrosis, bronchitis and asthma.
When we asked around about this a few years ago it seemed that it was destined to remain a sideline alternative treatment – with the initial pilot research driven by a CF mother and a Dr Bishop out of a Utah in 2004. However, since then other research groups have been cautiously exploring the potential benefits. We know that the Royal Children’s Hospital in Melbourne are now looking at it as part of a nutritional review and Standford University have just released a paper on it which I have posted below.
You can read about the original study here: http://uvicf.org/researchnewsite/glutathionenewsite/protocol.htm
By the way if you’re keen, you can buy the oral cysteine “Fizzy NAC” online here: http://www.bioadvantex.com/us/catalogsearch/result/?q=fizzy+nac
Glutathione is a very simple molecule that is produced naturally all the time in your body. It is a combination of three simple building blocks of protein or amino acids — cysteine, glycine and glutamine. The secret of its power is the sulfur (SH) chemical groups it contains. Sulfur is a sticky, smelly molecule. It acts like fly paper and all the bad things in the body stick onto it, including free radicals and toxins like mercury and other heavy metals. But that’s not all. Glutathione is also critical in helping your immune system do its job of fighting infections and preventing cancer. That’s why studies show that it can help in the treatment of AIDS and MS. It is critical for immune function and controlling inflammation. It is the master detoxifier and the body’s main antioxidant, protecting our cells and making our energy metabolism run well.
What’s glutathione got to do with CF?
Glutathione first seemed to come into the limelight relating to CF in 1997 when Valerie Hudson worked with Dr Clark Bishop (CF Clinic in Salt Lake city Utah) to undertake the first trial using glutathione (GSH) to help her 2 young boys who both had CF. Its a great example of the fact that no one is more dedicated than the parents of a child with a chronic illness or disease. You might like to check out the article here:
Article : A mothers fight against CF
In this issue of CHEST, Dr Bishop and colleagues report encouraging results from a small, double-blind, placebo-controlled clinical trial of inhaled glutathione in patients with cystic fibrosis. The rationale for this therapy lies in previous data reporting that glutathione levels in the lung epithelial lining fluid of patients with cystic fibrosis are low,1and that cystic fibrosis lung disease is associated with increased oxidative damage.2In addition, more recent studies3–6 have also demonstrated that the cystic fibrosis transmembrane conductance regulator (CFTR), which is defective in cystic fibrosis, regulates a substantial portion of glutathione efflux into the epithelial lining fluid.
The thinking has since shifted to N-acetylcysteine (precursor to gluathione synthesis) as a more effective way to support the body in generating gluathione on its own.
1] In 2006, stanford university started to investigate N-acetylcysteine for CF. – They did a small randomised placebo controlled, double blind efficacy study investigating NAC on lung inflammation in CF and two of the professors applied for a patent with regards to gluathione being used as a treatment for pulmonary lung disease.
2] Standford university professors then trialled NAC for use with Autism (2012) as they believe it increases the capacity of the body’s main antioxidant network.
The jury is out on whether glutathione is offering any real benefit but clearly there are lots of parents out there who are still trialling it as a supplement.
What about you? Have you tried glutathione with your child and can you guestimate as to whether its made any difference?
What’s the deal with fish oil and cystic fibrosis?
Fish oil is used for several conditions including heart disease, reducing triglycerides (blood fats), diabetes, rheumatoid arthritis, ADHD, Crohn’s disease, cystic fibrosis and asthma. Studies have shown it may reduce blood pressure and be helpful in diabetes, rheumatoid arthritis, Crohn’s disease and cystic fibrosis, although better studies are needed.
The impaired digestion of fats in CF often leads to a deficiency of essential fatty acids (EFAs). This deficiency may in turn lead to a lowered immune function, which makes children with CF more susceptible to respiratory infection. EFA deficiency can be reversed by supplementation with corn oil (1 gram per 2.2 pounds [1 kg] body weight per day), safflower oil (1 gram per 2.2 pounds [1 kg] body weight per day), linoleic acid (7.7 grams per day), and eicosapentaenoic acid (EPA from fish oil) (2.7 grams per day). EPA supplementation was particularly effective. In a double-blind trial, six weeks of supplementation with 2.7 grams per day of EPA led to reduction in sputum and improvement in lung function in children with chronic respiratory infection due to CF.
When questioned, all the research team at the Sydney Children’s Hospital can tell us is that “Yes fish oil has been shown to be advantageous when used on mice…”. If you read the research to date there has been some evidence that fish oil can have a positive effect but like many parents of children with chronic illness, even if there’s no proof, should we be trying it anyway? Below is a quick summary of the mouse study:
Recently, a reversible fatty acid imbalance, i.e., elevated AA and low DHA that may underlie the chronic lung and pancreatic lesions of CF, was demonstrated in a mouse model of the human disease. Oral administration of high doses of DHA not only corrected the membrane lipid imbalance but also reversed the signs of CF in the affected mice. In addition to this theoretical basis for possible dietary therapeutic interventions, a recent Cochrane review concluded that, Regular n-3 supplements may provide some benefits for CF patients with relatively few adverse effects but cautioned that the evidence, so far, is insufficient to draw firm conclusions (8). Improvement of pulmonary function (e.g., FEV) has been observed in CF patients after 6-week to 8-month treatments with n-3 LCP including both EPA and DHA. The extent to which improvement was related to the combination of EPA and DHA versus DHA alone requires additional clarification, but recent observations suggest an independent effect of DHA. Effective doses of fish oil range from 4.5 to 5.3 g/d, providing 2.7 to 3.2 g/d of EPA and 1.8 to 2.1 g/d of DHA, but few other doses were evaluated.
And it seems that researchers at the University of Sydney agree that fish oil helps cystic fibrosis patients
NEW SOUTH WALES, AUSTRALIA. Researchers at the University of Sydney have found that daily supplementation with fish oil capsules alleviates many of the symptoms of cystic fibrosis. Cystic fibrosis is a serious, inherited childhood disease which involves a malfunctioning of the body’s mucus glands. An abnormally thick mucus is produced which clogs the lungs and results in breathing difficulties. Other symptoms include persistent cough and wheezing, repeated lung infections, and a failure to gain weight. Sixteen cystic fibrosis patients aged 12 to 26 took part in the experiment. Half the group received fish oil capsules providing 2.7 g of eicosapentaenoic acid (EPA) per day while the other half received identical olive oil capsules as a placebo. After six weeks of treatment the patients receiving EPA coughed up significantly less sputum, were breathing easier (both forced expiatory volume and vital capacity were up) and generally felt better. The Australian researchers believe that the EPA acts by modifying the role of leukotriene B4. Leukotriene B4 is thought to be the main culprit in the excessive inflammatory response to bacteria which characterizes cystic fibrosis.
Source: Lawrence, R. and Sorrell, T. Eicosapentaenoic acid in cystic fibrosis: evidence of a pathogenetic role for leukotriene B4. The Lancet, Vol. 342, August 21, 1993, pp. 465-69
And even though CFers have trouble with fat absorption; some [minor] research shows that CFers are able to successfully absorb omega-3s effectively by mouth.
Researchers at the State University of Gent set up an experiment to see if CF patients are able to absorb omega-3s effectively by mouth. The trial involved 9 CF patients (4 females and 5 males) ranging in age from 7 to 20 years. All had been diagnosed with pancreatic insufficiency and had poor fat absorption despite supplementing with pancreatic enzyme preparations. The patients were assigned to receive either 6 fish oil capsules per day for a month followed by 6 placebo capsules for a month or 6 placebo capsules daily for a month followed by 6 fish oil capsules daily for a month. Each fish oil capsule contained 335 mg of salmon oil and 165 mg of commercial soy lecithin and provided 152 mg of omega-3 fatty acids. The placebo capsules contained 500 mg of pharmaceutical-grade liquid paraffin.
The researchers found that the CF patients who took fish oil showed a marked increase in their phospholipid levels of eicosapentaenoic acid [EPA] (increase of 327%) and docosahexaenoic acid [DHA] (increase of 215%). The levels of EPA and DHA returned to baseline 2 weeks after discontinuing supplementation. The researchers also noted that patients with low initial levels of EPA showed the greatest increase in EPA levels after supplementation. They conclude that oral supplementation with fish oil and lecithin is effective in increasing the levels of omega-3 fatty acids especially EPA and DHA in cystic fibrosis patients.
Source: Christophe, Armand, et al. Increase of long chain omega-3 fatty acids in the major serum lipid classes of patients with cystic fibrosis. Ann Nutr Metab, Vol. 36, 1992, pp. 304-12
Taking too much fish oil may increase triglyceride levels which can be harmful. Some studies have also shown that although Cfers don’t absorb as much essential fatty acids as non-Cfers, that high tyriglycerides may still occur.
A DGReview of :“Abnormal lipid concentrations in cystic fibrosis”
American Journal of Clinical Nutrition, 06/11/2002
By Mark Pownall
High levels of triglycerides in the blood are common in cystic fibrosis, questioning the traditional belief that lipid levels were not of concern in this group of patients.
The clinical significance of the findings may become more important as modern treatments result in patients with cystic fibrosis living longer, the researchers behind the study say.
The researchers, from the University of Minnesota in the United States, measured the fasting lipid profiles in 192 patients with cystic fibrosis. The patients also had an oral glucose tolerance test.
The CF patients of all ages had higher triacylglycerol and lower total cholesterol concentrations than the means of the US population. Thirty three of the patients (16 percent) had hypertriglyceridaemia, while eight had elevated cholesterol. levels.
Most of the patients had only hypertriglyceridaemia; only three had both high triglycerides and high cholesterol in their plasma samples.
There was no obvious correlation to other biochemical measurements. Lipid levels were not linked to body mass index, weight, glucose tolerance, the area under the curve or glucose or insulin, nor glycated hemoglobin levels.
There was also no link established with cystic fibrosis genotype, use of systemic steroids, blood pressure, liver enzymes, CV-reactive protein or pulmonary functio
In the face of all these negative findings, the researchers suggest that the hypertriglyceridaemia seen in cystic fibrosis patients may be related to a chronic low-grade inflammation or to a dietary macronutrient imbalance with an excess absorption of simple carbohydrate compared to fat.
The researchers say it is uncertain whether the lipid abnormalities are related to a risk of cardiovascular disease in the CF population.
Am J Clin Nutr 2002; 75: 1005-1011. “Abnormal lipid concentrations in cystic fibrosis”
So what are triglycerides?
Source: American Heart
Triglycerides are the chemical form in which most fat exists in food as well as in the body. They’re also present in blood plasma and, in association with cholesterol, form the plasma lipids.
Triglycerides in plasma are derived from fats eaten in foods or made in the body from other energy sources like carbohydrates. Calories ingested in a meal and not used immediately by tissues are converted to triglycerides and transported to fat cells to be stored. Hormones regulate the release of triglycerides from fat tissue so they meet the body’s needs for energy between meals.
How is an excess of triglycerides harmful?
Excess triglycerides in plasma is called hypertriglyceridemia. It’s linked to the occurrence of coronary artery disease in some people. Elevated triglycerides may be a consequence of other disease, such as untreated diabetes mellitus. Like cholesterol, increases in triglyceride levels can be detected by plasma measurements. These measurements should be made after an overnight food and alcohol fast.
So as parents what we want to know is – what does all this mean? Should we be giving our CF kids more fish oil? If so, how much more? How much is too much? And how much is enough? The above research suggests that effective doses of fish oil range from 4.5 to 5.3 g/d, providing 2.7 to 3.2 g/d of EPA and 1.8 to 2.1 g/d of DHA, but few other doses were evaluated.
The reality is that our doctors don’t know how much fish oil we should be giving our kids but understandably, will err on the side of caution. The question for me as a parent is, how harmful are larger doses of fish oil if I choose to follow the research and up the dosage? Should I be testing my child for high triglyceride levels? Is the dose he is currently on even high enough?
My son is 2 years old and currently on 4 x Metagenics EPHA / DHA capsules daily which deliver 500mg of triglycerides daily [165 mg EPA and 110 mg DHA] per capsule. If I can find anyone to give me advice on this I’ll update the site and let you know.>
Additional info on therapeutic dosages:
Typical dosages of fish oil are 3 g to 9 g daily, but this is not the upper limit. In one study, participants ingested 60 g daily. The most important omega-3 fatty acids found in fish oil are called eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In order to match the dosage used in several major studies, you should take enough fish oil to supply about 2 g to 3 g of EPA (2,000 mg to 3,500 mg) and about 1.0 g to 2.5 g of DHA daily (1,000 mg to 2,500 mg). Far higher doses have been used in some studies; conversely, one study found blood-pressure lowering effects with a very low daily dosage of DHA—0.7 g.238
DHA and EPA are not identical and might not have identical effects. Some evidence hints that DHA may be more effective than EPA for thinning the blood 176 and reducing blood pressure.105 The reverse may be true for reducing triglyceride levels, but study results are conflicting.160-165, 235
Some manufacturers add vitamin E to fish oil capsules to keep the oil from becoming rancid. Another method is to remove all the oxygen from the capsule. If possible, purchase fish oil products certified as free of significant levels of mercury, toxic organochlorines, and PCBs (see Safety Issues). Flaxseed oil also contains omega-3 fatty acids, although of a different kind. It has been suggested as a less smelly substitute for fish oil. However, it is far from clear whether flaxseed oil is therapeutically equivalent to fish oil.1,200. Studies to date suggest it is not.
The USA National Cholesterol Education Program guidelines for triglycerides are:
Common wisdom says that probotics are a useful supplement for anyone who takes regular antibiotics as they help support intestinal function and gut repair. There is a significant amount of research however to suggest that probiotic supplements are especially important for CFers. In particular, LGG [the lactobacillus GG strain]. Whilst we know that probiotics affect intestinal inflammation research suggests that a relationship exists between intestinal and pulmonary inflammation.
So what are Probiotics?
Our bodies are full of bacteria. Some bacteria make us sick, some help keep us well. Probiotics are foods or nutrition supplements that contain the good bacteria. Most of these organisms are ones that are already present in our bodies, but not always in sufficient quantity to be of the most benefit.
How Can Probiotics Help People with Cystic Fibrosis?
Several studies have been done about the benefits of probiotics. Two recent Italian studies have shown that the probiotic organism, Lactobacillus rhamnosus GG (LGG), can benefit cystic fibrosis patients in a couple of ways.
In the first study, the researchers just looked at the benefits to the intestines. They found that cystic fibrosis patients who take LGG may have a reduction in the intestinal inflammation that often causes them pain
A few years later, the same researchers decided to take it one step further and see how LGG affects the lungs of CF patients. They found that cystic fibrosis patients who took LGG regularly had less bouts with respiratory infections than those that didn’t take LGG.
Where Can I Find LGG?
Lactobacillus rhamnosus GG is available over the counter at many health food stores and pharmacies in capsule form. It is also available in some brands of yogurt. There are many products, including most yogurts with active cultures, that contain Lactobacillus acidophilus. While Lactobacillus acidophilus is a beneficial probiotic, it is not the same as LGG. Read the label carefully to be sure you’re a getting a product that contains LGG.
Sources: Bruzzese, E., Raia, V., Gaudiello, G., Polito, G., Buccigrossi, V., & Formicola, V. (2004). Intestinal inflammation is a frequent feature of cystic fibrosis and is reduced by probiotic administration. Aliment Pharmacol Ther. 20, 813-819
Bruzzese, E., Raia, V., Spagnuolo, M.I., Volpicelli, M., De Marco, G., Maiuri, L. (2007). Effect of Lactobacillus GG supplementation on pulmonary exacerbations in patients with cystic fibrosis: A pilot study. Clinical Nutrition. 26, 322-328.
Another study: Effect of Lactobacillus GG supplementation on pulmonary exacerbations in patients with cystic fibrosis: A pilot study
A prospective, randomized, placebo-controlled, cross-over study was performed. Nineteen children received LGG for 6 months and then shifted to oral rehydration solution (ORS) for 6 months. In parallel nineteen received ORS and then shifted to LGG. Main outcome parameters were: incidence of pulmonary exacerbations and of hospital admissions, forced expiratory volume (FEV1), and modifications of body weight.
Patients treated with LGG showed a reduction of pulmonary exacerbations (Median 1 vs. 2 , range 4 vs. 4, median difference 1, CI 95% 0.5–1.5; p=0.0035) and of hospital admissions (Median 0 vs. 1, range 3 vs. 2, median difference 1, CI95% 1.0–1.5; p=0.001) compared to patients treated with ORS. LGG resulted in a greater increase in FEV1 (3.6%±5.2 vs. 0.9%±5; p=0.02) and body weight (1.5kg±1.8 vs. 0.7kg±1.8; p=0.02).
LGG reduces pulmonary exacerbations and hospital admissions in patients with CF. These suggest that probiotics may delay respiratory impairment and that a relationship exists between intestinal and pulmonary inflammation.
Source: Clinical Nutrition Journal
The take-away >
Eating yoghurt, even healthy looking yoghurt like Valia may not give you a viable dose of probiotic. It’s certainly good for you but it may help to have an added boost. Experts suggest we need to be giving our kids a viable dose of a strong probiotic to support the gut. According to our clinical dietitian at the hospital, the Metagenics brand [ a natural offshoot of a pharma co.] is one of the stronger more viable “active” doses. And don’t bother with Yakult, experts says that a lot of sugar and the strain of probiotic it offers is not the most effective for their gut health.
Metagenics makes an LGG supplement if you’re interested.