Take a Deep Breath

Breathing comes so naturally that much of the time we don’t even notice that we’re doing it – unless we get out of breath after heavy exertion. That pressured feeling soon passes, and breathing becomes invisible again. But for some that feeling never goes, and the constant struggle for air experienced by sufferers of chronic obstructive lung disease (COLD), who tend to be progressively more out of breath until they die, is harrowing. Inhaling oxygen-enriched air helps up to a point, but the main medical focus on COLD has always been on prevention; and as the main causes of COLD are tobacco and occupational exposure to toxins such as asbestos, this has fed into smoking cessation campaigns, safer working practices, and compensation claims which have provided surprisingly large sums of money for the legal profession (Guardian ’11). There has been very little that could be done to manage or improve COPD.

Until now. 

A randomised and placebo-controlled clinical trial was recently carried out at the Queen Mary University of London, looking at the effect of vitamin D supplementation on the severity and duration of COPD symptoms over a 12-month period (Martineau et al ’16). This was a large trial involving 240 patients, who were given either placebo or oral vitamin D3 at doses of 3 mg given once every 2 months throughout the year. 

In the sub-group of patients who were D-deficient at the start of the trial, vitamin D significantly lowered the number and severity of flare-ups; the 40% reduction in the number of flare-ups was described by the trial authors as ‘dramatic’.  D supplementation had no effects in the group who entered the trial with normal levels of the vitamin.

So how was vitamin D achieving these results?

D is essential for immune function, and plays a role in increasing resistance to infection, but the incidence of upper respiratory tract infections did not change in this group. Vitamin D has many other functions in the body however, one of which is a role in reducing inflammation.

Low vitamin D status has been linked to many inflammatory diseases, and as vitamin D has potent anti-inflammatory effects it consequently has been considered for adjunctive therapy for numerous chronic diseases including asthma (Searing et al ’10), arthritis (Plum et al ’10), prostate cancer (Krishnan et al ‘10) and Type 1 diabetes (Mao et al ’14) and chronic inflammatory pain (Hirani ‘12).

A good deal of research has investigated how D exerts its anti-inflammatory effects, and it appears to do so via many different mechanisms. D is known, for example, to enhance the function of regulatory T suppressor cells, which dampen the activity of pro-inflammatory immune cells (ie Chambers & Hawrylowicz ’11). A recent paper revealed another part of this complex story. A Chinese research team (Zhang et al ’12) found that D also directly reduces the formation of pro-inflammatory cytokines by various white blood cells that are involved in driving chronic inflammation, including macrophages and monocytes.

As over a billion people are thought to be D-depleted, and as D is both cheap and safe, there is a strong case for giving D supplements to anyone with an inflammatory condition such as COPD – but the case for better nutrition does not stop there.

Retinoids such as vitamin A modulate and enhance the effects of vitamin D (ie Carlberg ’96), and they have direct anti-inflammatory effects of their own (ie Akdeniz et al ’05). In a clinical investigation carried out at the Helmholz Centre in Munich, vitamin A aerosols produced very significant improvements in lung function and quality of life in a patient with COPD (Frankenberg et al ’09). This was only a single patient, and I do not normally report on such experiments, but the very detailed biochemistry provided important insights into what was happening. The blood work showed that the vitamin A had a sufficiently strong anti-inflammatory effect to reduce the activity of a group of tissue-destructive enzymes called proteases. This not only stopped the lung damage from progressing, it also seemed to allow for the repair / regeneration of a significant amount of lung tissue.

Regeneration of lung tissue is not classically thought to occur but I have long suspected that a degree of repair might be possible, given the right circumstances. The alveoli, where gas exchange takes place, are fragile and dynamic organelles, and are probably being constantly re-modelled  – as indeed all other tissues are, from bone to liver, muscle, catilege and skin.  In a patient whose biochemistry is pro-inflammatory, due to factors such as smoking and/or poor nutrition, the net loss of alveoli will always outstrip any regenerative capacity. But if that person’s biochemistry can be amended to provide an anti-inflammatory and generally supportive environment, then healing should be able to predominate, as it can do after pneumonia. While extensive scarring and other major structural losses are probably irreparable, there seems no intrinsic reason why individual alveoli cannot be repaired or even regenerated.

Another consideration for any self-medicator with COPD is to add polyphenols to the mix. Not only do they enhance the effects of vitamin D (Dampf-Stone et al ’14), they also have strong anti-inflammatory effects of their own which they exert, inter alia, by blocking the effects of the proteases referred to above. Add high dose fish oil, and the insidious process of chronic inflammation that drives COPD would be, in my estimation and limited experience, suppressed thoroughly enough to provide the best possible chance of lung tissue regeneration.

Bibliography: 

Akdeniz N, Calka O, Ozbek H, Metin A. Anti-inflammatory effects of tretinoin (all-trans-retinoic acid) 0.1% and adapalene 0.1% in rats. Clin Exp Dermatol. 2005 Sep;30(5):570-2.

Carlberg C. The vitamin D(3) receptor in the context of the nuclear receptor superfamily : The central role of the retinoid X receptor. Endocrine. 1996 Apr;4(2):91-105

Chambers ES, Hawrylowicz CM. The impact of vitamin D on regulatory T cells. Curr Allergy Asthma Rep. 2011 Feb;11(1):29-36. 

Dampf-Stone A, Batie S, Sabir M, Jacobs ET, Lee JH, Whitfield GK, Haussler MR, Jurutka PW. Resveratrol Potentiates Vitamin D and Nuclear Receptor Signaling. J Cell Biochem. 2014 Dec 23. doi: 10.1002/jcb.25070. [Epub ahead of print]

Guardian.co.uk. Neil Rose. Miners’ compensation: why did some solicitors take too big a slice of the pie? Tuesday 8 March 2011 13.06 GMT

Hirani V. Vitamin D status and pain: analysis from the Health Survey for England among English adults aged 65 years and over. Br J Nutr 2012;107(07),1080-1084.

Krishnan AV, Feldman D. Molecular pathways mediating the anti-inflammatory effects of calcitriol: implications for prostate cancer chemoprevention and treatment. Endocr Relat Cancer. 2010;17:R19–38.

Mao L, Ji F, Liu Y, Zhang W, Ma X. Calcitriol plays a protective role in diabetic nephropathy through anti-inflammatory effects. Int J Clin Exp Med. 2014 Dec 15;7(12):5437-44

Martineau AR et al (20 authors).
Vitamin D3 supplementation in patients with chronic obstructive pulmonary disease (ViDiCO): a multicentre, double-blind, randomised controlled trial. Lancet Respiratory Medicine 2015;3(2),120-130

Plum LA, DeLuca HF. Vitamin D, disease and therapeutic opportunities. Nat Rev Drug Discov. 2010;9:941–955.

Searing DA, Zhang Y, Murphy JR, Hauk PJ, Goleva E, Leung DY. Decreased serum vitamin D levels in children with asthma are associated with increased corticosteroid use. J Allergy Clin Immunol. 2010;125:995–1000.

Zhang Y, Leung DY, Richers BN, Liu Y, Remigio LK, Riches DW, Goleva E. Vitamin D inhibits monocyte/macrophage proinflammatory cytokine production by targeting MAPK phosphatase-1. J Immunol. 2012 March 1;188(5):2127-35