DNC News

Denver, Sunshine and Tuberculosis

Jacob Schor, ND

September 9, 2006

 

Here in Denver we live with many reminders that not so long ago tuberculosis was a terrible disease that afflicted many lives. Denver 's rapid growth in the late 1800's was as much due to tuberculosis as to the gold rush. Some came seeking gold; many more came seeking sunshine and hoped for survival.

 

In years past sunshine was known to kill the tuberculosis causing organism. The only treatment available for tuberculosis was fresh food, fresh air, the colder the better, and sunshine. Especially sunshine. People came to Colorado for the sunshine and fresh air. Denver was famous for its sanatoriums. Lutheran hospital, Craig, National Jewish, the Jewish Workers Relief Society and its descendent, the AMC Cancer Research Center , all grew out of these early tuberculosis sanatoriums.

 

In the Park Hill neighborhood where I live, most of our homes date from that era and still exhibit reminders of those days. Houses were built with sleeping porches and sun porches, often the two were combined. Elevated as far from the ground as architecture allowed these were unheated screened in porches. Some were even built with slanting floors, so bedridden people with congested lungs filling with fluid could better breath.

Sleeping Porch

Hugh McLean residence at 7070 E. 11th Avenue in the Montclair Neighborhood of Denver, Colorado; features covered porches.

 

 

Sunbathing was an integral part treating tuberculosis. Hospitals were built with sunbathing facilities; patient beds were wheeled directly out onto verandahs, balconies, or decks so patients could bath in the sun light. Sunning wasn't just a summer pastime, it was year round with patients taking sun even in the middle of winter, bundled in blankets with only their face exposed.

Men sunbath in specially designed shelters at Lutheran Hospital, circa 1924

 

 

Ultraviolet light can certainly kill the Mycobacterium tuberculosis, the bacteria that causes this disease, and frequent sun exposure may have lessened the communicability of the disease. Aside from, this modern physicians have thought that sun exposure ineffective in treating tuberculosis. Sunbathing is now considered to be one of those curiously entertaining medical treatments that may have once been popular but which medicine has outgrown.

 

Perhaps we have been too fast to judge.

 

Exposure to sunlight stimulates the production of a hormone called calcitriol in the body; this hormone is usually referred to as vitamin D. Vitamin D is necessary for the body to absorb calcium from the digestive tract. Inadequate sunlight and vitamin D deficiency leads to a calcium deficiency and in childhood a disease of ‘soft bones' known as Rickets'.

 

Recent research has linked vitamin D deficiency with a new list of health conditions. These range from auto immune diseases such as rheumatoid arthritis, diabetes and multiple sclerosis, and cardiovascular diseases, including high blood pressure and heart attacks to many types of cancer.

 

 

It is in this light that sunbathing no longer seems so outmoded.

 

Sunbathing can increase the body's store of Vitamin D, potentially adding thousands of international units of vitamin D in a single session. Vitamin D status varies by ethnic group. The darker one's skin, the more sun exposure required to make vitamin D. In early 2005 it was reported that vitamin D status varied among European ethnic groups and correlated with their risk of getting tuberculosis. [i]

In the last two years, vitamin D's effect on immune function has begun to be explained and the mechanism for sunbathing's effect on tuberculosis is starting to make sense.

 

Tuberculosis patients lie in beds on the porch of a building at the Jewish consumptives

Relief Sanatorium, 1600 Pierce Street, Lakewood, CO.  This facility later became the American Medical Center and then the AMC Cancer Research Center.

Vitamin D acts as a potent immune modulator. It induces a Toll-Like Receptor (TLR) gene which in turn promotes production of human cathelicidin antimicrobial peptide (CAMP) by white blood cells. [ii] This CAMP stuff is part of the innate immune system and provides a rapid response used to repel assaults from numerous infectious organisms including bacteria, viruses, fungi, and parasites and tuberculosis. [iii] [iv] It is our first line of defense against infection.

 

A March 2006 study showed that by triggering the CAMP gene and stimulating production of these cathelicidin antibiotic like chemicals, vitamin D is useful for fighting tuberculosis. African Americans are much more susceptible to tuberculosis than white Americans. African Americans make less vitamin D than whites and as a result African Americans are slower at triggering CAMP proteins, producing less cathelicidin and leaving them more vulnerable to tuberculosis. [v]

 

 

A study published in January 2006 tells us that vitamin D supplementation is beneficial in treating tuberculosis. Sixty seven tuberculosis patient were randomized to receive vitamin D (0.25 mg/day) or placebo in a double blind method, during the 6th initial week of standard tuberculosis treatment. One hundred percent of the vitamin D group and only 76.7% of the placebo group had sputum conversion. [vi] Translated into simpler English, in this study, about a quarter of the patients in the control group were resistant to drug therapy, it didn't work. Giving vitamin D made the drug therapy work in 100% of the patients. Given that the World Health Organization estimates that there are 450,000 new multi-drug resistant cases of tuberculosis each year, this is significant, not just statistically but clinically.

 

This recent interest in traditional treatments for tuberculosis is not just academic. Tuberculosis is still with us. Mycobacterium tuberculosis still infects one-third of the world's population and kills nearly 2 million people a year. That's more deaths than from any other infectious bacteria.

Treating tuberculosis infection is difficult; current treatment requires four drugs in combination for 6 months or longer. That is when it works. The incidence of multi-drug resistant tuberculosis is growing. The newest drug designed to treat tuberculosis is thirty years old. The tuberculosis mycobacterium is a hard bug to kill. It surrounds itself with multiple layers of protective shells made of sugars and fats that make them almost impermeable and very resistant to attack. In the body, although macrophages quickly engulf the tuberculosis mycobacterium but are they are unable to destroy them and the infection can persist for years.

 

It looks reasonable to add vitamin D to any drug protocol used in treating tuberculosis.

Our current habit of shielding our bodies from the sun with clothing and sunscreens may in the future seem as unenlightened as many of the medical practices from the past that we now view with skepticism and consider to have been silly and ineffective.

 

 

Snowy view along a Modern Woodmen of America Sanatorium 'street', north of Colorado Springs, Colorado, shows a nurse and people in folding chairs outside their faceted, Gardiner tent huts, sunning themselve in the snow.

 

 

 

 

  References:

 

 

[i] J Infect. 2005 Jun;50(5):432-7. Click here to read  Links

Prevalence and associations of vitamin D deficiency in foreign-born persons with tuberculosis in London .

•  Ustianowski A ,

•  Shaffer R ,

•  Collin S ,

•  Wilkinson RJ ,

•  Davidson RN .

Department of Infection and Tropical Medicine, Lister Unit, Northwick Park Hospital , Harrow , Middlesex HA1 3UJ , UK . ustianowski@doctors.org.uk

OBJECTIVES: The incidence of tuberculosis (TB) is high amongst foreign-born persons resident in developed countries. Vitamin D is important in the host defence against TB in vitro and deficiency may be an acquired risk factor for this disease. We aimed to determine the incidence and associations of vitamin D deficiency in TB patients diagnosed at an infectious diseases unit in London , UK . METHODS: Case-note analysis of 210 unselected patients diagnosed with TB who had plasma vitamin D (25(OH)D3) levels routinely measured. Prevalence of 25(OH)D3 deficiency and its relationship to ethnic origin, religion, site of TB, sex, age, duration in the UK, month of 25(OH)D3 estimation and TB diagnosis were determined. RESULTS: Of 210 patients 76% were 25(OH)D3 deficient and 56% had undetectable levels. 70/82 Indian, 24/28 East African Asian, 29/34 Somali, 14/19 Pakistani and Afghani, 16/22 Sri Lankan and 2/6 other African patients were deficient (with 58, 17, 23, 9, 6 and 1 having undetectable levels, respectively). Only 0/6 white Europeans and 1/8 Chinese/South East Asians had low plasma 25(OH)D3 levels. Muslims, Hindus and Sikhs all had equivalent rates of deficiency though Hindus were more likely to have undetectable levels (odds ratio 1.87, 95% CI 1.27-2.76). There was no significant association between 25(OH)D3 level and site of TB or duration of residence in the UK . There was no apparent seasonal variation in either TB diagnosis or 25(OH)D3 level. CONCLUSIONS: 25(OH)D3 deficiency commonly associates with TB among all ethnic groups apart from white Europeans, and Chinese/South East Asians. Our data support a lack of sunlight exposure and potentially a vegetarian diet as contributors to this deficiency.

PMID: 15907552 [PubMed - indexed for MEDLINE]

 

[ii] FASEB J. 2005 Jul;19(9):1067-77. Click here to read  Links

Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3.

•  Gombart AF ,

•  Borregaard N ,

•  Koeffler HP .

Department of Medicine, Division of Hematology/Oncology, Cedars-Sinai Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, California 90048, USA. gombarta@csmc.edu

The innate immune system of mammals provides a rapid response to repel assaults from numerous infectious agents including bacteria, viruses, fungi, and parasites. A major component of this system is a diverse combination of cationic antimicrobial peptides that include the alpha- and beta-defensins and cathelicidins. In this study, we show that 1,25-dihydroxyvitamin D3 and three of its analogs induced expression of the human cathelicidin antimicrobial peptide (CAMP) gene. This induction was observed in acute myeloid leukemia (AML), immortalized keratinocyte, and colon cancer cell lines, as well as normal human bone marrow (BM) -derived macrophages and fresh BM cells from two normal individuals and one AML patient. The induction occurred via a consensus vitamin D response element (VDRE) in the CAMP promoter that was bound by the vitamin D receptor (VDR). Induction of CAMP in murine cells was not observed and expression of CAMP mRNA in murine VDR-deficient bone marrow was similar to wild-type levels. Comparison of mammalian genomes revealed evolutionary conservation of the VDRE in a short interspersed nuclear element or SINE in the CAMP promoter of primates that was absent in the mouse, rat, and canine genomes. Our findings reveal a novel activity of 1,25-dihydroxyvitamin D3 and the VDR in regulation of primate innate immunity.

PMID: 15985530 [PubMed - indexed for MEDLINE]

 

[iii] J Immunol. 2004 Sep 1;173(5):2909-12.Click here to read

 

Erratum in:

J Immunol. 2004 Nov 15;173(10):following 6489. Hanrahan, JH [corrected to Hanrahan, JW].

 

Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression.

 

* Wang TT,

* Nestel FP,

* Bourdeau V,

* Nagai Y,

* Wang Q,

* Liao J,

* Tavera-Mendoza L,

* Lin R,

* Hanrahan JW,

* Mader S,

* White JH.

 

Department of Physiology, McGill University , Montreal , Quebec , Canada .

 

The hormonal form of vitamin D(3), 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), is an immune system modulator and induces expression of the TLR coreceptor CD14. 1,25(OH)(2)D(3) signals through the vitamin D receptor, a ligand-stimulated transcription factor that recognizes specific DNA sequences called vitamin D response elements. In this study, we show that 1,25(OH)(2)D(3) is a direct regulator of antimicrobial innate immune responses. The promoters of the human cathelicidin antimicrobial peptide (camp) and defensin beta2 (defB2) genes contain consensus vitamin D response elements that mediate 1,25(OH)(2)D(3)-dependent gene expression. 1,25(OH)(2)D(3) induces antimicrobial peptide gene expression in isolated human keratinocytes, monocytes and neutrophils, and human cell lines, and 1,25(OH)(2)D(3) along with LPS synergistically induce camp expression in neutrophils. Moreover, 1,25(OH)(2)D(3) induces corresponding increases in antimicrobial proteins and secretion of antimicrobial activity against pathogens including Pseudomonas aeruginosa. 1,25(OH)(2)D(3) thus directly regulates antimicrobial peptide gene expression, revealing the potential of its analogues in treatment of opportunistic infections.

 

PMID: 15322146 [PubMed - indexed for MEDLINE]

 

[iv] FASEB J. 2005 Jul;19(9):1067-77.Click here to read

Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3.

 

* Gombart AF,

* Borregaard N,

* Koeffler HP.

 

Department of Medicine, Division of Hematology/Oncology, Cedars-Sinai Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, California 90048, USA. gombarta@csmc.edu

 

The innate immune system of mammals provides a rapid response to repel assaults from numerous infectious agents including bacteria, viruses, fungi, and parasites. A major component of this system is a diverse combination of cationic antimicrobial peptides that include the alpha- and beta-defensins and cathelicidins. In this study, we show that 1,25-dihydroxyvitamin D3 and three of its analogs induced expression of the human cathelicidin antimicrobial peptide (CAMP) gene. This induction was observed in acute myeloid leukemia (AML), immortalized keratinocyte, and colon cancer cell lines, as well as normal human bone marrow (BM) -derived macrophages and fresh BM cells from two normal individuals and one AML patient. The induction occurred via a consensus vitamin D response element (VDRE) in the CAMP promoter that was bound by the vitamin D receptor (VDR). Induction of CAMP in murine cells was not observed and expression of CAMP mRNA in murine VDR-deficient bone marrow was similar to wild-type levels. Comparison of mammalian genomes revealed evolutionary conservation of the VDRE in a short interspersed nuclear element or SINE in the CAMP promoter of primates that was absent in the mouse, rat, and canine genomes. Our findings reveal a novel activity of 1,25-dihydroxyvitamin D3 and the VDR in regulation of primate innate immunity.

 

PMID: 15985530 [PubMed - indexed for MEDLINE]

 

[v]

Science. 2006 Mar 24;311(5768):1770-3. Epub 2006 Feb 23.

 

 
Comment in:

•  Science. 2006 Jun 30;312(5782):1874-5; author reply 1874-5.


Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response.

Liu PT , Stenger S , Li H , Wenzel L , Tan BH , Krutzik SR , Ochoa MT , Schauber J , Wu K , Meinken C , Kamen DL , Wagner M , Bals R , Steinmeyer A , Zugel U , Gallo RL , Eisenberg D , Hewison M , Hollis BW , Adams JS , Bloom BR , Modlin RL .

Department of Microbiology, Immunology, and Molecular Genetics, University of California at Los Angeles , Los Angeles , CA 90095 , USA .

In innate immune responses, activation of Toll-like receptors (TLRs) triggers direct antimicrobial activity against intracellular bacteria, which in murine, but not human, monocytes and macrophages is mediated principally by nitric oxide. We report here that TLR activation of human macrophages up-regulated expression of the vitamin D receptor and the vitamin D-1-hydroxylase genes, leading to induction of the antimicrobial peptide cathelicidin and killing of intracellular Mycobacterium tuberculosis. We also observed that sera from African-American individuals, known to have increased susceptibility to tuberculosis, had low 25-hydroxyvitamin D and were inefficient in supporting cathelicidin messenger RNA induction. These data support a link between TLRs and vitamin D-mediated innate immunity and suggest that differences in ability of human populations to produce vitamin D may contribute to susceptibility to microbial infection.

PMID: 16497887 [PubMed - indexed for MEDLINE]

 

[vi] Acta Med Indones. 2006 Jan-Mar;38(1):3-5. Links

The effect of vitamin D as supplementary treatment in patients with moderately advanced pulmonary tuberculous lesion.

•  Nursyam EW ,

•  Amin Z ,

•  Rumende CM .

Departement of Internal Medicine, Faculty of Medicine, University of Indonesia-dr.Cipto Mangunkusumo Hospital, Jakarta .

AIM: to compare the vitamin D group of pulmonary tuberculosis patients with a placebo group in terms of clinical improvement, nutritional status, sputum conversion, and radiological improvement. METHODS: sixty seven tuberculosis patient visiting the Pulmonary Clinic, of Cipto Mangunkusumo Hospital , Jakarta , from January 1st to August 31st, 2001 were included in this study. The subjects were randomised to receive vitamin D (0.25 mg/day) or placebo in a double blind method, during the 6th initial week of Tb treatment. The rate of sputum conversion, complete blood counts, blood chemistry as well as radiologic examination were evaluated. RESULTS: there were more male patients than females (39:28), 78.7% were in the productive age group, 71.6% had low nutritional status, 62.4% with low education level, and 67.2% with low income. One hundred percent of the vitamin D group and only 76.7% of the placebo group had sputum conversion. This difference is statistically significant (p=0.002). CONCLUSION: the sputum conversion had no correlation with the hemoglobin level, blood clotting time, calcium level, lymphocyte count, age, sex, and nutritional status. There were more subjects with radiological improvement in the vitamin D group.

PMID: 16479024 [PubMed - indexed for MEDLINE]

 


 

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