Other Diseases

Cardiovascular Disease

Hypertension is one of the most common risk factors for cardiovascular disease (CVD).  Inverse associations between 25(OH)D and blood pressure (both systolic and diastolic) have been observed ( Scragg et al, 2007 ).  This inverse relationship may explain some of the well-known regional and ethnic differences in hypertension ( Scragg et al, 1995 ;  Rostand, 1997 ).  Mortality rates from heart disease have been found to be 30% lower in the summer (when UVB exposure is high) compared with the winter ( Douglas et al , 1991). Exposure to UVB radiation (the main source of vitamin D) has been shown to dramatically increase 25(OH)D concentrations and decrease blood pressure in mildly hypertensive adults ( Krause et al. 1998 ). 

Cancer

Various epidemiologic studies have reported that individuals living at more northern latitudes are at increased risk of colon, prostate and breast cancer.  An ecological study in the US ( Grant, 2002 ) demonstrated that cancer mortality rates are inversely correlated with solar UVB exposure for 13 types of cancer (bladder, breast, colon, oesophagus, kidney, non-Hodgkin lymphoma, ovary, prostate, rectum, stomach, uterus, lung and pancreas).  A prospective study revealed that if serum 25(OH)D concentrations were below 50nmol/l, then there was a 2-fold increased risk of developing colon cancer ( Garland et al, 1989 ).  A sub analysis of the Nurses’ Health Study found a significant trend between 25(OH)D concentrations and distal and rectum cancer in women above the age of 60-years ( Feskanich et al, 2004 ).  However, in the largest prospective randomised study to date (Womens Health Initiative), 10µg of vitamin D3 plus calcium (1g) per day for 7 years did not modify colon cancer incidence ( Wactawski-Wende et al, 2006 ).  A possible role of vitamin D in preventing or slowing common cancers is that activated 1,25(OH)₂D is a strong inhibitor of cancer cell proliferation.  In animal studies several 1,25(OH)₂D analogs have been able to significantly reduce tumour growth; however, research is limited.  Research linking low vitamin D status with increased cancer incidence remains inconclusive and warrants further study.

Inflammatory-related diseases

Rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation of the joints.  Data from the Iowa Women's Health Study (IWHS) showed that a greater dietary intake of vitamin D was inversely associated with RA risk ( Merlino et al, 2004 ).  In addition, a negative correlation has been observed between serum 25(OH)D concentrations and RA activity ( Cutolo et al, 2006 ).  Vitamin D has a role in immunomodulation and may reduce RA activity by immune suppression ( DeLuca & Cantorna, 2001 ). 

Multiple sclerosis

Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system (CNS).  MS affects approximately 250,000 in the USA, 85,000 people in the United Kingdom, and 6,000 in Ireland ( http://www.ms-society.ie ).  MS causes gradual destruction of myelin (nerve insulator), causing various symptoms depending upon which signals are interrupted. 

There is a strong genetic component underlying the prevalence of MS but there are also a number of possible environmental factors, including vitamin D status.  MS is a disease that is essentially unknown at the equator and the prevalence of MS increases in populations further away from the equator ( Hayes, 2000 ).  This is thought to be due to decreased UVB exposure and therefore poor 25(OH)D concentrations ( Hayes et al. 1997 ). A large epidemiological study showed that women with the highest vitamin D intakes (>10µg/d) had a 40% reduction in the risk of developing MS ( Munger et al , 2004).  Experimental autoimmune encephalomyelitis (EAE) is a mouse model for human MS which presents the opportunity for determining the impact of various agents (e.g. vitamin D) that might be useful in the therapy or prevention of MS.  Studies have shown that 1,25(OH)2 D can suppress the induction of EAE but calcium levels must also be high ( Cantorna et al. 1996 ;  Cantorna et al. 1999 ).  There are several mechanisms believed to be responsible for the beneficial effects of vitamin D in MS including:

• Inhibition of inflammatory T-helper cells

• Inhibition of production of inflammatory cytokines

• An enhanced production of anti-inflammatory cytokines

• An anti-proliferative action in lymphocytes by the expression of VDR ( Hayes et al. 1997 ). 

Crohn's disease

Crohn’s disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) which have a combined incidence rate of 15-25/100,000 in Western Europe.  Crohn’s disease can affect any area of the digestive tract, from the mouth to the anus, but it most commonly affects the lower part of the small intestine, called the ileum.  As a result, patients have poor absorption of vitamins and general malaise.

Low vitamin D status is common in patients with CD ( Haderslev et al, 2003 ;  Jahnsen et al, 2002 ).  Osteopenia and osteoporosis are common in CD patients, arising from multifactorial mechanisms including nutritional inadequacies including calcium, vitamin D and vitamin K.  Osteopenia is seen in about 30% of CD patients, while 10-12% of patients have osteoporosis ( Bjarnason et al, 1997 ;  Szulc & Meunier, 2001 ).  Lower vitamin D status has been found in CD patients when compared to control subjects, despite similar intakes of vitamin D ( McCarthy et al,2005 ).  Both CD and ulcerative colitis (UC) patients have altered bone turnover relative to that in healthy controls ( Gilman et al, 2006 ).

Diabetes

Diabetes is a disease in which the body does not produce or properly use insulin. Insulin is a hormone that is needed to convert sugar, starches and other food into energy needed for daily life.  In type 1 diabetes (insulin dependent diabetes mellitus, IDDM), the destruction of the beta cells in the pancreas leads to insufficient insulin production. Patients are usually young, present acutely and often require emergency treatment for diabetic ketoacidosis (coma).  The pathogenesis of type 1 diabetes is thought to involve environmental triggers that may activate autoimmune mechanisms in genetically susceptible individuals. It accounts for approximately 10%-15% of all cases of diabetes in European populations ( Wass & Shalet, 2002 ). 

Type 2 diabetes (non-insulin dependent diabetes mellitus, NIDDM) is the most common form of diabetes. It occurs because the body produces too little insulin and is unable to properly use the insulin that is secreted.  It usually occurs in older adults although it is becoming more common among younger adults and even teenagers, partly due to lifestyle factors such as diet, lack of physical activity and obesity.  Type 2 diabetes accounts for approximately 85%-90% of all cases of diabetes in European countries ( Wass & Shalet, 2002 ).  In 2005, it was estimated that 5.4% adults and 4.7% adults over the age of 20 had diabetes (Type 1 and Type 2 combined) in Northern Ireland and the republic of Ireland, respectively ( The Irish Diabetes Prevalence Working Group, 2006 ).   

Seasonal variation in the prevalence of diabetes has been observed, with the largest proportion of IDDM cases diagnosed during autumn/winter and the lowest during the summer, suggesting a link with vitamin D status ( Cantorna, 2000 ).  Cod liver oil is a good source of vitamin D and a Norweigan study observed that daily consumption of cod liver oil during pregnancy could reduce the risk of diabetes in offspring ( Stene et al. 2000 ).  Intervention studies with vitamin D and 1, 25(OH)₂D have shown positive effects on blood glucose and serum insulin levels.  It has been shown that children treated with 50µg/d of vitamin D from 1 year of age had 80% reduced risk of developing type 1 diabetes mellitus by 80% throughout the next 20 years ( Hypponen et al. 2001 ).

Bone-related disorders

Rickets

Vitamin D deficiency was recognized as the cause of rickets early in the twentieth century.  Generally, 25(OH)D concentrations below 20-25nmol/l are associated with rickets.  Rickets is a disorder of mineralization of the bone matrix (osteoid) involving both the growth plate (epiphysis) and newly formed cortical and trabecular bone. Once thought to be eradicated, rickets has recently been reported in Northern latitudes, including Ireland and the UK.  Vitamin D deficiency in children can also prevent them reaching their genetically programmed height and peak bone mass. 

Osteomalacia

Vitamin D deficiency causes  secondary hyperparathyroidism , which can lead to osteomalacia and irreversible bone loss.  Osteomalacia is a softening of the bones caused by a defect in bone matrix mineralization and leads to increased fracture risk ( Lips, 2001 ).  It differs from rickets as it occurs once bone growth has been completed.

Osteoporosis

In Ireland, osteoporosis is diagnosed in 1 in 3 women and 1 in 5 men over the age of 50. Data from the International Osteoporosis Foundation (IOF) show that in 2000 there were 3.8 million osteoporotic related fractures in Europe.  Osteoporosis is a condition in which bones become porous and weak. As they lose strength, bones are more likely to fracture, particularly in the spine, hip, wrist, pelvis, and upper arm.

Although osteoporosis is a multifactorial disease, vitamin D deficiency is believed to be a major contributor.  Many patients with osteoporotic fractures have low serum 25(OH)D concentrations ( Boonen  et al. 1996 ;  Souberbielle  et al, 2006 ).  A clinical trial involving elderly people indicate a positive benefit of vitamin D supplementation (with calcium) in reducing fracture risk ( Dawson-Hughes  et al , 1997 ).