In this article, the first of 3 parts focusing on vitamin D, I will be discussing a nutrient which is relevant regarding not only both calcium and magnesium nutrition and the maintenance of immunological integrity, but also the prevention and treatment of a wide spectrum of chronic diseases, including cancer and heart disease.
Until relatively recently, discussions of vitamin D focused primarily on the major role it plays in calcium metabolism and bone growth and mineralization. In this reference, it promotes absorption of calcium and phosphorus from the intestines, and the reabsorption of calcium in the kidneys.
Vitamin D promotes bone mineralization, but when it is deficient, bones can become thin, brittle, soft, or misshapen. Rickets in children and osteomalacia (soft bones) and osteoporosis in adults are associated with Vitamin D deficiency.
Rickets is a childhood disorder characterized by inhibited growth, and deformity, of the long bones. The role of diet in the development of rickets was established around 1920 when it was demonstrated that cod liver oil could prevent or alleviate this deficiency disease. In the 1930s in the U.S., the initiation of the practice of fortifying milk with vitamin D (400 IU per quart) led to a dramatic decline in the number of cases of rickets, which, prior to that, had been a major public health problem.
Osteomalacia is a bone-thinning disorder in adults characterized by bone fragility, muscle weakness and musculoskeletal pain. Osteoporosis (meaning porous bones) is a common degenerative condition characterized by reduced bone mineral density and increased bone fragility.
Maintenance of serum calcium levels within a narrow range is vital not only for bone growth and maintenance of bone density but also for normal functioning of the nervous system. When the parathyroid glands (located on either side of the thyroid gland) sense a drop below a certain threshold in serum calcium levels, they secrete parathyroid hormone (PTH). In turn, an elevation in PTH increases the activity of Vitamin D.
Heightened Vitamin D activity serves to normalize low serum calcium levels by increasing the intestinal absorption of dietary calcium and the reabsorption of calcium filtered by the kidneys and by mobilizing calcium from bone when dietary calcium reserves are too low to maintain normal serum calcium levels.
Importantly, magnesium not only helps the body to metabolize calcium, it converts dietary vitamin D to calcitriol (the active dihydroxy metabolite of vitamin D), helps to maintain the integrity of skeletal bone-crystal formation, and it is required for the binding of both calcium and fluorine to bone and tooth enamel. Lacking magnesium, both calcium and fluorine cannot be properly utilized by bones and teeth, thus, they are excreted from the body.
Clinical evidence demonstrates that magnesium deficiency, common among women with primary postmenopausal osteoporosis, contributes to poor responsiveness by the body to vitamin D. This inhibits vitamin D’s role in intestinal calcium absorption.
Vitamin D: Crucial For Much More Than Strong Bones
As the role of vitamin D in bone health is well known, I would not be devoting three consecutive articles to a discussion of this vital nutrient if it was essential solely to the maintenance of the skeletal system. In fact, inadequate vitamin D nutrition contributes to the development of virtually every major chronic disease; also, it is critical to resistance to acute infections, including the flu.
Vitamin D actually has a dual identity. Up until recently, only its vitamin identity has been highlighted. However, it is also what is referred to as a secosteroid (the prefix seco is a Latin word which means “to cut”). A secosteroid is a compound derived from a steroid in which there has been a cleavage of one or more of its ring structures. As a secosteroid, vitamin D’s metabolic product: calcitriol is involved in the regulation in a large number of genes, many of which are responsible for bodily repair and maintenance.
The scientific standard for assessing an individual’s vitamin D status is the serum concentration of 25-hydroxyvitamin D (referred to in biochemistry as 25(OH)D)–which is the metabolic precursor of the vitamin D hormone calcitriol. Deficient 25(OH)D levels are not only common but prevalent in both Europe and North America.
Calcitriol is involved with the operations of approximately 2,000 genes within the body, representing fully 10% of the human genome. Accordingly, vitamin D shortfall can have a devastating systemic impact. For instance, research has now demonstrated that vitamin D deficiency is a contributory factor to the development of many different types of cancer, autoimmune diseases, multiple sclerosis, cardiovascular disease, high blood pressure, stroke, obesity, diabetes (including Type 1 diabetes), migraine headache, macular degeneration, periodontal disease, asthma, tuberculosis, cystic fibrosis, colds and influenza, Inflammatory Bowel Disease, osteoarthritis, rheumatoid arthritis, osteoporosis, chronic pain, muscle weakness, birth defects, infertility, eczema, psoriasis, depression (including seasonal affective disorder), insomnia, autism, schizophrenia, cognitive impairment, including memory loss, senility and Alzheimer’s disease.
It has been observed that those suffering with Parkinson’s disease tend to have low blood levels of vitamin D. It is unclear as to whether low vitamin D levels play a role in the pathogenesis of Parkinson’s disease or if vitamin D shortfall is somehow a product of the disease. In either case, the importance of therapeutic sunbathing and vitamin D supplementation for those suffering from Parkinson’s disease is clearly indicated.
Vitamin D and Cancer
A growing body of research is substantiating the crucial nature of vitamin D regarding the prevention and treatment of cancer. In laboratory experiments, it has been demonstrated that vitamin D3 can inhibit the growth of breast cancer, leukemia, and malignant melanoma. Vitamin D is required for normal operation of the immune system, the regulation of cellular growth and the inhibition of angiogenesis (the development of new blood vessels). Cancer cells require new blood vessels in order to grow and metastasize.
It is thought that the vitamin D hormone calcitriol induces cancer cell death via its role within the cell nucleus that regulates cell growth, differentiation, apoptosis (a genetically determined process of cell self-destruction) and other cellular mechanisms central to the development of cancer. It is now known that not only the skin, but the colon, breast, prostate, a type of white blood cells called macrophages and other organs have the enzymatic machinery to produce vitamin D. Also, vitamin D receptors are present in many tissues, including malignant cells and so may contribute to the successful use of vitamin D in the treatment of some types of cancer.
Epidemiological studies (i.e., studies that examine the causes, distribution, and control of disease in populations) show an inverse association between sun exposure, vitamin D intake and serum levels of 25-hydroxycholecalciferol and the risk of developing or surviving cancer. There is a direct correlation between the risk of developing cancer and the distance one lives from the equator. The equatorial region is of course bathed in sunlight throughout the year. People who live in higher latitude regions have significantly higher cancer rates than those living closer to the equator. A recent Australian study reported a definitive correlation between latitude and the incidence of pancreatic cancer.
By correlating NASA-generated UVB data and regional maps of internal cancer death rates, Dr. William Grant, Ph.D., a leading vitamin D researcher, found that mortality levels in the northeastern United States were nearly double those in the southeast. He hypothesizes that this disparity is related to chronic vitamin D deficiency. Similarly, while the annual cancer rate in tropical countries averages 25 per 100,000, the incidence of cancer in Iceland is 90 per 100,000.
Grant has noted that the majority of cancer deaths in the United States are from those cancers that are either ignited, or exacerbated, by vitamin D shortfall. It has been estimated that simply increasing vitamin D levels in the general population could prevent 150,000 cases of cancer per year, in the U.S. alone.
Higher serum levels of the main circulating form of vitamin D: 25-hydroxyvitamin D are associated with substantially lower incidence rates of colon, breast, ovarian, renal, pancreatic, aggressive prostate and other cancers. Researchers have shown that daily supplementation with 1,000 IU (International Units) of vitamin D can reduce colon cancer risk by 50%, and breast and ovarian cancer risks by 30%. Similarly, the National Cancer Institute has found that vitamin D was beneficial in preventing colorectal cancer. A 2006 study found that taking as little as 400 IU of vitamin D per day cut the risk of pancreatic cancer by 43%. There is also evidence that high levels of calcitriol exert a beneficial effect upon outcomes in men with advanced prostate cancer.
It has been demonstrated that there is a direct correlation between low serum levels of vitamin D and breast cancer progression and metastasis to the bones. Increased supplementation with vitamin D may also reduce the risk of breast cancer in premenopausal women.
Vitamin D and Heart Disease
Cardiovascular disease is a worldwide epidemic in terms of mortality. It is especially serious in Western countries with heart disease, surpassing even cancer in mortality. Despite our understanding of how to prevent the development of cardiovascular disease, it still remains the leading cause of death in the United States and a major cause of disability.
About every 25 seconds, an American will have a coronary event, and about one person per minute will die from that event. Although mortality from cancer is on the rise, the annual number of deaths due to heart disease surpasses the total for all cancers combined.
Vitamin D appears to play a similarly vital role in preventing or reversing heart disease. Deficient 25(OH)D concentrations are associated with increased mortality (including sudden cardiac death) in those with increased cardiovascular disease risk or preexisting cardiovascular disease. Thus, it is unsurprising that vitamin D deficiency has been associated with high blood pressure and other cardiovascular risk factors, including elevated triglycerides, peripheral artery disease (PAD) and impaired insulin metabolism. A study conducted in England found that cholesterol levels in gardeners decreased during the summer (the season of maximal sunlight exposure). In the temperate zone, but not in tropical latitudes, the incidence of heart attacks peak in winter and decline in summer.
One study found that, compared to individuals with normal serum levels of vitamin D, those with low serum vitamin D levels had a 62% higher risk of a cardiovascular disease-related event. Both vitamin D and calcium play crucial roles in the contraction (required to pump the blood), and other aspects, of cardiac muscle performance including left ventricular function. The left ventricle is the chamber of the heart that pumps the blood out to the body. Low levels of vitamin D are very common in heart failure patients.
Atherosclerosis (progressive narrowing and hardening of the arteries over time) is a disease process in which cholesterol, calcium, and abnormal cells accumulate in the walls of the coronary arteries, forming plaque-like deposits that can lead to blockage of the arteries. Calcium deposits are a prominent feature of many atherosclerotic plaques in coronary arteries.
The coronary arteries (so-called because they encircle the heart like a crown) arise from the aorta adjacent to the heart and are responsible for supplying the heart muscle with oxygenated blood. Coronary artery disease begins when hard plaques build up within a coronary artery. These plaques can cause a clot to form that can obstruct the flow of blood to the heart muscle, thus setting the stage for a heart attack. Lower 25-hydroxyvitamin D concentrations are associated with increased risk for calcification of the coronary arteries.
The incidence of congestive heart failure is growing rapidly, especially among elderly people. It is a condition that results from weakness of the heart muscle, which, in turn, causes the heart to lose its pumping ability. Consequently, fluid backs up in the lungs and may also accumulate in the legs.
The majority of congestive heart failure patients have insufficient serum levels of vitamin D levels. Given that skin-synthesis is the most important vitamin D source for humans, it is notable that congestive heart failure patients typically have relatively low outdoor activities. There is an accumulating body of evidence that vitamin D deficiency plays a major role in the causation and step-by-step development of congestive heart failure. Vitamin D exerts both direct impact on heart cells and indirect effect on the risk factors of congestive heart failure. In this regard, it is required for normal heart muscle contractile function, natriuretic hormone secretion (hormones involved with the regulation of fluid volume), remodeling (reorganization or renovation) of the extracellular matrix (fluid matrix which surrounds each cell) and regulation of inflammation cytokines (non-antibody proteins released by specific types of cells as part of the body’s immune response).
The connection between low serum vitamin D and increased cardiovascular risk is not restricted to adults. It has been shown that among adolescents in the United States, deficient vitamin D status is strongly associated with high blood pressure, elevated blood sugar, and metabolic syndrome. Importantly, persistent vitamin D shortfall increases these risk factors in adolescents, regardless of whether they are obese or of normal weight.
Conclusion
Clearly, the maintenance of optimal vitamin D nutrition is absolutely crucial for protecting against both cancer and heart disease. However, as discussed above, vitamin D deficiency is commonly a factor in the development of a wide array of other diseases as well. In the next issue of Nature’s Therapies, I will discuss vitamin D’s value in the prevention and treatment of flu infection and the link between vitamin D deficiency and autism.
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