Vit D and Flu

Something that can explain why flu epidemics also occur both in warm and cold climates is this: During a flu epidemic, wherever it may be, the atmosphere blocks ultraviolet B (UVB) radiation from the Sun. In the temperate zones above latitude 35 degrees North and South, the sun is at a low enough angle in the winter that the ozone layer in the atmosphere absorbs and blocks the short-wavelength (280–315 nanometers) UVB rays. In the tropics during the wet season, thick rain clouds block UVB rays.

Skin contains a cholesterol derivative, 7-dehydrocholesterol. UVB radiation on skin breaks open one of the carbon rings in this molecule to form vitamin D. The activated form of vitamin D (1,25-dihydroxyvitamin D) attaches to receptors on genes that control their expression, which turn protein production on or off. Vitamin D regulates the expression of more than 1,000 genes throughout the body. They include ones in macrophages, cells in the immune system that, among other things, attack and destroy viruses. Vitamin D switches on genes in macrophages that make antimicrobial peptides, antibiotics the body produces. Like antibiotics, these peptides attack and destroy bacteria; but unlike antibiotics, they also attack and destroy viruses.

Vitamin D also expresses genes that stop macrophages from overreacting to an infection and releasing too many inflammatory agents – cytokines – that can damage infected tissue. Vitamin D, for example, down regulates genes that produce interleukin-2 and interferon gamma, two cytokines that prime macrophages and cytotoxic T cells to attack the body’s tissues. In the 1918–19 Spanish flu pandemic that killed 500,000 Americans, young healthy adults would wake up in the morning feeling well, start drowning in their own inflammation as the day wore on, and be dead by midnight, as happened to my 22-year-old grandmother and my wife’s 24-year-old grandmother. Autopsies showed complete destruction of the epithelial cells lining the respiratory tract resulting, researchers now know, from a macrophage-induced severe inflammatory reaction to the virus. In a terribly misguided way, these victims’ own immune system attacked and killed them, not the virus, something in future pandemics vitamin D, in appropriate doses, can prevent.

A creditable hypothesis that explains the seasonal nature of flu is that influenza is a vitamin D deficiency disease. Cannell and colleagues offer this hypothesis in “Epidemic Influenza and Vitamin D” (Epidemiol Infect 2006;134:1129–40). They quote Hippocrates (circa 400 B.C.), who said, “Whoever wishes to investigate medicine properly should proceed thus: in the first place to consider the seasons of the year.” Vitamin D levels in the blood fall to their lowest point during flu seasons. Unable to be protected by the body’s own antibiotics (antimicrobial peptides) that this gene-expresser engineers, a person with a low vitamin D blood level is more vulnerable to contracting colds, influenza, and other respiratory infections (e.g., respiratory syncytial virus).

Studies show that children with rickets, a vitamin D-deficient skeletal disorder, suffer from frequent respiratory infections; and children exposed to sunlight are less likely to get a cold. Given vitamin D’s wide-ranging effects on gene expression, other studies, for example, show that people diagnosed with cancer in the summer have an improved survival compared with those diagnosed in the winter (Int J Cancer 2006;119:1530–36).

A growing body of evidence indicates that rickets in children and osteomalacia in adults (both a softening of bones due to defective bone mineralization) are just the tip of a vitamin D-deficiency iceberg. Tuberculosis and various autoimmune diseases, such as multiple sclerosis, lupus, and type I diabetes have a causal association with low vitamin D blood levels. Vitamin D deficiency plays a causal role in hypertension, coronary artery disease, congestive heart failure, peripheral vascular disease, and stroke. It is also a risk factor for metabolic syndrome and type II diabetes, chronic fatigue, seasonal affective disorder, depression, cataracts, infertility, and osteoporosis. At the bottom of the vitamin D iceberg lies cancer. There is good evidence that vitamin D deficiency is a causal factor in some 15 different common cancers. (NEJM 2007;357:266–81.)

The increased number of deaths that occur in winter, largely from pneumonia and cardiovascular diseases, are much more likely due to vitamin D deficiency than to an increased prevalence of serologically-positive influenza virus (which also results from vitamin D deficiency).

Experts reckon that an optimum blood level of vitamin D (25-hydroxyvitamin D) is 50–99 ng/ml. (Children need a blood level >8 ng/ml to prevent rickets. It takes a concentration >20 to maintain parathyroid hormone levels in a normal range. A level >34 is needed for peak intestinal calcium absorption. And in elderly people neuromuscular performance steadily improves as vitamin D blood levels rise to 50 ng/ml.) The government’s recommended daily allowance (RDA) for vitamin D is 400 IU (international units) a day, an amount sufficient to prevent rickets and osteomalacia but not vitamin D’s other gene-regulating benefits. To achieve all of vitamin D’s benefits one has to take an amount ten times the government’s RDA – 4,000 to 5,000 IU a day.

A light-skinned person will synthesize 20,000 IU of vitamin D in 20 minutes sunbathing on a tropical beach, at which point vitamin D synthesis shuts down for the day (it takes a dark-skinned person 6 to 10 times longer to make this amount). Human breast milk does not contain vitamin D, since, from an evolutionary standpoint, our African ancestors’ infants, reared near the equator, could readily synthesize this gene regulator from sunlight in their skin. Food contains very little vitamin D. (The highest concentrations are in wild salmon, mackerel, sardines, and cod liver oil.) Federal regulations now require that some foods, like milk, be fortified with vitamin D. But one would have to drink 200 glasses of milk to obtain the amount of vitamin D a light-skinned person can make in 20 minutes sunbathing.

The majority of Americans are vitamin D deficient, with a 25-hydroxy D blood level <20 ng/ml, or insufficient, with a level of 20–<30 ng/ml. Cheap vitamin D supplements (D3, not D2) provide the only way most of us can maintain a year-round vitamin D blood levels greater than 50 ng/ml. That requires taking 4–5,000 IU of vitamin D a day (50,000 IU every ten days or 150,000 IU a month).

Taking vitamin D in these doses is safe, far safer than a flu shot with all the bad chemicals it contains. Concerns about vitamin D toxicity are overblown. One can take a 10,000 IU vitamin D supplement on a daily basis without any adverse effects. In healthy persons, long-term consumption of more than 40,000 IU a day is necessary to cause an elevation in the blood calcium level (hypercalcemia), the first manifestation of vitamin D toxicity (Am J Clin Nutr 2006;84:694–97). Check your vitamin D (25-hydroxy D) blood level. People with granulomatous diseases like sarcoidosis should also check their blood level of 1,25-dihydroxyvitamin D, the active form.

Can a shot (or tablets) of vitamin D prevent influenza better than a flu shot? There is good reason to believe that it can.

Doctors in India and Canada give people a once-yearly injection of 600,000 IU of vitamin D (MJA 2005;183:10–12). That would be better, and safer, than having a flu shot. Daily, weekly, or monthly vitamin D tablets work just as well. For more on this subject see my article “Vitamin D in a New Light” and visit Dr. Cannell’s Vitamin D Council website.

Investigators have completed one double-blind, randomized, placebo-controlled trial that shows vitamin D prevents colds and influenza significantly better (P <0.002) than a placebo pill (Epidemiol Infection 2007;135:1095–6). A large multi-center randomized trial conducted over multiple flu seasons comparing vitamin D to a flu shot can show conclusively which is better, and safer. But given the financial stakes underpinning flu shots, and unpatentable vitamin D, who will fund it?

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