Vitamin D The New Vitamin Revolution

There is a vitamin revolution brewing, and it is important to the health of young and old alike as researchers respond to what has been called the “vitamin D deficiency epidemic.” More than a dozen scientists at leading universities both in the United States and abroad have minced no words about it: many of us need more vitamin D. (See “Cod liver oil, vitamin A toxicity, frequent respiratory infections, and the vitamin D deficiency epidemic.”)¹ The issue of deficiency may be especially true of children, yet it is also applicable to adults. Quite surprisingly as far as vitamin D is concerned, the suggested intakes in recent decades have fallen rather wide of the mark. Not only are the recommendations of 400 IU/day as an adequate intake (100 percent of U.S. Daily Value) and 2,000 IU/day as an upper limit too low, but also recommendations may have been more realistic 70 years ago. As detailed below, in a tale of two vitamins, A and D, scientists initially bet on the wrong one.

Vitamin D Versus Viral Respiratory Infections
All the way back in 1926, it was theorized that a disorder in vitamin metabolism linked to a lack of sun exposure is responsible for the rise in infections experienced during the winter months.² Experiments in the 1930s provided considerable support for this hypothesis. Using a cod liver oil much higher in vitamin D content than is typical today, one large trial involving 185 adults for four months discovered that supplementation reduced the rate of infections with colds by 50 percent.³ Another study tracking 1,561 adults found the rate of respiratory infections fell by 30 percent.⁴ Recent work comparing 410 teenage athletes who received vitamin-D producing radiation against 446 athletes who did not over a period of three years demonstrated the same range of benefits as was seen with cod liver oil supplementation in the 1930s: 50 percent fewer respiratory infections and 300 percent fewer lost days due to absences.⁵

How does vitamin D provide protection against infections? This has been the subject of considerable work and the answer seems to be vitamin D produced in the skin in response to sunlight provides the body with the vitamin in its hormonal form known as 1,25(OH)2D, actually a type of steroid hormone. Indeed, the skin has the capacity to synthesize the biologically active vitamin D metabolite 1,25(OH)(2)D3.⁶ The active form of vitamin D serves both to reduce the excessive production of inflammatory factors and, yet, to increase the power of other immune elements, such as the “oxidative burst” of the macrophages, the immune system’s first line of defense. The effects of the vitamin on the immune system are particularly striking in an area that touches directly on defenses against colds and respiratory infections/flu. The lining of the respiratory tract is full of neutrophils, monocytes and natural killer cells, all of which contain anti-microbial peptides that are empowered by vitamin D.⁷

These benefits are known for sun exposure. Great news for the summer months, but can the use of vitamin D supplements help to provide the same protection? Luckily, the answer is “yes.” In a randomized placebo-controlled intervention trial lasting three years, it was discovered African American women receiving vitamin D exhibited only one third the likelihood of reporting cold or flu symptoms as did controls. The amount of vitamin D needed to abolish completely the tendency towards more colds and flu in the winter months was only 800 IU/day. Increasing the intake of supplemental vitamin D to 2,000 IU/day almost entirely eliminated reports of upper respiratory tract infections.⁸

Vitamin D and Vitamin A: A Conflicted Relationship
Recent studies using cod liver oil have not produced as robust a response in preventing infections as those found in the 1930s. Why not? The answer appears to be tied to the tendency over the last few decades to overrate the importance of vitamin A and to underrate the importance of vitamin D. Cod liver oil-based studies in recent years have used supplements typically providing 3,500 to 5,000 IU vitamin A as preformed retinol and only in the neighborhood of 700 IU vitamin D. The problem in this is vitamin A and vitamin D competes against one another because they make use of common cofactors. Vitamin A acts as an antagonist to vitamin D and its active metabolite.

That there might be an untoward interaction between vitamin A and vitamin D has been suspected for quite some time. Research at several laboratories has confirmed this suspicion. In an animal study, it was found there is an in vivo antagonism of vitamin D action on intestine and bone by retinyl acetate.⁹ Exactly how vitamin A antagonizes vitamin D is not entirely clear, but the fact is being ever more soundly established.¹⁰ Moreover, in human beings the amount of vitamin A needed to interfere with aspects of vitamin D metabolism is not high. For instance, one serving of liver as a vitamin A source interferes with vitamin D’s effects on the intestinal response to calcium.¹¹ Many Americans are marginal or outright deficient in vitamin D. In such cases, the amount of vitamin A supplied by multi-vitamins and other sources is sufficient to tip matters over the edge into significant manifestations, such as reduced bone health.¹² Although vitamin A deficiency is a serious issue in parts of the developing world, predominantly due to a lack of adequate fat in diet impeding absorption of this fat-soluble vitamin, once vitamin A requirements are met, there is a significant negative interaction with vitamin D.

Cardiovascular Health and the Sunshine Vitamin
The role of vitamin D in cardiovascular health is one of the currently “hot” topics in research circles, and for good reason. Vitamin D levels have been linked to a number of aspects of heart and circulatory health. Take blood pressure, for instance. It generally is assumed that blood pressure, primarily systolic blood pressure (the upper figure), increases naturally with age. This is the reason the elevation over time is named “age-associated increase in systolic blood pressure.” Interestingly, maintaining “optimal” vitamin D status reduces or attenuates the elevation in blood pressure that is expected with age.¹³ Another circulatory condition, lower-extremity peripheral arterial disease, similarly is related to vitamin D status. Nearly one third of the higher prevalence of this condition in adult blacks compared to whites is explainable by vitamin D levels being lower in blacks.¹⁴

Another way of thinking about vitamin D and cardiovascular health is to consider the lively discussions ongoing in research circles regarding the relationship of statins and vitamin D. Cardiovascular disease has a large inflammatory component and some scientists have argued that statins act, in large part, by serving as vitamin D analogs. Moreover, another aspect of cardiovascular disease concerns vascular calcification and statins recently have begun to be touted for bone health as well as reducing calcification of the arteries.

As is true of many substances, vitamin D is biphasic in some of its actions. Too much is a bad thing, but too little can lead to some of the same results as too much. Above it was mentioned that the vitamin plays a role in reducing inflammation. This is significant to heart health because arterial inflammation is an important step in the process leading to calcification. Hence, it is of note that in an animal model, low levels of the vitamin D hormone calcitriol are associated with massive vascular and soft tissue calcifications.¹⁵ That’s right: low levels of vitamin D-related compounds may lead to vascular and soft tissue calcification. Findings are interesting enough that researchers have begun to discuss vitamin D in the prevention and treatment of coronary heart disease.¹⁶

So what about statins and vitamin D? Much evidence available for over a decade suggests that statin drugs are cardio-protective via anti-inflammatory effects on the artery wall and not through any impact on cholesterol levels. Hence it is of note that treatment with statins, at least over the short and medium term, increases serum vitamin D by an unknown mechanism.¹⁷ At the same time, vitamin D deficiency, which is quite common in those with cardiovascular problems, appears to play a role in the myalgia associated with statin use.¹⁸

In other words, at least some of the benefits attributed to statin drugs, whether cardiovascular or bone-related, appear to be linked to improved vitamin D status. Likewise, at least one of the side effects of statin usage is linked to vitamin D deficiency.

Guarding Cognitive Health
Poor mood often is associated with advancing years. Recent data suggests that poor vitamin D status may be common in the elderly and low levels of vitamin D are associated with poor mood. There are a number of trials that have suggested a role for supplementary vitamin D in the treatment of depression.¹⁹ The impact of vitamin D status, however, appears to go far beyond merely improving mood. A large trial involving 1,766 adults over the age of 65 identified vitamin D levels as related to cognitive function and dementia. The relationship is strong enough that the researchers suggested supplementation with vitamin D as a possible way to reduce the risk of developing dementia.²⁰

How Much is Enough?
As usual, the devil is in the details. How much vitamin D is enough? Quite obviously, there likely is a range and not any one figure involved. People are different, get different amounts of sun exposure, have different diets, different stresses, and so forth. One recent study argues that the amount of vitamin D intake needed to attain the desired serum 25-hydroxyvitamin D concentration may run between 3,800 and 5,000 IU per day, amounts in excess of the currently officially endorsed upper limit of intake.²¹ These amounts are based on the researchers’ estimate of the intake of vitamin D3 needed to raise serum 25(OH)D to equal to or greater than 75 nmol/L and is in line with long-time recommendations of many experts of 3,000 to 5,000 IU/day.²² Other researchers using a different model of sun exposure and intake from food while restricting themselves to the requirements of Caucasians only still determined that a reasonable level of intake to prevent seasonal fluctuations may be as much as approximately 1,600 IU/day.²³ Again, this is a far cry from the presently recommended 400 IU/day. Moreover, some individuals have low vitamin D status even with abundant sun exposure.²⁴ All of this suggests the recommendation for vitamin D intake may soon be revised strongly upwards and that the currently suggested upper limit of intake of 2,000 IU/day may, instead, become closer to baseline.

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