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Home - In Focus August 2010 - Why Vitamin D Is Not Enough - 3 Articles

   In Focus August 2010 - Why Vitamin D Is Not Enough - 3 Articles
NutriCology In Focus Newsletter

Why Vitamin D is Not Enough

A Trio of Articles by Stephen Levine, PhD

A Bold New Approach to Supplementation

Though vitamin D deserves to be nominated nutrient of the decade for its amazing properties, the current recommendations and approach to this pro-hormone may be seriously misguided and at times even harmful.

This may be one of the most controversial positions we have ever taken in this timely and important edition of the Focus newsletter, and it’s certainly one of our most intensively researched; we’ve spent months interviewing experts and comparing many hundreds of peer-reviewed studies.  Our subject is vitamin D—the nutrient du jour, that mystic molecule that recently has graced the cover of the British Medical Journal and the pages of the New York Times, as well as grabbed the attention of most medical professionals and the entire American public.

But this is not just another vitamin D article. We’re offering you a bold and distinctly different perspective, with surprising findings that may radically shift the way you look at this astounding nutrient. In a nutshell: though vitamin D deserves to be nominated nutrient of the decade for its amazing properties, the current recommendations and approach to this pro-hormone may be seriously misguided and at times even harmful.  The current approach to vitamin D too often dismisses extremely important fat soluble co-factors, ignores receptor “cross talk” that is crucial for optimal health, and misses the potential for the development of serious deficiencies and toxicities if the hugely important variations in lifestyle, genetics and diet are not taken into account.

Vitamin D may be one of the most important nutrients in our nutritional armamentarium—and currently, one of the most misunderstood. If not given safely with the correct ratios of other fat soluble nutrients, vitamin D is a tool that turns into a weapon, one that can inadvertently harm. As a tool, vitamin D can help us fight infections and slash the risk of multiple sclerosis, diabetes, heart disease, cancer (colon, breast, skin and prostate), osteoporosis, dental caries, lupus and rheumatoid arthritis, and depression.1-14 There over 47,000 peer review studies on vitamin D, stretching all the way back to 1922, with the most recent entries on its powerful role in lupus, fractures and breast cancer.15-18 And yet, despite vitamin D’s promise, scientists still don’t know what optimal levels may truly be.19-21

We are, as a society, in the midst of what might be called a vitamin D renaissance—Quest Diagnostics, for instance, reports that orders for vitamin D tests surged more than 50% in 2009, as compared to 2008;22 innumerable peer-review journals as well as newspapers and magazines have covered what may be a nearly pandemic vitamin D deficiency in our society; and in 2008 consumers bought $235 million worth of vitamin D supplements, compared to $40 million in 2001.22

Vitamin D is light transformed. As I write this, on a gloomy afternoon, the lovely phrase of nutritionist and vitamin D specialist Krispin Sullivan, interviewed in this issue, keeps singing in my mind: ”There is a band of light, a very narrow band known as ultraviolet-B, upon which all life depends. That band of light—and its capture and storage in our bodies as vitamin D—is one of the great stories of our time.”23

This newsletter is about the vitamin D story, but we offer what we believe is a more complete story—the story of vitamin D and its irreducible helpers, which evolution wove together in an inseparable braid long ago. This newsletter is also about vitamin A, new findings on carotenes, and new research on vitamin K.

The research is stunningly clear: Vitamin D is part of an ancient complex molecular script. In fact, A, D, K and E work together, and the newest research shows that these lipid-based molecules are all powerful antioxidant nutrients which are intricately bound through shared receptors. They balance and enhance each other, and as a group, profoundly influence genes, immunity, inflammation and the healthy balance of lipids in our body.24

Overview:
Safely Supplement Vitamins D and A
– Key Concepts of this SPECIAL ISSUE –

•   Modest, regular doses of vitamin D can slowly and safely bring us to optimal levels—even in northern latitudes. However, regular monitoring with blood tests is crucial, due to genetic variation.25-28
•   Higher doses of vitamin D being recommended today have never been proven safe, especially longterm, and toxicity can show up overnight when fat stores become saturated and excess vitamin D spills into the blood; this can take many months to reverse.23, 29-32
•   High dose vitamin D may increase fracture risk in elderly women. Women age 70 years or older who received a single annual high dose of vitamin D had a higher rate of falls and fractures compared to women who received placebo, according to a study in the May 2010 issue of JAMA.33
•   Vitamin A deficiency is more common than we realize, because vitamin A-rich foods are rarely eaten and vitamin A toxicity has been overblown, to our profound immunological detriment.34, 43
•   Vitamin A is necessary for optimal mucosal immunity—and is a key nutrient in balancing the newly discovered pro-inflammatory cytokine, IL-17.35-44
•   Carotenes are not an adequate or safe substitute for vitamin A in supplements, even though they’ve long been recommended as a substitute. New research shows they are not efficiently converted to vitamin A in as many as 50% of individuals, and they can create cleavage products that form free radicals, interrupt vitamin A’s protective function, and thereby potentially raise the risk of cancer.45-47
•   Most important, vitamins D and A are an ancient and inseparable team that evolution has honed through time. They must be supplemented together in order to not create a “functional” deficiency of either one. Excess D will create a “relative” deficiency of A, even when dietary levels are adequate. And vice versa.24, 48-49
•   A good marriage is complementary—and the good marriage of vitamin A and vitamin D allows these two nutrients to balance, enhance, and contain each other, through an ancient (steroid) receptor called RXR. The all-important result, which cannot be achieved with either nutrient alone, is a beautifully functioning immune system that does not veer into autoimmune disease, or have trouble handling pathogens. And as we know, a healthy immune system is tightly linked to a healthy nervous system.
•   Vitamin D is the only molecule that we create ourselves from light and turn into a hormone (OH25D). An astounding feat when you think about it. Similarly, vitamin A, obtained through the diet, is the other dietary lipid-based nutrient that we turn into a hormone (retinoic acid).
•   Vitamin K brings up the rear, like a good third teamplayer, and enhances vitamin D’s impact on bone, and protects against kidney damage from excess D. The top vitamin K expert in this country, Sarah Booth, PhD of Tufts University, speculates that K may also work through the ancient RXR receptor, just like D and A. But that has not been studied yet.50
•   Finally, vitamin E seems to play a role as well, working together with vitamins A and D.
•   Fat-soluble vitamins are likely to be best absorbed when accompanied by a fatty meal, or in a fish oil base. What we take these vitamins with is as important as the vitamins themselves.23
•   Thus, safe and balanced doses of A, D, K and E in an oil base, is likeliest to lead to optimal health.

The Marriage of Vitamin D and
Vitamin A: A Match Made on Earth

By Stephen Levine, PhD

With the best of intentions, we have spurred a widespread deficiency in both vitamin A and vitamin D, a necessary team for optimal health and immune function. How has this twin deficiency contributed to the many immune disorders we see today?

Fact: Vitamin D reaches deep and far. Since 1979, we have identified over fifty different target tissues in the body that carry vitamin D receptors, from the bone to the kidneys, liver and intestines. Vitamin D helps regulate growth, reproduction, immunity, cardiovascular function, mood, and the neuroendocrine system. At least 200 genes are primary targets of its active, hormone form, and it indirectly regulates even more genes.23, 51-53

Fact: There is a vitamin D deficiency pandemic—50% of Americans may be lacking optimal amounts, which have been set at about 80 nmol/L (or 32 ng/ml)—what vitamin D expert Robert Heaney calls the “canonical” number, based on optimal intestinal calcium absorption. (Calcium is only one marker of vitamin D’s many functions, and according to Krispin Sullivan, CN, has been overemphasized as a solitary marker of utility and toxicity. Nonetheless, it is universally used). Vitamin D levels have dropped from an average of 30 ng/ml between 1988-1994 to 24 ng/ml between 2001-2004.23, 54-55

Fact: There is also a widespread vitamin A deficiency, since 50% of individuals may not be able to effectively convert carotenes to vitamin A, and the richest dietary sources of vitamin A (full fat milk, butter, eggs and liver) are often avoided by many individuals worried about weight or cholesterol.34, 46 As an important aside, there is also a vitamin K deficiency—not severe enough to impair clotting, for which tiny amounts are required, but a subtle deficiency that impacts vitamin D’s functions.56-58 Rich amounts of vitamin K are present in butter from grassfed cows. But cows today are fed mostly grain, and not pasture-fed.

Fact: We’re seriously sun-deprived. As noted in a 2007 study from the University of Wisconsin, “lack of sun exposure is widely accepted as the primary cause of epidemic low vitamin D status worldwide.”59-61 Even in sun-drenched climes, most of us work indoors by day and cover our skin with clothing when outside, liberally applying sunscreen to lower our risk of UV-linked damage and skin cancer. We’ve created the virtual equivalent of a cave—and cut off nature’s fine-honed mechanism for crafting a much-needed nutrient from light.62

Fact: Though Vitamin D does increase immune function and stimulate antimicrobial peptides, Vitamin A is essential for the immune function of the very mucosal tissues that are the greater part of our immune system (the gut lining). If you are deficient in Vitamin A you will not be able to migrate secretory IgA efficiently in order to wash away microbes.34, 63-64 As Michael Ash, D.O, N.D., writes in his piece on Vitamin A in this issue, “Tolerance in immunity defines health. An intolerant immune system will lead to an unhealthy person and the gut is where many people lose tolerance. Vitamin A is a missing piece of the puzzle of mucosal immunology.”

Fact: The scientific literature on both vitamins A and D can be bewilderingly inconsistent. Studies present a confusing picture on the role of sunlight, optimal levels of vitamin D and how to treat deficiency. We know that those with diabetes or kidney disease, dark skin, and infrequent sun exposure are at risk for vitamin D deficiency.25, 65-68 We know anecdotally, for instance, that the huge Somali population in Minneapolis suffers from severe vitamin D deficiency, having fled from the hot equator to a northern latitude.69 We have studies showing that higher levels of Vitamin A increase fracture risk—and studies that do not show the same risk.70-75 We have a study of young women living in Maine who were given 800 IU of vitamin D along with calcium in the winter months, and 80% reached a healthy vitamin D level over time.76 This study is unusual, because the women’s response was so good, and we do not know what other factors contributed, such as hormone status, youth, lifestyle, or diet.77

Fact: Sunlight exposure may not always be enough. Half of healthy individuals in eternally sunny Honolulu, Hawaii, who got a self-reported whopping average of 28.9 hours of golden rays a week, had low vitamin D status.78 Is there such genetic variability in the ability to convert sun to Vitamin D, that an astounding half of us simply need to supplement no matter what? Possibly. Some of us come from equatorial Africa, others from northern Scandinavia, where our ancestors adapted to plentiful or scant sunlight accordingly.

Fact: Nobody agrees on the optimal levels for supplementation of vitamin D or vitamin A.79 The Institute of Medicine’s Food and Nutrition Board is expected to soon raise the recommended dietary intake of 400 IU of vitamin D daily for the first time since 1997.80 According to vitamin D expert Robert P. Heaney, PhD, a daily oral intake of 2200 IU of vitamin D may be necessary to achieve optimal levels of vitamin D.54 His recommendation is echoed by Heike Bischoff-Ferrari, Ph.D., whose review of vitamin D studies concludes that 1,000 IU a day will bring 50% of the population to optimal levels.81-83 And yet, a study of healthy young women in Maine from September 2005 through February 2006—during the “vitamin D winter” where high latitude and lack of UV light mean we can’t manufacture the vitamin at all—found that supplementing with 800 IU of vitamin D and calcium brought 80% to optimal levels.76 800? 1000? 2200? What’s the right dose?

Meanwhile, virtually all supplements include carotenoids as pro-vitamin A, out of fear of toxicity for retinol itself. A close look at the research shows that fear to be questionable.47, 84-86

Rather than a pharmacological model (one nutrient isolated from others), we need a nutritional model that takes into account the diet and lifestyle with which we originally evolved, and the way our receptors respond to tightly linked nutrients.

And finally, a hypothesis: Rather than a pharmacological model (one nutrient isolated from others), we need a nutritional model that takes into account the diet and lifestyle with which we originally evolved, and the way our receptors respond to these nutrients. Studies can be inconsistent if they isolate a single factor, without taking into account the tight synergy among nutrients. For instance, research shows a positive impact on bone mineral density when both vitamin D and calcium are supplemented together—and none with vitamin D alone.87-91 One could wrongly conclude that vitamin D did not impact bone.

We now turn to the robust and largely unknown scientific literature showing how closely intertwined Vitamin D is with Vitamin A. If we understand how these two pro-hormones—as well as the two other fat soluble vitamins, K and E—aid each other, then a clear picture emerges of the healthiest, safest route to supplementation and optimal levels of these nutrients.

Crosstalk: A Key Concept For Correct Supplementation

Crosstalk. It might sound like two married couples bickering at each other without listening. But in fact it’s a fundamental mechanism hardwired into our biology, by which molecules dock at the same receptor and initiate a cascade of responses in the body. Crosstalk between vitamin A and vitamin D is writ into our biology, and if we look at studies on these two fat soluble nutrients with crosstalk in mind, we begin to understand how synergy has been misinterpreted as interference.

Receptors for vitamin A and vitamin D are found in every cell.92 They were even found in human sperm in 2006.93 Even more important, vitamins A and D share an ancient receptor in the nucleus of the cell known as retinoid X receptor (RXR).  RXR regulates lipid balance and it also crosstalks with other hugely important steroid receptors—such as thyroid, glucocorticoid, estrogen, progesterone, and testosterone. Though vitamin A binds to its own retinoic acid receptor (RAR) and vitamin D binds to its own vitamin D receptor (VDR), they then bind to RXR. A point that cannot be overemphasized: Because they share a receptor, if we supplement either vitamin D or vitamin A in an unbalanced fashion, we create a functional deficiency of the one not supplemented. In other words, even if our levels at baseline are adequate, adding just one to the exclusion of the other may create the equivalent of a deficiency.

The crosstalk between vitamins A and D has a profound impact on our health.

Key crosstalk effects include:

Liver reserves: Animal research shows that high levels of vitamin D lower vitamin A reserves in the liver.94-96

Cancer: Retinoic acid can help leukemia cells turn non-cancerous, and this effect is enhanced by the hormone form of vitamin D (calcitriol). And a synthetic vitamin D derivative along with a retinoid inhibits prostate cancer cells in vitro.97-103

The Heart: Low blood levels of vitamin D, vitamin A and carotenoids are all correlated with greater risk of heart disease.104-108

Bone: This is a key area of confusion and contention. Does Vitamin A increase risk of fracture? A 2009 study from the American Journal of Clinical Nutrition, reviewing 75,747 women from the Women’s Health Initiative, found no association between vitamin A intake and the risk of fracture in postmenopausal women. However, a modest increase was found with high vitamin A intake and low vitamin D.72 Our hypothesis: Given the fact that Vitamin D was already low in some individuals, and that high vitamin A will create a further “functional” deficiency, this makes sense. That may be why the highest rate of osteoporosis is found in northern Europe, where sunlight (vitamin D) is limited and vitamin A intake is high (through oily fish).109

Other recent research suggests balance is key. A study of 3,113 postmenopausal women living at higher latitudes in England found that vitamin A from cod liver oil supplements (which also contain vitamin D) did not impair bone health. Yet high vitamin A from food led to increased resorption of bone. The conclusion? “Retinol from supplements and food have different effects,” write the researchers, “which may in part be due to whether the source of retinol also provides vitamin D.”110

This argues for a balance of both nutrients, not a fear of either one. In fact, osteoblasts (which build bone) and osteoclasts (which break down bone) have receptors for both vitamins. Strong bone requires constant remodeling, and thus vitamin D and vitamin A must be in balance to optimize this process.111-113

Crosstalk is a fundamental mechanism hardwired into our biology, by which molecules dock at the same receptor and initiate a cascade of responses in the body. Crosstalk between vitamin A and vitamin D is writ into our biology, and if we look at studies on these two fat soluble nutrients with crosstalk in mind, we begin to understand how synergy between the two has been misinterpreted as interference.

Diabetes: In adults as well as children, vitamin A and vitamin D have been found to be deficient in type 1 diabetes.114 Fish oil supplements, which contain both vitamins, have been correlated with lower rates of Type 1 diabetes. In fact, the January 2009 issue of Diabetes asks if “a combination of vitamins A and D, in safe pharmacologically formulated doses…might be of benefit in the treatment of those at increased risk for type 1 diabetes.”115

The Immune System: Vitamin D helps dampen autoimmune responses and decrease pro-inflammatory T cell cytokines. Similarly, vitamin A increases regulatory T-cells that help dampen hypersensitivity reactions.1-4, 12, 13, 35-44, 116-121

The Brain: Here’s an amazing study that is probably just the tip of the iceberg, showing how both vitamin A and vitamin D can impact neurotransmitters in the developing brain—for life. Newborn male rats were treated with a single dose of 3 mg vitamin A or .05 mg of vitamin D, and three months later five brain regions were studied for tissue levels of dopamine, serotonin and other metabolites. The single dose of vitamins A and D functioned as a kind of hormonal imprinting in specific brain regions, and significantly altered levels of these molecules. The researchers conclude: “The profound and lifelong effect of neonatal hormonal imprinting on neurotransmitter production of the adult brain seems to be well established…the imprinting effect of vitamin A and vitamin D must be taken into consideration.”122

What can we conclude from all this? Both vitamin A and vitamin D are far more than vitamins, with profound effects on every tissue in the body, and they dance together. Through the RXR receptor, they are linked to our most potent steroid hormones. They are involved in regulation of everything from bone to the brain, the kidney to the immune system, the heart to the pancreas.49, 123-124 Adequate levels are crucial to health, and many of us are not getting enough of either, given our modern lifestyles and diet. With that in mind, we now proceed to the recommendations and insights of key experts on Vitamin A and Vitamin D.

Back to top

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In Focus on NutriCology®
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