Health Solutions That Work

By Ralph Sanchez, L.Ac.,CNS,D.Hom.

There is a considerable body of research establishing the role of vitamin D in optimizing health. Besides its implicit role in calcium metabolism, bone health, and the prevention and treatment of osteopenia and osteoporosis, vitamin D deficiency is linked to several types of cancer, autoimmune diseases, infectious diseases, hypertension, stroke and cardiovascular diseases, type 1 diabetes, insulin resistance and metabolic syndrome, and neurological health. Now add a higher rate of mortality to the list. New evidence is now emerging that vitamin D deficiency could cut your life short.

Vitamin D Deficiency & Mortality

Several recent studies have shown a link between low serum vitamin D levels [25 (OH) D], and lower survival rates in the elderly. Just this month (11/2009), a study published in Nutrition Research revealed a link between Vitamin D deficiency and a “higher risk of mortality”. Vitamin D levels in 719 women, ages 70 to 79, and part of Women’s Health and Aging Studies I and II in Baltimore, Md., were analyzed over a 72-month period. The women with the lowest levels of 25 (OH) D (less than 15.3 ng/mL or 38.2 nmol/L), were at higher risk of death compared to women who with the highest levels of 25 (OH) D. (1)

Another large cohort study* of 3,258 male and female patients examined the the link between vitamin D deficiency, cardiovascular disease and higher rates of mortality, revealed that low vitamin D levels were independently associated with mortality from cardiovascular disease and all-cause mortality**. (2) The authors of the study reported that: “Low 25-hydroxyvitamin-D [25(OH)D], and 1,25-dihydroxyvitamin-D [1,25(OH)D] levels seem to be important mediators of mortality even when there is little or no indication of overt vascular disease.”

All Cause Mortality

While it is not established that vitamin D deficiency causes higher  mortality rates, the link between vitamin D deficiency, vitamin D insufficiency,  and higher mortality in many degenerative diseases is accumulating. Moreover, an analysis of mortality rates in 13,331 adults, 20 years and older, that were part of the Third National Health and Nutrition Examination Survey, revealed that apart from increased mortality rates in cardiovascular disease and cancer, vitamin D levels below 17.8 ng.dl (44.4 nmol/L), were found to be associated with all cause mortality  in the general population. (5)

There is considerable evidence that vitamin D is protective against the incidence of cancer, and that low 25 (OH) D levels are a significant risk factor for cancer mortality. Both observational studies *** in animals and humans support that vitamin D has a beneficial role in cancer survival and prevention. The mechanism of action is suggested to be due to its role in the regulation of cell growth and differentiation. The strongest association between vitamin D, it’s clinical application in the prevention and treatment of cancers, and the decreased risk of death, is in prostate, breast, ovarian, colon, and possibly Multiple Myeloma. (3,4)  Note that in the case of prostate, ovarian and other cancers, the downstream and active metabolite of 25 (OH)D, 1,25 (OH) D, as calcitriol, is the effective intervention. Calcitriol functions as a potent steroid hormone and imparts the health benefits attributed to Vitamin D. Besides a downstream metabolite of 25(OH)D, Calcitriol as a synthetic form of vitamin D, is also medical prescriptive drug. While calcitriol is a complimentary treatment option in certain types of cancer, vitamin D3 (cholacalciferol) is the supplemental form  that is used to optimize serum levels of 25(OH)D. Optimizing serum vitamin D levels (discussed below), may be one of the most important prevention strategies against the types of cancers noted above, and many other degenerative diseases associated with aging.

Apart from cardiovascular disease and cancer, low serum vitamin D levels were found related to increased mortality in most patients with chronic kidney disease before dialysis. (5) Another study demonstrated decreased mortality risk in patients receiving vitamin D supplementation. (6)

In summary, if you are living with cancer, cardiovascular or kidney disease, you are at risk for dying sooner if you have lower levels of vitamin D [25(OH)D], than your counterparts that have higher circulating 25(OH)D. However, you are not immune to the risk of an earlier trip to the grave if you are not afflicted by the aforementioned diseases. Anyone with suboptimal levels of circulating 25(OH)D, is at risk of becoming a statistic in mortality rates linked to vitamin D deficiency.

Vitamin D Deficiency

Many, if not most aging individuals, do not have optimal circulating vitamin D to support wellness, prevent many degenerative disease associated with aging, and as pointed out above, enough circulating vitamin D to reduce their risk for becoming a mortality statistic. Bear in mind that vitamin D deficiency, or insufficiency (defined below), is not restricted to older adults.

Young adults and children are commonly at risk for low levels of vitamin D [25(OH)D].  Individuals with darker skin pigmentation and those living in northern latitudes (above 30° N latitude) are particularly at risk.  Low levels of 25-hydroxy-vitamin D (25-OH D), the prime marker for evaluating vitamin D sufficiency, is estimated to be prevalent in as many as 50 to 60% of the aging population worldwide. (2)

The Dietary Recommended Intake (DRI)**** of vitamin D intake through supplementation, has long stood at 400 to 600 IUs/day for adults, and half that for children (200 IUs-see tables below). These recommended intakes were set to prevent severe deficiency of vitamin D, and the prevention of rickets and bone disease. However, vitamin D deficiency is now considered to be an epidemic. Rickets is not an uncommon condition here in the U.S and around the globe-even in the sunniest of climes. (7)

In 2008, the American Academy of Pediatrics (AAP) issued recommended intakes for vitamin D to exceed the 200 IUs Adequate Intakes of vitamin D set for children. Numerous clinical studies that preceded that advisory not only indicate that 200 IUs were inadequate to prevent rickets, but that at least 400 to 1,000 IUs were necessary for infants to “achieve a healthy 25(OH)D level of greater than 30 ng/ml” and correct vitamin D deficiency at birth. (7) Similar studies concluded that oral pharmacological doses of 2,000 to 4,000 for 3 to 6 months, or periodic single oral doses of 200,000 IUs were necessary to reverse rickets. (7)

As described above, there is significant and growing evidence that higher intakes are needed for the possible prevention, and treatment of many other chronic health disorders associated with aging. The medical community has only recently begun to embrace what an impressive body of research indicates. Higher recommended intakes of vitamin D, in the very young to a more mature individual, is important for the maintenance and optimization of health and vitality, and the prevention of a host of disease states.

Indeed, the more enlightened approach to vitamin D supplementation seeks to optimize serum vitamin D levels for the sake of enhancing health. What constitutes optimum, or sufficient vitamin D to promote wellness and possibly prevent health disorders and diseases, is now being distinguished from vitamin D deficiency that is well associated with rickets and osteomalacia (bone softening). Simply preventing overt deficiency may not be enough. In fact, a new standard for vitamin D sufficiency is now being shaped by a mountain of research that is gradually being integrated into more progressive and enlightened medical practice. So what constitutes “sufficiency”, and what is a frank vitamin D deficiency?

A scan of the research literature regarding vitamin D deficiency, reveals a generalized consensus regarding overt vitamin D deficiency (defined as serum 25-hydroxyvitamin D [(25(OH)D] under 8-10 ng/mL [or 20-25 nmol/L]) and a more suboptimal vitamin D levels, or vitamin D insufficiency (defined as serum 25-hydroxyvitamin D under 16-32ng/ml [or 40-80 nmol/L]). (2,8) Note the range of 25(OH)D that may be defined as insufficiency-16-32ng/ml (40-80 nmol/L). There is not any official standard for what can be considered a cut off level for vitamin D deficiency in context of optimal circulating vitamin D levels. The field of vitamin D research reveals both the more conservative, and the more liberal upper end of recommended serum vitamin D levels. Nevertheless, whether you are in the low end, a more severe deficiency vitamin D status, or you are closer to the cut off that indicates an “insufficiency”; it is in reality a consensus that speaks to a vitamin D deficiency spectrum. (9)

In my article: “Osteoporosis And Bone Health - Why The Optimal Intake Of Vitamin D and K Is More Important Than Calcium Supplementation Part 1 “, I made the case for optimizing serum vitamin D levels through much higher intakes of vitamin D3.  Therein I wrote: A study published in American Journal of Clinical Nutrition’s July 2006 issue recommended that “the most advantageous serum concentrations of 25-OHD (25-hydroxyvitamin D), the vitamin D marker that reflects biological activity, begins at 75 nmol/L (30 ng/mL), and “the best range being from 90 to 100 nmol/L (36–40 ng/mL)” (10). The study analyzed optimal vitamin D levels in relation to not only bone mass density*, but fracture rate, risk of falling, oral health, and colorectal cancer as well. The researchers also concluded that such levels could not be achieved with currently recommended daily intakes of 200 IU vitamin D for younger adults and 600 IU vitamin D for older adults (see tables below, and that a daily dose at least 1000 IU of Vitamin D3 is mandatory to bring 50% of the population up to optimal levels.

In the same article, I also pointed to a study of healthy adult men, it was determined that between 3,000 to 5,000 IUs of vitamin D3 intake during winter months was necessary to maintain blood levels achieved during the previous fall months. (11) In addition, the US-based Council for Responsible Nutrition (CRN) upon review of numerous clinical trials, recommended that the tolerable upper intake level (UL) for oral vitamin D3 should be increased five-fold from the current 2,000 IUs/day for adults, to 10,000 IUs/day. (12)

In a research paper overviewing the issue of vitamin A toxicity and the current vitamin D deficiency epidemic, Dr. John Hathcock of the Council for Responsible Nutrition, and 16 other well-known experts who have tirelessly advanced the need for revising current DRIs, and for higher intakes of vitamin D3 declared: “The 1997 FNB (Food and Nutrition Board ) recommendations offend the most basic principles of pharmacology and toxicology, leading us to conclude that the current official guidelines and limitations for vitamin D intakes are scientifically indefensible.” (see Table 1 and Table 2 below for the current government DRIs**** on vitamin D). (13)

Note, that there are only Allowable Intake (AI) and Tolerable Upper Intake Levels (UL) for vitamin D set forth by the Food and Nutrition Board (FNB). AIs are set in lieu of RDAs when evidence is insufficient to develop an RDA.

Table 1

Dietary Supplement Fact Sheet: Vitamin D

Daily Adequate Intake (AI) of Vitamin D

Table 2

Daily Adequate Intake (AI) of Vitamin D

Tolerable Upper Intake Level (UL) of Vitamin D

The most recent study (1/2010), examining the need for higher intakes of vitamin D3, evaluated winter and summer serum 25(OH)D in individuals of African and European ancestry. Based on a computational model, predictive values of serum 25(OH)D for individuals of European ancestry (EA), were:

•    35 and 60 nmol/L  (12-24 ng/mL) in the winter, and
•    58 and 85 nmol/L (23-34 ng/mL) in the summer.

For individuals of African ancestry (AA), predictive concentrations of 25(OH)D were:

•    24 and 42 nmol/L  (approx.10-17 ng/mL) in the winter, and
•    40 and 60 nmol/L (16-24 ng/mL) in the summer.

The study researchers concluded that in order to reach a more optimal level of 75 nmoL/L (30 ng/mL) of serum 25(OH)D individuals of EA ancestry with high sun exposure need 1300 IU/d vitamin D intake in the winter, whereas individuals of AA ancestry with low sun exposure “need 2100-3100 IU/day year-round.” (14)

Bear in mind, that the recommended level of 75 nmol/L (30 ng/mL) of serum 25(OH)D in the study above represents what many vitamin D researchers consider to be the low end of optimal 25(OH)D serum concentrations. As I pointed out earlier, the American Journal of Clinical Nutrition’s July 2006 issue opined that the best range of 25(OH)D to be 90 to 100 nmol/L (36–40 ng/mL).” Other pioneer proponents of higher vitamin D3 intake are similarly recommending target serum values of 100 nmol/L (40 ng/mL) of 25(OH)D to 125 nmol/L  (50 ng/mL), and up to 80 ng/mL (200 nmol/L) . Consistent serum levels of 200 ng/mL (500 nmol/L) are considered toxic (see table 3 below).

If all the values of ng/mL and nmol/Ls have you a little dizzy, here is a table that summarizes the severe deficiency to optimal levels referred to above.

Table 3

* Dietary Supplement Fact Sheet: Vitamin D

Office of Dietary Supplements • National Institutes of Health

You Need Vitamin K With It

With the compelling evidence building toward higher intakes of vitamin D3, based on optimal circulating levels of 25(OH)D, it is paramount to one’s health and longevity to evaluate their vitamin D status. Not to be overlooked in considering optimal intakes of vitamin D, is the importance of supplementing with vitamin K with it. You need plenty of vitamin K (Tri-K) with vitamin D supplementation to ensure the benefits to bone health, and for protecting cardiovascular health. Vitamin D optimizes biological calcium levels, while vitamin K acts as the traffic cop, directing calcium into bone tissue, and away from vascular tissue.

I am convinced that research on vitamin K that has been emerging that past few years will have the same recognition in the prevention of age related diseases, as what we are seeing regarding vitamin D3 supplementation today. Optimal vitamin K levels in the body is linked not only to bone and cardiovascular health, but to glucose metabolism, immune system, and brain health benefits as well.

Look for a vitamin D3 product that has vitamin K added to it. Vitamin D Synergy, and Vitamin D Supreme from Designs for Health are products that I recommend and use in my practice.  Read Part 2 of my vitamin D & K article to understand why vitamin K is so important by clicking here.

* Type of study design is comprised of a group of people (cohort) who share a common characteristic (i.e. vitamin D deficiency) or experience within a defined period.

**All Cause  Mortality: Cause-Specific Mortality Rates

*** A type of study in which individuals are observed or certain outcomes is measured. No attempt is made to affect the outcome (for example, no treatment is given).

**** Dietary Reference Intakes (DRIs) are a comprehensive set of nutrient reference values set up by the Food and Nutrition Board (FNB) through a review process overseen by the Institute of Medicine (IOM) of the National Academies, which is an independent, nongovernmental body in the United States. Dietary Reference Intakes or DRIs is an umbrella term that describes types of nutrient intake reference values. They include:

• Recommended Dietary Allowance (RDA):average daily level of intake sufficient to meet the nutrient requirements of nearly all (97%-98%) healthy people.
• Adequate Intake (AI): established when evidence is insufficient to develop an RDA and is set at a level assumed to ensure nutritional adequacy.
• Tolerable Upper Intake Level (UL): maximum daily intake unlikely to cause adverse health effects

For vitamin D, only an AI and UL were established.  For more information, go to:  
http://dietary-supplements.info.nih.gov/factsheets/vitamind.asp

References

1. Low serum 25-hydroxyvitamin D concentrations are associated with greater all-cause mortality in older community-dwelling women
R.D. Semba, D.K. Houston, L. Ferrucci, A.R. Cappola, K. Sun, J.M. Guralnik, L.P. Fried

Nutrition Research  Volume 29, 525-530

2. Independent association of low serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels with all-cause and cardiovascular mortality.
Dobnig H, Pilz S, Scharnagl H, et al.

Arch Intern Med 2008; 168:1340-1349.

3. Vitamin D and systemic cancer: is this relevant to malignant melanoma?
Osborne JE, Hutchinson PE

Br J Dermatol 2002;147:197–213.

4. Scientific documentation of the relationship of vitamin D deficiency and the development of cancer.
Edlich R, Mason SS, Chase ME, Fisher AL, Gubler K, Long WB 3rd, Giesy JD, Foley ML.

J Environ Pathol Toxicol Oncol. 2009;28(2):133-41.

5. Relationship between serum 1,25-dihydroxyvitamin D and mortality in patients with pre-dialysis chronic kidney disease.
Inaguma D, Nagaya H, Hara K

Clin Exp Nephrol 2008;12:126 –31.

6. Vitamin D levels and early mortality among incident hemodialysis patients. Wolf M, Shah A, Gutierrez O, et al

Kidney Int 2007; 72: 1004–13.

7. Resurrection of vitamin D deficiency and rickets
Michael F. Holick

J. Clin. Invest. 116(8): 2062-2072 (2006).

8. Symposium: Vitamin D Insufficiency: A Significant Risk Factor in Chronic Diseases and Potential Disease-Specific Biomarkers of Vitamin D Sufficiency

“Circulating 25-Hydroxyvitamin D Levels Indicative of Vitamin D Sufficiency: Implications for Establishing a New Effective Dietary Intake Recommendation for Vitamin D1″
Bruce W. Hollis

The American Society for Nutritional Sciences J. Nutr. 135:317-322, February 2005

9. The American Society for Nutritional Sciences J. Nutr. 135:317-322, February 2005 Symposium: Vitamin D Insufficiency: A Significant Risk Factor in Chronic Diseases and Potential Disease-Specific Biomarkers of Vitamin D Sufficiency

“Vitamin D Insufficiency in North America”
David A. Hanley and K. Shawn Davison

The American Society for Nutritional Sciences J. Nutr. 135:332-337, February 2005

10. Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes.
Heike A Bischoff-Ferrari, Edward Giovannucci, Walter C Willett, Thomas Dietrich and Bess Dawson-Hughes

Am J Clin Nutr. 2006 Jul;84(1):18-28. Human serum

11. 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol.
Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ.

Am J Clin Nutr. 2003 Sep;78(3):496-7.

12. Risk assessment for vitamin D
J.N. Hathcock, A. Shao, R. Vieth, R. Heaney

American Journal of Clinical Nutrition. January 2007, Volume85, Pages 6-18

13. Cod liver oil, vitamin A toxicity, frequent respiratory infections, and the vitamin D deficiency epidemic.
Cannell JJ, Vieth R, Willett W, Zasloff M, Hathcock JN, White JH, Tanumihardjo SA, Larson-Meyer DE, Bischoff-Ferrari HA, Lamberg-Allardt CJ, Lappe JM, Norman AW, Zittermann A, Whiting SJ, Grant WB, Hollis BW, Giovannucci E.

14. Vitamin D Intake Needed to Maintain Target Serum 25-Hydroxyvitamin D Concentrations in Participants with Low Sun Exposure and Dark Skin Pigmentation Is Substantially Higher Than Current Recommendations
Hall LM, Kimlin MG, Aronov PA, Hammock BD, Slusser JR, Woodhouse LR, Stephensen CB.

J Nutr. 2010 Jan 6. [Epub ahead of print]