Saturday, November 26, 2005

Paradigms and Paradoxes about Vitamin D

Reprinted from...
John Cannell, MD The Vitamin D Council

Last month, Dr. Armin Zittermann, of Ruhr University in Germany, published the best vitamin D paper of the month. He reviewed the mounting evidence that vitamin D deficiency is a major cause of heart disease.
Br J Nutr. 2005 Oct;94(4):483-92.

Before we start, let’s talk about paradigms and paradoxes. A paradigm is a set of assumptions, concepts, and practices that constitutes a way of viewing reality. The current paradigm is that heart disease is caused by a combination of genetics, hypertension, diabetes, cholesterol, smoking, obesity, inactivity, and diet. A paradox is a fact that contradicts the paradigm.

The Framingham Risk Equation is an attempt to use the most reliable risk factors in the paradigm to predict who will get heart disease. When they applied it to British men for ten years, they found 84% of the heart disease occurred in the men classified as low risk! Furthermore, 75% of the men classified as high risk were still free of heart disease ten years later. It seems the equation is missing a few variables.
BMJ. 2003 Nov 29;327(7426):1267.

There are several interesting heart disease paradoxes. How well do you know them? Good time for another quiz.

1. The French Paradox is the observation that cardiovascular disease is relatively low in France, despite high intakes of saturated fats.

A. True
B. False

True. Perhaps the best known of the cardiovascular disease paradoxes, the most common explanation is that the French love red wine and the antioxidants it contains. It was first described in 1987, before the dermatologists scared the French out of their bikinis. The rates of cardiovascular mortality in France are much lower in the South and West than in the North. One of the world’s best vitamin D researchers, Dr. Marie Chapuy, found that vitamin D levels of healthy adults in France follow that same pattern, with a mean level of 38 ngs/ml in the sunnier and drier South and West, but less than half that (17ngs/ml) in the colder, rainier, and more polluted, North.
Arch Mal Coeur Vaiss. 1987 Apr;80 Spec No:17-21.
Hypertension. 2005 Oct;46(4):645-6. Epub 2005 Sep 12.
Hypertension. 2005 Oct;46(4):645-6. Epub 2005 Sep 12.
Osteoporos Int. 1997;7(5):439-43.

2. The Israeli Paradox is the observation that cardiovascular disease is high in Israel despite a high consumption of polyunsaturated omega-6 fats.

A. True
B. False

True. According to the current paradigm, polyunsaturated fats contained in vegetable seed oils are supposed to lower the risk of heart disease. However, high consumption of these oils doesn’t appear to prevent the Israelis from dying from heart attacks. Israel does, despite its sunny weather, have a high incidence of vitamin D deficiency. Average vitamin D levels among healthy adults in Lebanon, right next door, are only 9.7 ngs/ml - dangerously low. Healthy Jewish mothers, especially orthodox ones, have low vitamin D levels. (If you are wondering how the pro-inflammatory omega-6 oils could ever help heart disease, one possibility is these oils dissociate vitamin D from its binding protein, making more free vitamin D available. Apparently, the Israelis don’t have enough vitamin D in their blood to dissociate).
Isr J Med Sci. 1996 Nov;32(11):1134-43.
Isr Med Assoc J. 2004 Feb;6(2):82-7.
J Bone Miner Res. 2000 Sep;15(9):1856-62.
Isr Med Assoc J. 2001 Jun;3(6):419-21.
J Steroid Biochem Mol Biol. 1992 Sep;42(8):855-61.

3 The Italian Paradox is the observation that a population of heavy smokers has a low incidence of cardiovascular disease.

A. True
B. False

True. The overall death rate from cardiovascular disease in Italy, a country of heavy smokers, is relatively low. Before you say it is the olive oil and wine, ask yourself where olive trees and grapevines grow – in the sun. However, at least two good studies show vitamin D levels in Europe are a paradox, the closer a European lives to the equator, the lower their vitamin D level. Nevertheless, an Italian study showed healthy Roman blood donors had robust vitamin D levels of 48 ngs/ml in the summer. Even average postmenopausal Italian women reached 36 ng/ml in the summer. Anyone who has traveled in Italy, know that most Italians love the sun. As the old Italian proverb points out: “Where the sun does not go, the doctor does.”
QJM. 2000 Jun;93(6):375-83.
Br J Nutr. 1999 Feb;81(2):133-7.

4. The Northern Ireland Paradox is the observation that a population with a very high incidence of coronary heart disease does not have high rates of the expected risk factors.

A. True
B. False

True. In fact, the age adjusted mortality for coronary artery disease was more than four times higher in Belfast than in Toulouse, France, despite almost identical coronary risk factors. There were 761 deaths per 100,000 in Belfast compared to 175 in Toulouse. This is hard to explain, given the current paradigm of heart disease. Of interest, Belfast is at 54 degrees latitude, at sea level, and has 257 rainy days per year. Toulouse is eleven degrees closer to the equator, its altitude is 500 feet closer to the sun, and Toulouse only has 74 rainy days per year. Lots more vitamin D in Toulouse!
QJM. 1995 Jul;88(7):469-77.
QJM. 1998 Oct;91(10):667-76.
Weatherbase, Belfast
Weatherbase, Toulouse

5. The Indian Paradox is the observation that a high prevalence of coronary artery disease in urban Indians is associated with low saturated fat intake.

A. True
B. False

True. Researchers found that a low saturated fat diet did not prevent heart disease in the citizens of the brass-works-polluted city of Moradabad in northern India. The authors did not mention that air pollution dramatically lowers vitamin D levels.
J Am Coll Nutr. 1998 Aug;17(4):342-50.
Arch Dis Child. 2002 Aug;87(2):111-3.

6. The Swedish Paradox is the observation that the strong association between cold weather and heart disease in Sweden is not explained by the usual risk factors.

A. True
B. False

True. Researchers tried to explain why higher annual cardiac mortality is associated with residence in colder regions of Sweden. Try as they might, the authors could not support the current paradigm for heart disease. They failed to mention that cold weather is a marker for low vitamin D levels, as outdoor activity in cold weather is both curtailed and requires extensive clothing.
Scott Med J. 1991 Dec;36(6):165-8.

The point of these six paradoxes is simple. Our current paradigm for understanding heart disease is incomplete. One or more major causes of heart disease remain unknown. One theory - the theory that vitamin D deficiency is a major cause of heart disease – may explain these paradoxes.

7. Robert Scragg, Associate Professor in Epidemiology at the University of Auckland, first proposed that vitamin D deficiency plays a role in cardiovascular disease.

A. True
B. False

True. For the last 25 years, Dr. Scragg has been trying to convince anyone who would listen that vitamin D explains many of observations about heart disease. These include the facts that heart disease is higher at higher latitudes, lower altitudes, in the winter, in African Americans, in older, inactive, and in more obese patients. Remember, vitamin D blood levels are lower at higher latitudes, lower altitudes, in the winter, in African Americans, in older, inactive, and in more obese patients. Altitude is the least known of these associations. The age adjusted mortality for heart disease in the USA showed a striking inverse correlation with altitude in 1979, before the sun scare. American populations at the highest altitude had about half the heart disease of sea level populations. Thirty-five years ago, Leaf observed that most of the long-lived populations in the world reside at high altitude.
Int J Epidemiol. 1981 Dec;10(4):337-41.
J Chronic Dis. 1979;32(1-2):157-62.
Sci Am. 1973 Sep;229(3):44-52.

8. Dr. Scragg showed that higher vitamin D levels are associated with lower risk for heart attack.

A. True
B. False

True. In 1979, the Tromso Heart Study found corrected vitamin D levels showed the same thing.
Int J Epidemiol. 1990 Sep;19(3):559-63.
Br Med J. 1979 Jul 21;2(6183):176.

9. Dr. Scragg is such a good scientist, he then published a study which seemed to disprove his theory.

A. True
B. False

True. He discovered that a single oral dose of 100,000 units of vitamin D had no effect on risk factors (serum cholesterol or blood pressure) five weeks later. This seemed to disprove his theory, but he published the data anyway, always a mark of a good scientist. We now know that 100,000 units are a small dose and that such “stoss” therapy is not physiological. Such a small single dose will raise vitamin D levels for a month or two, but then they rapidly fall towards baseline and would have little physiological effect five weeks later.
Eur J Clin Nutr. 1995 Sep;49(9):640-6.

10. Zittermann points out that vitamin D reduces vascular smooth muscle proliferation, reduces vascular calcification, decreases parathormone levels, reduces C reactive protein (CRP) and other markers of inflammation, and decreases renin, all of which should prevent or treat heart disease.

A. True
B. False

True. He discusses most of the evidence that exists, tying heart disease to vitamin D deficiency. A vitamin D theory of heart disease explains the excess cardiovascular deaths at high latitude, low altitude and during the winter. Furthermore, it explains the higher incidence of heart disease in African Americans, older, inactive, and obese individuals as these groups have significantly lower vitamin D blood levels.
Br J Nutr. 2005 Oct;94(4):483-92.

11. In 2003, Zittermann discovered that patients with congestive heart failure (CHF) have very low levels of vitamin D.

A. True
B. False

True. Furthermore, he found that a protein (NT-proANP), which is a predictor of CHF severity, was inversely associated with vitamin D levels.
J Am Coll Cardiol. 2003 Jan 1;41(1):105-12.

12. Blood cholesterol measurements are worse at higher latitudes, lower altitudes and in the winter.

A. True
B. False

True. The effects of latitude on cholesterol seen in the first study are quite remarkable. In the Greek study, total serum cholesterol for both men and women were significantly lower at higher altitude in spite of similar diets. The seasonal variations in cholesterol are well known and not explained by seasonal dietary changes.
QJM. 1996 Aug;89(8):579-89.
J Epidemiol Community Health. 2005 Apr;59(4):274-8.
J Clin Epidemiol. 1988;41(7):679-89.
Chronobiol Int. 2001 May;18(3):541-57.

13. Blood pressure is higher at higher latitudes, lower altitudes, in the winter, in African Americans, in the aged, and in the obese.

A. True
B. False

True. High blood pressure is one of the strongest predictors of heart disease. Here, six facts about hypertension can be explained by one theory: vitamin D.
Hypertension. 1997 Aug;30(2 Pt 1):150-6.
Ann Hum Biol. 2000 Jan-Feb;27(1):19-28.
Harv Health Lett. 2005 Sep;30(11):8.

14. Diabetes is more common at higher latitudes, at lower altitudes, in African Americans, in the aged and the obese. Both blood sugar and hemoglobin A1C are higher in the winter.

A. True
B. False

True. Six final facts that can be explained with one theory: vitamin D.
Eur J Epidemiol. 1991 Jan;7(1):55-63.
Nutrition. 2001 Apr;17(4):305-9.
Diabetes Res Clin Pract. 2005 Aug;69(2):169-74. Epub 2005 Jan 12.
Diabetologia. 1982 Apr;22(4):250-3.
Am J Epidemiol. 2005 Mar 15;161(6):565-74.

15. Two studies show vitamin D significantly reduces C reactive protein (CRP), which may be a better predictor of heart disease than LDL cholesterol.

A. True
B. False

True. The Belgian study found a significant effect on CRP even though their high-dose vitamin D group only got 500 units a day.
QJM. 2002 Dec;95(12):787-96.
J Clin Endocrinol Metab. 2003 Oct;88(10):4623-32.

16. The risk for total mortality is significantly lower in subjects with high vitamin D levels.

A. True
B. False

True. However, the study is in Finnish and has not been translated into English (author communication).
Seppanen R, Marniemi J, Alanen E, Impivaara O, Jarvislo J, Ronnemaa T, et al. Ravinnon ja seerumin vitamiinit ja kivennaisaineet vanhusten kuolleisuuden ennustajina. Suom Laakaril 2000;42:4255-60 [Finnish]. Reported in Nutr Metab Cardiovasc Dis. 2005 Jun;15(3):188-97.

17. It is now a proven scientific fact that vitamin D both prevents and treats heart disease.

A. True
B. False

False. Like so may other fields of vitamin D research, we lack the definitive interventional trials that would settle the point. It would be simple for the National Institutes of Health to fund a study giving physiological doses of real vitamin D (5,000 units of cholecalciferol) to heart disease patients for a year and see if CRP, proinsulin, blood pressure, cholesterol, body weight, heart attacks, or death rate decreases.

We will have to wait years for science to find out if vitamin D prevents and/or treats heart disease. While you are waiting, you have a choice. You can wait vitamin D deficient (levels less than 40 ngs/ml) or you can wait vitamin D sufficient (levels around 40-60 ngs/ml). The choice is yours - another Pascal’s Wager - this time you are betting your heart.

Also, while you wait for more studies, remember that vitamin D should be obtained daily, not monthly or weekly. It should be obtained physiologically, not in an all-then-none manner, as would happen if you took 100,000 units one day a month and nothing the other 29 days. It appears likely that high blood levels followed by low blood levels may do harm. The reason is that falling blood levels reset the enzymes maintaining intracellular levels of activated vitamin D, resulting in low intracellular levels.
Int J Cancer. 2004 Sep 1;111(3):468; author reply 469.

Vitamin D should be consumed the way the human genome consumed it during its evolution in subequatorial Africa, a steady amount every day. If you live down south, you can go in the sun for a few minutes every day. If you live up north you can sun in the warmer months and use a sunlamp or take real vitamin D (cholecalciferol) in the winter. Adults in the north could take one 5,000 unit capsule a day in late fall, winter, and early spring, less in the late spring and early fall, and none in the summer months - depending on your sunning habits. Children over 50 pounds need two of the 1,000 unit capsules every day in the colder months while children under 50 pounds need about 1,000 units in the colder months. Few people need to take oral vitamin D in the summer unless you are a sunphobe. Get enough vitamin D every day to maintain stable vitamin D blood levels (25-hydroxy-vitamin D) around 50 ngs/ml, year-around.

Last question: should patients dying from heart disease be allowed to die vitamin D deficient? According to the current paradigm, the answer is yes. At least, none of the cardiologists I know even bother to check a vitamin D level. Given the scientific literature, that’s a bit paradoxical.

Comment: Don't wait for final proof, do it...

Vitamin D3


Christopher Wiechert's Healthblogger is for educational or informational purposes only, and is not intended to diagnose or provide treatment for any condition. If you have any concerns about your own health, you should always consult with a healthcare professional. If you decide to use this information on your own, it's your constitutional right, but I assume no responsibility.
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