Flawed Analysis Misleads Public re Calcium

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From: lifeextension@...(Life Extension) Date: Tue, Aug 10, 2010,

3:08am

Flawed Analysis Misleads Public About

Calcium and Heart Attack Risk

The media is at it again — reporting deceptive propaganda by the

medical establishment as if it were scientific fact.

Just imagine the epidemic of osteoporosis that will occur if women stop

taking their calcium supplements. That will happen if the public relies

on mainstream news reporters to make their health decisions.

In a biased and horrifically flawed analysis, a group of doctors came to

the conclusion that calcium supplements increase heart attack risk by

27%.

Omitted from the media reports were critical facts such as the exclusion

of people who took vitamin D, magnesium or other nutrients typically

found in bone protection formulations.

In other words, calcium-supplemented study subjects (who the mainstream

claims suffered higher heart attack rates) would have been seriously

deficient in vitamin D and magnesium — two essential nutrients that

protect against heart attack.

The doctors who compiled this analysis also conveniently omitted major

clinical trials showing that those with higher calcium intake had

significantly lower cardiovascular rates.

A technical rebuttal by Joyal, M.D., to this flawed study appears

below. We do want to emphasize, however, the critical need to supplement

with other nutrients when taking calcium for optimal effect.

As we age, the body's internal regulators of calcium deposition become

dysfunctional. Scientists have uncovered a deficiency of vitamin K as

being a factor that enables calcium to infiltrate the inner lining of

arteries to cause arterial calcification. By ensuring optimal vitamin K

status, calcium is directed to the bone and away from the arterial wall.

Fortunately, Life Extension® members obtain vitamin K in the Super

Booster multi-nutrient caps as well as Super K capsules.

Magnesium is another critical nutrient for bone and cardiovascular

health. Of interest, magnesium is considered a natural calcium-channel

blocker {Reference: Iseri LT, French JH. Magnesium: nature's physiologic

calcium blocker. Am Heart J. 1984 Jul;108(1):188-93.} that supports

endothelium-dependent relaxation of blood vessels {Reference: Euser AG,

Cipolla MJ. Magnesium sulfate for the treatment of eclampsia: a brief

review. Stroke. 2009 Apr;40(4):1169-75.}. For optimal bone and

cardiovascular health, nutritional experts for the past 40 years have

urged those who take calcium to also supplement with magnesium and

vitamin D. Life Extension members obtain magnesium and vitamin D in the

Bone Restore and other bone-support formulas.

Optimal bone health and protection against atherosclerosis requires a

multifactorial approach that involves far more than taking only calcium,

The recently published meta-analysis, flawed as it is, offers a valuable

lesson to the serious supplement user, i.e. lack of careful scientific

analysis creates seriously flawed conclusions.

Rebuttal to Meta-analysis Claiming that Calcium Increases Myocardial

Infarction (heart attack) Risk

By Joyal, M.D.

On July 30, 2010, a meta-analysis published in the British Journal of

Medicine reported that calcium supplementation was associated with a

significant increase in risk for heart attack. Specifically, of the 11

trials included defined by the authors as having " trial level data, " the

authors reported a 27% increase in relative risk for heart attack in

patients allocated to calcium supplementation (pooled relative risk,

1.27; 95% confidence interval 1.01–1.59, p-value=0.038).

A careful examination of the study methodology reveals several major

flaws that severely compromise the authors' conclusions.

In addition, four of the contributing authors of this meta-analysis were

involved in pharmaceutical development trials involving calcium

supplementation, including Wyeth, Mission Pharmacal, Shire

Pharmaceuticals, and Nycomed.

Alarming levels of vitamin D deficiency and exclusion of trial data

involving vitamin D3 supplementation in combination with calcium

supplementation

The study authors indicate that vitamin D3 supplementation reduces

mortality,1 yet excluded trials that used vitamin D3 in combination with

calcium supplementation vs. a placebo comparator.

In fact, vitamin D deficiency has been shown to increase cardiovascular

risk.2 Careful review of the 11 studies with trial data included by the

authors in the meta-analysis reveals very low levels of 25-hydroxy

vitamin D3, ranging from 18.0 to 37.2 ng/mL.

Based upon the vitamin D insufficiency observed in the trial data

included in this meta-analysis, the finding of an increase in heart

attack risk is not surprising.

Exclusion of several major trials that showed significant reductions in

cardiovascular morbidity and mortality with calcium intake

The Boston nurses health study found that women in the highest fifth for

calcium intake from supplements and diet had an adjusted relative risk

of ischemic stroke of 0.69 (95% confidence interval 0.50 to 0.95)

compared with those in the lowest fifth;3

The Iowa women's health study found a one-third reduction in deaths from

cardiovascular events in women whose calcium intake from supplements and

diet was in the highest fourth compared with those in the lowest

fourth;4

The United Kingdom study of ischemic heart disease and calcium intake

reported higher calcium intake reduced mortality for ischemic heart

disease.5

Lack of consistency with other studies showing reduction in biomarkers

of cardiovascular risk with calcium supplementation

Calcium supplementation, as well as dietary calcium, reduces blood

pressure,6 a major risk factor for heart attack and stroke;

Calcium supplementation increases the ratio of high density lipoprotein

(HDL) cholesterol to low density lipoprotein (LDL) cholesterol by almost

20% in healthy postmenopausal women;7

Calcium supplementation reduces body weight and promotes reductions in

blood pressure in aging women.8

Given the alarming level of vitamin D deficiency observed in the trial

data included in this meta-analysis, the finding of an increase in heart

attack risk is not unexpected. Furthermore, exclusion of a variety of

calcium trials that show beneficial effects on cardiovascular risk (as

well as blood pressure and body weight) suggests author bias.

Lack of appreciation for the critical role of vitamin K in bone and

cardiovascular health

A characteristic of normal aging involves calcification in soft tissues

throughout the body such as heart and blood vessels.9-11

In contrast to the stated conclusion (i.e. calcium supplementation is

associated with an increase in heart attack risk) of the current

meta-analysis, scientific experiments suggest the opposite to be true.

For example, in validated models of atherosclerosis, calcium-deficient

diets increase the rate of tissue calcification by 170% while

calcium-supplemented diets, on the other hand, reduce calcification by

62%.12

The explanation for this apparent contradiction is that in response to

insufficient blood levels of calcium, the body robs our bones13 and,

without adequate vitamin K, saturates the arterial wall with calcium. In

the arterial wall, vitamin K regulates a protein (matrix Gla-protein)

that protects against arterial calcification.

The importance of vitamin K for bone and cardiovascular health was not

discussed, acknowledged, or described by the authors in this

meta-analysis claiming that calcium increases heart attack risk. Vitamin

K is critical to ensure optimal carboxylation of matrix Gla protein

(MGP) in healthy subjects. The majority of MGP in the carotid arterial

lining of patients with atherosclerosis is undercarboxylated.14 Serum

undercarboxylated MGP is decreased in patients at risk of cardiovascular

calcification due to deposition of undercarboxylated MGP in areas of

vascular calcification.15

Most Life Extension® members already obtain high doses of vitamin K in

the Super Booster or Super K formulas.

Health conscious individuals should make sure they are supplementing

with at least 300-500 mg of elemental magnesium each day. Some people

require higher magnesium intake for optimal tissue saturation. Those

with kidney impairment are not always able to safely take higher doses

of magnesium.

References

1. Autier P, Gandini S. Vitamin D supplementation and total mortality: a

meta-analysis of randomized controlled trials. Arch Intern Med. 2007 Sep

10;167(16):1730-7.

2. Wang TJ, Pencina MJ, Booth SL, et al. Vitamin D deficiency and risk

of cardiovascular disease. Circulation. 2008 Jan 29;117(4):503-11.

3. Iso H, Stampfer MJ, Manson JE, et al. Prospective study of calcium,

potassium, and magnesium intake and risk of stroke in women. Stroke.

1999 Sep;30(9):1772-9. 4. Bostick RM, Kushi LH, Wu Y, Meyer KA, Sellers

TA, Folsom AR. Relation of calcium, vitamin D, and dairy food intake to

ischemic heart disease mortality among postmenopausal women. Am J

Epidemiol. 1999 Jan 15;149(2):151-61.

5. Knox EG. Ischaemic-heart-disease mortality and dietary intake of

calcium. Lancet. 1973 Jun 30;1(7818):1465-7.

6. Griffith LE, Guyatt GH, Cook RJ, Bucher HC, Cook DJ. The influence of

dietary and nondietary c alcium supplementation on blood pressure: an

updated meta-analysis of randomized controlled trials. Am J Hypertens.

1999 Jan;12(1 Pt 1):84-92.

7. Reid IR, Mason B, Horne A, et al. Effects of calcium supplementation

on serum lipid concentrations in normal older women: a randomized

controlled trial. Am J Med. 2002 Apr 1;112(5):343-7.

8. Reid IR, Horne A, Mason B, Ames R, Bava U, Gamble GD. Effects of

calcium supplementation on body weight and blood pressure in normal

older women: a randomized controlled trial. J Clin Endocrinol Metab.

2005 Jul;90(7):3824-9.

9. Giachelli CM, Speer MY, Li X, Rajachar RM, Yang H. Regulation of

vascular calcification: roles of phosphate and osteopontin. Circ Res.

2005 Apr 15;96(7):717-22.

10. Jono S, Shioi A, Ikari Y, Nishizawa Y. Vascular calcification in

chronic kidney disease. J Bone Miner Metab. 2006;24(2):176-81.

11. Shao JS, Cai J, Towler DA. Molecular mechanisms of vascular calcifi

c ation: lessons learned from the aorta. Arterioscler Thromb Vasc Biol.

2006 Jul;26(7):1423-30.

12. Hsu HH, Culley NC. Effects of dietary calcium on atherosclerosis,

aortic calcification, and icterus in rabbits fed a supplemental

cholesterol diet. Lipids Health Dis. 2006 Jun 23;5:16.

13. S, Debuse M. Endocrine and Reproductive Systems. 2nd ed.

Elsevier Health Sciences; 2003:89-90.

14. Schurgers LJ, Teunissen KJ, Knapen MH, et al. Novel

conformation-specific antibodies against matrix gamma-carboxyglutamic

acid (Gla) protein: undercarboxylated matrix Gla protein as marker for

vascular calcification. Arterioscler Thromb Vasc Biol. 2005

Aug;25(8):1629-33.

15. Cranenburg EC, Vermeer C, Koos R, et al. The circulating inactive

form of matrix Gla protein (ucMGP) as a biomarker for cardiovascular

calcification. J Vasc Res. 2008;45(5):427-36.

16. Schurgers LJ, Teunissen KJ, Hamulyak K, Knapen MH, Vik H, Vermeer C.

Vitam i n K-containing dietary supplements: comparison of synthetic

vitamin K1 and natto-derived menaquinone-7. Blood. 2007 Apr

15;109(8):3279-83.