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Life Extension Magazine

LE Magazine August 2001

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Support for supplementation

Such findings build a strong case for encouraging people to meet their daily requirements of B vitamins. As it stands, though, the average intake among the US adult population is 200 micrograms of folic acid. And food sources, particularly with regards to folic acid, fall short of supplying what the body needs, since only about 50% of it may be bioavailable.(14) As a recent study established, synthetic folic acid from fortified foods or supplements is 1.7 times more bioavailable than food-source folate, which means 100 micrograms of folic acid being equivalent to 170 micrograms of food folate.(15) Moreover, individuals with malabsorption problems, be it from a genetic glitch, gastrointestinal diseases, age or existing cardiovascular disease, may need to step up their daily intake through supplementation just to meet the recommended daily allowance. A researcher at Emory University, Atlanta, GA, Godfrey P. Oakley, Jr., MD, MSPM, even argues that “approximately 70% of the adult population in the United States is exposed to a risk factor for cardiovascular disease—an elevated plasma homocysteine concentration—that can be easily avoided simply by consuming a B vitamin supplement.”(16)

The need for a higher intake

B Vitamins’ Multiple Benefits

An Australian study suggests that folic acid plays a critical role in heart disease prevention by stopping chromosome breakage and hypomethylation of DNA.(1) Vitamin B12 levels also aid this purpose by facilitating methionine synthase activity, but low vitamin B12 status compromises this important activity. Likewise, folate deficiency causes “exp-ression of chromosomal fragile sites, chromosome breaks, excessive uracil in DNA, micro-nucleus formation and DNA hypomethylation.” The authors suggest, though, that con-centrations over and above the current RDIs, meaning more than 200 to 400 micrograms of folic acid per day, and more than 2 micrograms vitamin B12 per day, may be crucial for “those with extreme defects in the absorption and metabolism of these vitamins, for which aging is a contributing factor.”

1. Fenech M. Mutat Res 2001 Apr 18;475(1-2):57-67.

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Of course, some experts argue that the current RDA range may not be high enough to ward off heart disease. Consider that a study review of data and findings from 1966 through 1999 by researchers at Ohio State University reported that studies have demonstrated that using 650 micrograms per day of folic acid brought elevated levels of homocysteine back down to a normal range after just two weeks of treatment.(17) Moreover, when Harvard University researchers tracked more than 80,000 female nurses over a 14-year period, they found that a higher intake of folic acid and vitamin B6 exceeding the recommended daily allowance could help cut the risk of heart disease in half. The female participants were given about 700 micrograms of folate and 4.6 milligrams of B6 per day. The investigative team concluded that it might be prudent to suggest to women that they increase their intake of folate and vitamin B6 above the current recommended dietary allowance for the purpose of staving off heart disease.(18)

Nonetheless, many studies to date do suggest that at the very least we attempt to fulfill the daily requirements as currently approved by the FDA. Two recent studies published in the American Journal of Clinical Nutrition, which examined modifiable lifestyle factors for the prevention of heart disease and stroke, revealed that vitamin supplementation, particularly with folic acid, significantly brought down homocysteine levels. One study consisted of offspring and their spouses aged 28 to 82 years old, of the original Framingham Heart Study, which was initiated in 1950. In this group, significantly lower homocysteine levels were evident in those who regularly took vitamin B supplements, as opposed to those who didn’t.(19)

The second study reported similar findings with regards to moderation and supplementation. Called the New Mexico Aging Process Study, it involved 278 elderly subjects ages 66 to 94. Results from that research, as well as many other studies, show that total folate intake is inversely related to homocysteine concentrations in the blood. More specifically, though, while food folate had a negative dose-response relationship to homocysteine levels, supplements containing folate and vitamin B12 led to levels that were 1.5 micromoles/liter lower than in non-users and independent of food source folate intake.(20)

When folic acid is used in conjunction with vitamins B6 and B12, the results are even more impressive. As a number of studies have demonstrated, treatment with a combination of folic acid, vitamin B6 and vitamin B12 not only reduces plasma homocysteine levels, but also restores endothelial function and undoes arterial plaque.(21) A Canadian double-masked, randomized, multicenter clinical trial, called the Vitamin Intervention for Stroke Prevention (VISP) study is currently underway to assess whether high-dose folic acid, vitamin B6 and vitamin B12 supplementation can aid in the reduction of recurrent stroke compared to a lower intake of these vitamins.

And another study by researchers at the USDA’s Human Nutrition Research Center on Aging at Tufts University, Boston, MA, showed that “multivitamin/mineral supplementation can improve B-vitamin status and reduce plasma homocysteine concentration in older adults already consuming a folate-fortified diet.”(22) The randomized, double-blind, placebo-controlled trial included 80 men and women aged 50 to 87 with elevated homocysteine (more than or equal to 8 micromoles/liter), who received either a multivitamin & mineral supplement or placebo for eight weeks (56 days) while consuming their usual diet. At follow-up, subjects taking the supplement had significantly higher B-vitamin status and lower homocysteine concentration than controls. Among those who took a daily supplement, plasma folate, pyridoxal phosphate (PLP) and vitamin B12 concentrations rose by 41.6%, 36.5% and 13.8%, respectively, while the average homocysteine concentration decreased by 9.6%. No such positive changes in terms of improved vitamin status and a related drop in homocysteine levels were reported for the placebo group.

What the government recommends is inadequate

The real take-home message from all of these emerging findings is to take stock of your supplement program—it may be the cheapest and simplest strategy in the fight against heart disease and stroke. The quantity of B vitamins needed to fully protect against vascular disease is significantly greater than the government’s “Dietary Reference Intakes” (formerly called the Recommended Daily Allowance).

The government, for instance, states that only a few milligrams a day of vitamin B6 are needed to stay healthy, yet to significantly lower homocysteine levels, between 100 and 1000 mg of B6 is often required.
The government says only a few micrograms of vitamin B12 are needed to remain alive, yet consuming more than 500 micrograms a day of B12 can greatly assist folic acid in reducing homocysteine concentrations.

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Harvard University researchers tracked more than 80,000 female nurses over a 14-year period. They found that a higher intake of folic acid and vitamin B6 exceeding the recommended daily allowance could help cut the risk of heart disease in half.

The government states that 200 mcg of folic acid is adequate, yet published studies show that doses of between 400 to 5,000 micrograms of folic acid are optimal for cardiovascular disease risk reduction.

The only way of knowing exactly how many B vitamins you need to reduce your homocysteine to a safe range (below 7 micro mol per liter of blood) is to take a homocysteine blood test. If your homocysteine levels are above 7, despite the vitamin supplement regimen you are following, this means you should consider taking more folic acid, vitamins B12 and B6 and adding trimethylglycine (TMG). The FDA has approved TMG as a drug to lower homocysteine in those who have a genetic defect that causes the excess accumulation of homocysteine. Reducing one’s dietary intake of methionine-rich foods such as meat will also facilitate a lower homocysteine level.


References

1. Chao CL, et al. Am J Cardiol 1999 Dec 1;84(11):1359-1361, A8.

2. Chambers JC, et al. Circulation 2000 Nov 14;102(20):2479-2483.

3. Undas A, et al. Thromb Res 1999 Sep 15;95(6):281-288.

4. Newman PE. Med Hypotheses 1999 Nov;53(5):421-424.

5. Arch Int Med 2000;160(21):3258-3262.

6. Morrison, HI, et al. JAMA 1996;275(24):1893-1896.

7. Verhoef P, et al. Eur Heart J 1999 Sep;20(17):1234-1244.

8. Bunout D, et al. Nutrition 2000 Jun;16(6):434-438.

9. Krajcovicova-Kudlackova M, et al. Scand J Clin Lab Invest 2000 Dec;60(8):657-664.

10. VanderJagt DJ, et al. J Natl Med Assoc 2000 Jul;92(7):334-340.

11. Gilbert, SO, et al., Circulation 1998;97:421-424.

12. Sydow K, et al. Z Cardiol 2001 Jan;90(1):1-11.

13. Booth GL, et al. CMAJ 2000 Jul 11;163(1):21-29.

14. Riddell LJ, et al. Am J Clin Nutr 2000;71:1448-1454.

15. Nutr Rev 1998 Oct;56:294-299.

16. NEJM 1999 Sep 16;341(12).

17. Temple ME, et al. Ann Pharmacother 2000 Jan;34(1):57-65.

18. Rimm, EB, et al. JAMA 1998 Feb 4;279(5):359-364.

19. Jacques, PF, et al., Am J Clin Nutr 2001;73:613-621.

20. Koehler, KM, et al. Am J Clin Nutr 2001;73:628-637.

21. Spence J, et al. Neuroepidemiology 2001 Feb;20(1):16-25.

22. McKay DL, et al. J Nutr 2000 Dec;130(12):3090-6.


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