No doubt about it, aging takes its toll on the body. Like the plumbing in an old house, the cardiovascular system stiffens and clogs, until one day the heart stops or the brain strokes; the mind "fades" as the death of irreplaceable brain cells accelerates; bones thin, weaken, and eventually fracture. These are just some of the extremely complex, degenerative processes that take place as we age, but different as they are, they all have one theme in common: elevated levels of the amino acid homocysteine.

Homocysteine is a byproduct of the metabolism of the essential amino acid methionine, which is found principally in red meat and dairy products. High homocysteine levels have been associated with increased risk of coronary artery disease, high blood pressure, hip and other bone fractures, rheumatoid arthritis, diabetes, and other serious chronic diseases. Although these are all very dangerous diseases, to the degree that they are caused or aggravated by elevated homocysteine levels, they can be remarkably easy to treat by consuming adequate amounts of foods — which is difficult, if not unfeasible — and/or supplements containing folic acid (folate), vitamin B12 (cobalamin), vitamin B6 (pyroxidine), and betaine (trimethylglycine) — which is far more practical. When taken together in sufficient quantities, these nutrients can minimize homocysteine levels.

The latest example of this relationship is a Japanese study published in a recent issue of the high-profile Journal of the American Medical Association.1 Investigating the possible role of folate and vitamin B12 in preventing hip fractures, the researchers administered daily doses of either folate (5 mg/5,000 µg), vitamin B12 (1.5 g/1500 µg), or placebo to 559 patients who had one-sided paralysis (hemiplegia) due to a stroke. The patients were then monitored for 2 years.

Four Times Fewer Fractures

Hip fractures in elderly people, especially those who have suffered a stroke, often occur as a result of frequent falls combined with osteoporosis, the bone thinning disease that results from a variety of factors, including hormonal changes, diet, and disuse. Although the number of falls was similar in both treatment groups in this study, the folate + vitamin B12 group had one-quarter as many fractures as the placebo group (Fig. 1). The number of hip fractures per 1000 patient-years was 10 in the vitamin-treated group vs. 43 in the placebo control group.

Previous studies have identified increased plasma homocysteine levels as an important risk factor for osteoporosis-related fractures.2, 3 For example, in data from the famous, long-running Framingham Study, homocysteine concentrations were nearly 4-fold higher in the highest quartile of fracture risk patients than in the lowest quartile for men and nearly twice as high for women.3

It should come as no surprise, then, that the Japanese researchers in the present study noted that plasma homocysteine levels significantly decreased from baseline in the low-fracture folate + vitamin B12 group compared to the high-fracture placebo group, where homocysteine levels significantly increased (Fig. 2).

The Bone Density Paradox

While osteoporotic fractures are usually associated with a thinning of the bone, as reflected in a reduction in bone mineral density (BMD), homocysteine concentrations seem to be unrelated to BMD.2, 4 Why then would reducing homocysteine levels reduce osteoporosis-related fractures, as they did this study. The solution to this apparent paradox seems to lie in homocysteine's ability to interfere with collagen cross-linking in bone tissue. Collagen cross-links are important for the stability and strength of the collagen network that helps hold bone tissue together. By interfering with the formation of this network, homocysteine increases bone fragility, even though BMD remains normal.5, 6

Osteoporosis in elderly people is commonly associated with hormone alterations (eg, reductions in estrogen and/or testosterone) as well as a lack of adequate dietary intake of calcium and vitamin D. This study demonstrates that dietary folate and vitamin B12 are also essential for strong, healthy bones. But how much is enough? According to the US government's recommendations (RDAs/DRIs ), adults should be able to survive on 400 µg of folate per day and 2.4 µg of vitamin B12 per day.7 Note, however, that the doses used in this study to retard bone fractures were many times higher: 5,000 µg of folate and 1,500 µg of vitamin B12. It's doubtful that lower doses in the RDA/DRI range, as are offered by many commercial multivitamin formulations or dietary fortifications would be very useful for preserving bone strength.

Optimizing Absorption

A further complication concerns the absorption of folate and vitamin B12 from dietary sources. Both nutrients depend on the presence of normal quantities of stomach acid to free them from their food carriers and optimize absorption. Unfortunately, stomach acid secretion tends to decline with age8 due to atrophic gastritis (or gastric atrophy), a condition in which the stomach cells that secrete digestive acid die off. As the pH in the stomach and intestines rises (due to declining acid levels), folate and vitamin B12 absorption falls off. About 20% to 50% of elderly people are affected by nutrient deficiencies resulting from atrophic gastritis. In addition, many people take drugs such as proton pump inhibitors (PPIs), including Nexium®, Prilosec®, Prevacid®, and others, which reduce the secretion of stomach acid to near zero, further impeding the absorption of folate, vitamin B12, and other nutrients.9, 10 If you're taking any of these drugs, you can be fairly certain you're not absorbing enough folate, vitamin B12, and many other nutrients to preserve your bones. (For a complete discussion on the detrimental effects of low stomach acid levels on nutrient absorption and other health issues, please see the book by Drs. Jonathan V. Wright and Lane Lenard, Why Stomach Acid is Good for You [M. Evans, 2001].9)

Thus, in order to absorb sufficient folate and vitamin B12 it is essential to take supplemental folate and vitamin B12 by a route that bypasses the gastrointestinal (GI) tract. For many years, the only reasonable option was painful injections. Now, however, there are newer, better options that allow nutrients and hormones to enter the bloodstream directly through the skin or mucous membranes.

Jonathan V. Wright, MD, one of the leading alternative and life extension physicians practicing in the United States today has been at the forefront of this effort. One of his most recent innovations has been a liquid formulation of folate and vitamin B12 that can be easily absorbed through the buccal membranes of the mouth — without swallowing. This product is a high-potency liposomal formulation intended to help support healthy bones and more.

Liposomes are artificial microscopic vesicles consisting of an aqueous core enclosed in one or more phospholipid layers, thus mimicking in some ways, natural body cells. Liposomes can be used to convey vaccines, drugs, enzymes, or other substances to target cells or organs. We should also note that, although the Japanese study was conducted in stroke patients, there is no reason to believe that the conclusions drawn from the results should not apply to everyone.


  1. Sato Y, Honda Y, Iwamoto J, Kanoko T, Satoh K. Effect of folate and mecobalamin on hip fractures in patients with stroke: a randomized controlled trial. JAMA. 2005;293:1082-1088.
  2. van Meurs J B, Dhonukshe-Rutten R A, Pluijm S M, et al. Homocysteine levels and the risk of osteoporotic fracture. N Engl J Med. 2004;350:2033-2041.
  3. McLean R R, Jacques P F, Selhub J, et al. Homocysteine as a predictive factor for hip fracture in older persons. N Engl J Med. 2004;350:2042-2049.
  4. Browner W S, Malinow M R. Homocyst(e)inaemia and bone density in elderly women. Lancet. 1991;338:1470.
  5. McKusick V. Heritable Disorders of Connective Tissue, 3rd ed. St. Louis, MO: Mosby; 1966.
  6. Jackson S H. The reaction of homocysteine with aldehyde: an explanation of the collagen defects in homocystinuria. Clin Chim Acta. 1973;45:215-217.
  7. Food and Nutrition Information Center. Dietary Reference Intakes: Vitamins. Accessed March 21, 2005.
  8. Krentz K, Jablonowski H. In: Hellemans J, Vantrappen G, eds. Gastrointestinal Tract Disorders in the Elderly. Edinburgh: Churchill Livingstone; 1984:62-69.
  9. Wright JV, Lenard LG. Why Stomach Acid Is Good for You. New York: M. Evans; 2001.
  10. Wolters M, Strohle A, Hahn A. Cobalamin: a critical vitamin in the elderly. Prev Med. 2004;39:1256-1266.

Featured Product

FREE Subscription

  • You're just getting started! We have published thousands of scientific health articles. Stay updated and maintain your health.

    It's free to your e-mail inbox and you can unsubscribe at any time.
    Loading Indicator