Homocysteine: A new theory about old bones
The new theory of osteoporosis is the homocysteine theory. Homocysteine is an amino acid that is a by-product of the metabolism of protein in the body. It is toxic; so the body has three pathways to convert it into non-toxic substances. If you’ve heard of homocysteine, it was probably in connections with heart disease.
The Homocysteine theory of heart disease
The homocysteine theory of heart disease grew out of observing people with the genetic disease of homocystinuria, in which homocysteine rises to very high levels because of enzyme deficiencies. Children born with this disease usually die before the age of 20, often in early childhood and even infancy, from heart attacks and strokes resulting from severe arteriosclerosis. The arteriosclerosis is the same as that occurring in people in their 60s, 70s, 80s, and 90s. According to the homocysteine theory, this arteriosclerosis of middle and old age is also caused by elevated levels of homocysteine.
But what could cause elevated homocysteine levels in people who do not have genetic enzyme deficiencies? The answer: vitamin deficiencies. The enzymes that rid the body of homocysteine are activated by coenzymes. These coenzymes are vitamins – vitamin B6, folic acid, and vitamin B12.
If any of these three vitamins are deficient of lacking, the enzymes will not be able to function optimally even if there is no inherited enzyme defect; and, as a consequence, homocysteine will rise above normal levels.
The homocysteine theory in a nutshell: if severely high levels of homocysteine resulting from a genetic defect could destroy a child’s arteries, milder but more chronic elevations over the course of a lifetime of 30 or 40 or 50 or more years resulting from a vitamin B deficient diet could cause cardiovascular disease in adults who do not have the genetic disease of homocystinuria. The standard American diet is just such a vitamin B deficient diet.
The Homocysteine theory of Osteoporosis
The same reasoning is behind the homocysteine theory of osteoporosis because children with homocystinuria also have osteoporosis in childhood, the same osteoporosis that afflicts people in the general population in their 60s, 70s, 80s, and 90s.
Two studies, both appearing in the May 13, 2004, New England Journal of Medicine, now provide strong evidence in support of this theory. They were significant enough at the time to make the news: Time magazine, May 24, 2004 and MSNBC, May 18, 2004.
In one of the studies, scientists analyzed blood samples obtained and stored from 1,999 men and women between 1979 and 1982 as part of the long-term Framingham study. The researchers found that men with the highest homocysteine levels were four times as likely to develop hip fractures as men with the lowest levels. Women with the most homocysteine were about twice as likely to break a hip as were women with the least. The study recorded bone breaks in men for an average of 12 years and in women for an average of 15 years.
The second study, from researchers at Erasmus University in the Netherlands, analyzed blood samples from 2,406 people. Men and women with the highest levels of homocysteine had twice the risk of suffering a fracture compared to those with the lowest levels. The study checked for bone breaks for periods ranging from about 3 years to 8 years.
Bone density vs. bone quality
Curiously, the Dutch team found that people with the highest and lowest homocysteine readings didn’t have appreciatively different bone densities, even though the high homocysteine group had more fractures. One reason might be that bone density fails to capture a poorly understood factor known as bone quality, which declines with age, researchers say.
“A 50-year old woman with a bone density that is clearly in the osteoporotic range has a much lower risk of having a fracture in the next year or next five years than an 80-year-old woman with the same bone density,” said Dr. Joan McGowan, chief of the musculoskeletal diseases branch at the National Institute of Arthritis and Musculoskeletal and Skin Diseases. “It’s definitely something about the quality of bone changing.”
Homocysteine could weaken bones by affecting bone quality rather than bone density. One way it might do this is by its effect on collagen. Both groups of researchers point to homocysteine’s effect on collagen as a possible explanation for their findings. Collagen is the chief protein in bone, ligaments, tendons, skin and other connective tissue. Test-tube studies have indicated that homocysteine interferes with bonding between collagen fibers that reinforce those tissues.
The collagen fibers in skin samples of people with homocystinuria are not tightly linked, notes Joyce B. J. van Meurs, the lead author of the Dutch study. “Cross-linking is important for the strength of the collagen network,” van Meurs said. “If it is disturbed, you will have less stability,” which could lead to more fractures.
What can you do to protect yourself? Total homocysteine concentrations can be effectively and easily modified by dietary intake of folic acid and vitamins B6 and B12. Next week’s article will be on these three vitamins and their effect on bones.
Mary Lou Williams, M. Ed., is a lecturer and writer in the field of nutrition. She welcomes inquiries. She can be reached at 267-6480.