In recent years, a number of well-controlled studies have highlighted the importance of optimal B-vitamin status as a means to reduce the risk of heart disease, certain cancers, and inflammatory states; improve detoxification processes; and maintain brain and cognitive function as we age.
B Vitamins Reduce the Risk of Cervical and Colon Cancer
The nutritional status of certain B vitamins has emerged as an important factor in the risk profile for cervical and colon cancer. Folic acid and vitamin B12 are required to help the body convert a compound called homocysteine to methionine. Once formed, methionine is readily converted to S-adenosylmethionine, which is necessary to form the DNA that makes up our genetic blueprints for life.
If folic acid and/or vitamin B12 status become suboptimal, the amount of S-adenosylmethionine declines. This results in an inability to properly produce DNA as cells replace themselves from one generation to the next. The danger is that genetic errors become more common, and genetic linkages become more fragile (hypomethylated DNA) and prone to breakage with resulting mutations. These alterations to genetic structure provide the foundation for cancerous changes to occur in our genes. It is well-established that our DNA is much more prone to cancerous mutations under conditions of suboptimal intake of folic acid and vitamin B12.
Women in a marginal deficiency state of folic acid are known to be prone to cervical dysplasia and cervical cancer. This is related to the fact that the cells which line the cervix replace themselves every 7-14 days, and therefore, must continuously synthesize DNA. Studies have demonstrated that poor folic acid status can lead to DNA abnormalities, with subsequent development of cervical dysplasia or megaloblastic features of cervical cells (large abnormal cell appearance). With respect to cervical dysplasia (a precancerous condition), folic acid, via its role in DNA synthesis and DNA repair, has been shown to inhibit the ability of the human papillomavirus (HPV) from invading the DNA of surface cervical cells. HPV is strongly associated with cervical cancer; thus, folic acid supplementation is an important step to prevent HPV's invasion into cervical tissue. Women who have experienced multiple sex partners are most prone to infection with HPV, as contact with human semen is the way in which cervical cells are typically exposed to the virus.
Oral contraceptives are also known to increase the rate of cell division of cervical cells, thereby increasing the need for adequate folic acid intake. Studies by Whitehead, et al., and Butterworth, et al., have demonstrated that folic acid supplementation can reverse cervical megaloblastic changes and cervical dysplasia, respectively, in patients using oral contraceptives. In fact, oral contraceptive use is a known risk factor for cervical dysplasia, primarily due to its effect on speeding up cell division rates.
In the study by Butterworth, et al., patients with mild and moderate degrees of cervical dysplasia showed reversal of their condition over a three-month trial period with folic acid supplementation at very high levels (5,000-10,000 mg per day). In both studies, the authors noted a statistically lower mean red blood cell concentration of folic acid in oral contraceptive users compared with nonusers, particularly in patients with cervical dysplasia. Other population studies (epidemiological studies) consistently support the research showing that folic acid plays a protective role in the prevention of cervical dysplasia.
Unfortunately, up to 88% of the population consumes less than 400 mcg per day of folic acid. This is the level that women should ingest to reduce the risk of spinal birth defects in their offspring. As it turns out, the same level of folic acid intake appears to be sufficient to reduce the risk of cervical dysplasia.
With respect to colon cancer, Giovannucci and fellow researchers assessed dietary intake for a one-year period in women enrolled in the Nurses' Health Study, and men enrolled in the Health Professional Follow-up Study, using a semi-quantitative and food frequency questionnaire. Of the 25,474 subjects, 895 developed adenomatous polyps of the left colon or rectum.
A major finding of the study was that high folic acid intake was protective against colorectal cancer. Women in the top 20% intake level of folic acid demonstrated a 34% decreased risk of colorectal cancer, compared with women in the bottom 20% intake level of folic acid. For men, a 37% reduction in risk was observed for the highest 20% intake of folic acid versus the lowest 20% intake group. Users of multiple vitamins demonstrated the greatest reduction in the risk of colorectal cancer in this study. Much of this protective effect was shown to be due to folic acid. These findings are consistent with other epidemiological evidence indicating that folic acid reduces the risk of colorectal cancers. It is important to keep in mind that colon cancer is the second leading cause of cancer death in North America.
B Vitamins in the Prevention of Cardiovascular Disease
In regards to the role of B vitamins in the prevention of heart disease and stoke, in the mid-to-late 1960s, several researchers first identified that high blood levels of homocysteine are associated with premature narrowing of arteries, leading to heart attacks and related heart disease. Homocysteine is thought to increase the risk for heart disease through direct toxic effects to the cells that line our blood vessels. It increases the tendency for blood platelet cells to clump together in the bloodstream, thus obstructing blood flow. It also stimulates muscle fibers beneath the blood vessels to grow into the artery, further impairing the flow of blood. A high blood level of homocysteine is now considered to be a significant risk factor for stroke, heart attack, and reduced blood flow to fingers, toes and peripheral body parts.
Homocysteine is formed routinely by the cells of our body during the course of normal metabolism. Fortunately, our bodies can eliminate homocysteine by converting it into other important amino acids such as methionine, cystathionine, serine, and cysteine. However, in order to convert homocysteine into these desirable, nontoxic amino acids, our bodies require an adequate intake of the B vitamins - folic acid, B6 and B12. A number of recent studies have shown that individuals with high blood levels of homocysteine can reduce levels by supplementing their diet with folic acid, vitamin B6 and/or vitamin B12. Presently, elevated blood levels of homocysteine are considered to be responsible for approximately 10% of all heart attacks each year in the United States.
Reporting in the Journal of the American Medical Association (February 1988), Rimm and fellow researchers demonstrated that women who supplemented their diet with a multiple vitamin had a 24% lower risk of nonfatal and fatal heart attacks. During the 14-year follow-up, they documented 658 incident cases of nonfatal heart attacks and 281 cases of fatal heart attacks among the 80,082 women enrolled in the Nurses' Health Study. After controlling for well-known risk factors for heart disease, the researchers showed that high intake levels of folic acid (696 mcg/day) were associated with a 31% lower risk for heart disease episodes, compared with lower folic acid intake levels (158 mcg/day). For vitamin B6, there was a 33% lower risk for heart disease episodes in subjects ingesting 4.6 mg/day, compared with subjects ingesting 1.1 mg/day. Individuals with high intakes of both folic acid and vitamin B6 experienced a 45% reduced risk for fatal and nonfatal heart attacks.
A major conclusion of this study is that intake of folic acid and vitamin B6 above the current recommended dietary allowance may be required to prevent heart disease. Each 100 mcg/day increase in folic acid was associated with a 5.8% lower risk of heart disease. It is estimated that 88%-90% of the population has dietary folic acid intakes below 400 mcg/day. Findings from the Health Professional Follow-up Study (involving male health practitioners) also demonstrated that high folic acid intake was associated with a significant reduction in heart disease risk. Thus, for both men and women, high levels of folic acid intake are strongly linked to the prevention of heart disease.
The current recommended dietary allowance for folic acid is 180 mcg/day for nonpregnant women. The average dietary intake in the United States among women is approximately 225 mcg/day. The overall evidence suggests that this level of intake is insufficient to minimize the risk of neural tube defects (e.g., spina bifida), and possibly heart disease. As such, many experts are urging that the recommended dietary allowance (RDA) be reset to the earlier level of 400 mcg/day.
Obtaining 400-700 mcg/day of folic acid is exceeding difficult to do without supplementation. The potential for this one simple intervention (a folic acid supplement) to prevent life-threatening problems is staggering, when you weigh all the evidence.
B Vitamins Help Preserve Memory and Cognitive Function
Deterioration of mental capacities has long been considered an aspect of the normal aging process. In recent years, however, the emerging scientific evidence has demonstrated that certain natural health products and supplements are effective in their ability to prevent, reverse, or even better manage cognitive impairment problems in older individuals. The Boston Veterans Affairs Normative Aging Study is one of many studies investigating the influence of nutrition on various aspects of age-related disorders.
In March of 1996, Drs. Riggs and associates published results from this study in The American Journal of Clinical Nutrition. Their findings indicated that older individuals with low blood concentrations of vitamin B12, vitamin B6, and the B vitamin folic acid had the poorest scores of brain function, measured by a battery of cognitive tests.
In previous studies, clinical deficiencies of B vitamins have been implicated in brain-related disorders, including reversible dementia (vitamin B12 and possibly folate), depression (folate), and electrophysiological dysfunction, including convulsions (vitamin B6). In healthy older adults, blood levels of B vitamins usually considered to be in the normal range were associated with poorer scores on tests of delayed recall, abstract reasoning, and selective attention. There is also good evidence that deficiencies of vitamin B12, folic acid, and vitamin B6 increase with age and are common in older adults. Thus, there is growing support for the premise that optimal B-vitamin status can prevent, slow or reverse the deterioration in memory and other mental capacities important to quality-of-life issues in older individuals.
The Normative Aging Study involved 70 male subjects, ages 54-81. The results of this study revealed that blood levels of vitamin B12 and folic acid appear to be related to cognitive performance in a different manner than vitamin B6 blood levels. Low blood levels of vitamin B12 and folic acid were associated with deficits in spatial copying. Higher blood levels of vitamin B6 were associated with better performance on two tests of memory. Another interesting finding was that nearly one half of the subjects in this study had low blood levels of vitamin B6 (<30 umol/L).
This study is extremely important because B vitamins are known to participate in brain chemistry and physiology. Vitamins B12 and folic acid are required as coenzymes in the synthesis of the neurotransmitters serotonin and catecholamines (adrenaline, norepinephrine). They are also required for the production of S-adenosylmethionine, which has known antidepressant properties. Vitamin B12 deficiency may also result in de-insulation of nerve fibers (demyelination), which produces a constellation of neurological symptoms. Vitamin B6 is a cofactor in the production of other neurotransmitters, including dopamine, norepinephrine, serotonin, GABA, and taurine.
Additionally, higher blood levels of homocysteine often result from subnormal intakes of folic acid, vitamin B12 and vitamin B6. High blood levels of homocysteine are associated with increased risk of cardiovascular, cerebrovascular (narrowed arteries in the brain), and peripheral vascular disease (narrowed blood vessels in the arms, hands, legs and feet).
Narrowed arteries in the brain (cerebrovascular disease) have been shown to be associated with decrements in psychomotor speed and on tests measuring fluid and visual abilities. Such cognitive dysfunction, therefore, may stem from high levels of homocysteine. As previously stated, vitamins B6, B12 and especially folic acid are key nutrients that prevent and reverse high blood levels of homocysteine.
In the Normative Aging Study, subjects with high levels of homocysteine performed, on average, like patients with mild Alzheimer's disease. They also exhibited difficulty in copying the most complex spatial figures. For example, few subjects in the highest 25 percent range of homocysteine concentrations completed the cube (22%) and tapered box (17%) correctly. By comparison, these figures are mastered by 50% of schoolchildren by age 13. Subjects with the lowest blood homocysteine levels demonstrated the best results on these tests.
The body of evidence continues to support the contention that B-vitamin nutritional status is crucial to the development and preservation of mental capacities throughout our lifetime. The sad reality is that many middle-age and elderly members of society have poor dietary intake and nutritional status of various B vitamins (vitamin B6, folic acid, etc.). For this reason, I continue to emphasize the multitude of benefits available from the daily use of a well-formulated multivitamin/mineral supplement that contains a B50 complex.
B-Vitamins and Cancer
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James Meschino, DC, MS
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