Godfrey P. Oakley

Association of Biochemical B12 Deficiency With Metformin Therapy and Vitamin B12 Supplements The National Health and Nutrition Examination Survey, 1999–2006

OBJECTIVE To describe the prevalence of biochemical B12 deficiency in adults with type 2 diabetes taking metformin compared with those not taking metformin and those without diabetes, and explore whether this relationship is modified by vitamin B12 supplements. RESEARCH DESIGN AND METHODS Analysis of data on U.S. adults ≥50 years of age with (n = 1,621) or without type 2 diabetes (n = 6,867) from the National Health and Nutrition Examination Survey (NHANES), 1999–2006. Type 2 diabetes was defined as clinical diagnosis after age 30 without initiation of insulin therapy within 1 year. Those with diabetes were classified according to their current metformin use. Biochemical B12 deficiency was defined as serum B12 concentrations ≤148 pmol/L and borderline deficiency was defined as >148 to ≤221 pmol/L. RESULTS Biochemical B12 deficiency was present in 5.8% of those with diabetes using metformin compared with 2.4% of those not using metformin (P = 0.0026) and 3.3% of those without diabetes (P = 0.0002). Among those with diabetes, metformin use was associated with biochemical B12 deficiency (adjusted odds ratio 2.92; 95% CI 1.26–6.78). Consumption of any supplement containing B12 was not associated with a reduction in the prevalence of biochemical B12 deficiency among those with diabetes, whereas consumption of any supplement containing B12 was associated with a two-thirds reduction among those without diabetes. CONCLUSIONS Metformin therapy is associated with a higher prevalence of biochemical B12 deficiency. The amount of B12 recommended by the Institute of Medicine (IOM) (2.4 μg/day) and the amount available in general multivitamins (6 μg) may not be enough to correct this deficiency among those with diabetes.OBJECTIVE To describe the prevalence of biochemical B(12) deficiency in adults with type 2 diabetes taking metformin compared with those not taking metformin and those without diabetes, and explore whether this relationship is modified by vitamin B(12) supplements. RESEARCH DESIGN AND METHODS Analysis of data on U.S. adults ≥50 years of age with (n = 1,621) or without type 2 diabetes (n = 6,867) from the National Health and Nutrition Examination Survey (NHANES), 1999-2006. Type 2 diabetes was defined as clinical diagnosis after age 30 without initiation of insulin therapy within 1 year. Those with diabetes were classified according to their current metformin use. Biochemical B(12) deficiency was defined as serum B(12) concentrations ≤148 pmol/L and borderline deficiency was defined as >148 to ≤221 pmol/L. RESULTS Biochemical B(12) deficiency was present in 5.8% of those with diabetes using metformin compared with 2.4% of those not using metformin (P = 0.0026) and 3.3% of those without diabetes (P = 0.0002). Among those with diabetes, metformin use was associated with biochemical B(12) deficiency (adjusted odds ratio 2.92; 95% CI 1.26-6.78). Consumption of any supplement containing B(12) was not associated with a reduction in the prevalence of biochemical B(12) deficiency among those with diabetes, whereas consumption of any supplement containing B(12) was associated with a two-thirds reduction among those without diabetes. CONCLUSIONS Metformin therapy is associated with a higher prevalence of biochemical B(12) deficiency. The amount of B(12) recommended by the Institute of Medicine (IOM) (2.4 μg/day) and the amount available in general multivitamins (6 μg) may not be enough to correct this deficiency among those with diabetes.

Update on Prevention of Folic Acid-Preventable Spina Bifida and Anencephaly

BACKGROUND The number of countries fortifying wheat and maize flour with folic acid has increased in the past 2 years. Folic acid prevents most cases of spina bifida and anencephaly by raising serum folate levels among women capable of bearing children, as does encouraging women to consume folic acid supplements prior to pregnancy. METHODS The progress in preventing these serious birth defects can be measured by tracking the number of countries now fortifying and program coverage in each. Country estimates of the number of pregnancies affected by spina bifida and anencephaly are calculated using a prefortification birth prevalence baseline and estimates of the proportion prevented by wheat and maize flour fortified with folic acid. RESULTS Current fortification programs are preventing about 22,000, or 9% of the estimated folic acid-preventable spina bifida and anencephaly cases. This represents an annual global decrease of about 6,600 folic acid-preventable spina bifida and anencephaly cases since 2006. CONCLUSIONS The pace of preventing these serious birth defects can be accelerated if more countries require fortification of both wheat and maize flour and if regulators set fortification levels high enough to increase a womans daily average consumption of folic acid to 400 mcg.

Utilization of prenatal genetic diagnosis in women 35 years of age and older in the United States, 1977 to 1978

As a measure of access to and acceptability of prenatal chromosomal diagnosis among older gravidas, we determined the ratio of use of prenatal diagnosis among women 35 years of age and older in Alabama, California, Manhattan, and Nebraska for the period 1977-1978. Utilization ratios were higher in 1978. Overall, utilization ratios were between 6% and 28%, well below the adjusted rates of 40% to 50% found in certain United States and British localities. Urban women tended to have higher utilization ratios than had rural women, and white women had higher ratios than had black women. Ratios were extremely low for black and rural residents. The oldest women (those greater than or equal to 40 years), who were at fivefold greater risk than women 35 to 36 years of age, had less than a onefold increase in utilization over the latter groups. The vast majority of older gravidas initiated prenatal care sufficiently early in their pregnancies to receive prenatal diagnosis. Current program strategies need to ensure access to prenatal diagnosis, especially for women greater than or equal to 40 years of age, women who are black, and women who live in rural areas.

Delaying folic acid fortification of flour : Governments that do not ensure fortification are committing public health malpractice

The failure of European governments to mandate universal fortification of flour with folic acid has allowed a continuing epidemic of preventable human illness. It is ironic that the United Kingdom has not required fortification, as it was a randomised controlled trial from the United Kingdom that conclusively proved that supplementation with synthetic folic acid prevents about 75% of spina bifida and anencephaly—common and serious birth defects.1 This study provided the primary scientific basis for the United States, Canada, Chile, and other countries to require fortification. In Europe fortification has been delayed because it has erroneously been portrayed as having definitive benefits for embryos and children and no benefits for adults, especially elderly people. Speculation of possible harm from fortification for elderly people, though hypothetical and not data driven, has resulted in unnecessary delay. Strong evidence exists that universal fortification benefits adults, including elderly people, and that it is safe. 2 3 Policy discussions should compare the definite …

Prenatal Chromosomal Diagnosis: Racial and Geographic Variation for Older Women in Georgia

In a study of Georgia women aged 40 years and older, 15% made use of prenatal chromosomal diagnosis. There was, however, substantial racial and geographic variation, ranging from a use ratio of 60% among whites in two large urban counties to 0.5% among blacks outside Augusta and Atlanta health districts. This simple population-based epidemiologic analysis suggests that future program planning for genetic services in Georgia should address ways to increase access by rural women, especially blacks. Similar analyses in other states could be used for planning genetic services.

Should folic acid fortification be mandatory? Yes

The UKs Food Standards Agency recently recommended mandatory folic acid fortification of some foods. Nicholas Wald and Godfrey Oakley argue that its a safe effective way of preventing spina bifida and anencephaly—but Richard Hubner and colleagues say that more research into the harms is needed

Maternal serum alpha-fetoprotein screening: a cost-benefit analysis.

The prenatal detection of fetal neural tube defects (NTD) is now possible by means of a multi-tiered program utilizing maternal serum alpha-fetoprotein (MSAFP) screening coupled with ultrasonography and amniocentesis where indicated. This paper considers the economic consequences of screening for fetal NTD a theoretical cohort of 100,000 pregnant women at risk of having an affected fetus who would elect to terminate their pregnancies if an affected fetus were found. The cost of the program was balanced against the benefits of the program, such as the averted costs of institutionalization, medical care, and the like. The total cost of the program to screen 100,000 such women was calculated to be

The Scientific Basis for Eliminating Folic Acid–Preventable Spina Bifida: A Modern Miracle from Epidemiology

2,047,780, or slightly over

2012 Update on global prevention of folic acid–preventable spina bifida and anencephaly

20 per woman screened, while the total economic benefits exceeded

Seizure disorder in mothers of children with orofacial clefts: A case-control study

4,000,000.