Prevalence of cobalamin deficiency in the Framingham elderly population

doi:10.1093/ajcn/60.1.2

The American Journal of Clinical Nutrition

Volume 60, Issue 1, July 1994, Pages 2-11

https://doi.org/10.1093/ajcn/60.1.2 Get rights and content

ABSTRACT

To determine whether the increased prevalence of low serum cobalamin concentrations in elderly people represents true deficiency, serum concentrations of cobalamin and folate and of metabolites that are sensitive indicators of cobalamin deficiency were measured in 548 surviving members of the original Framingham Study cohort. Serum cobalamin concentrations < 258 pmol/L were found in 222 subjects (40.5%) compared with 17.9% of younger control subjects (P < 0.001). Serum methylmalonic acid and total homocysteine concentrations were markedly elevated in association with cobalamin values < 258 pmol/L in 11.3% and 5.7%, respectively, of the cohort. Both metabolites were increased in 3.8% of the cohort, associated with significantly lower erythrocyte counts and higher mean cell volumes. Serum metabolites correlated best with serum cobalamin values, even when subnormal determinations were excluded. The prevalence of cobalamin deficiency was ≥ 12% in a large sample of free-living elderly Americans. Many elderly people with “normal” serum vitamin concentrations are metabolically deficient in cobalamin or folate.

References (79)

BrattstromL et al.
Higher total plasma homocysteine in vitamin B12 deficiency than in heterozygosity for homocystinuria due to cystathionine B-Synthase deficiency
Metabolism
(1988)
SavageDG et al.
Serum methylmalonic acid and total homocysteine in the diagnosis of deficiencies of cobalamin and folate
Am J Med
(1994)
KangSS et al.
Homocysteinemia due to folate deficiency
Metabolism
(1987)
AllenRH et al.
Elevation of 2- methylcitric acid I and II in the serum, urine and cerebrospinal fluid of patients with cobalamin deficiency
Metabolism
(1993)
MarcellPD et al.
Quantitation of methylmalonic acid and other dicarboxylic acids in normal serum and urine using capillary gas chromatography-mass spectrometry
Anal Biochem
(1985)
StablerSP et al.
Quantitation of total homocysteine, total cysteine and methionine in normal serum and urine using capillary gas chromatography-mass spectrometry
Anal Biochem
(1987)
GottliebC et al.
Rapid charcoal assay for intrinsic factor (IF), gastric juice unsaturated B-12 binding capacity, antibody to IF, and serum unsaturated B-12 binding capacity
Blood
(1965)
JoostenE et al.
Metabolic evidence that deficiencies of vitamin B-12 (cobalamin), folate and vitamin B- 6 occur commonly in the elderly
Am J Clin Nutr
(1993)
StablerSP et al.
Clinical spectrum and diagnosis of cobalamin deficiency
Blood
(1990)
IsraelssonB et al.
Homocysteine and myocardial infarction
Atherosclerosis
(1988)

NormanEC et al.

Screening elderly populations for cobalamin (Vitamin B12) deficiency using the urinary methylmalonic acid assay by gas chromatography mass spectrometry

Am J Med

(1993)

RosenbergIH et al.

Folate nutrition in the elderly

Am J Clin Nutr

(1982)

MuddSH et al.

Labile methyl balance for normal humans on various dietary regimens

Metabolism

(1975)

SuterPM et al.

Reversal of protein-bound vitamin B12 malabsorption with antibiotics in atrophic gastritis

Gastroenterology

(1991)

WilckenDEL et al.

Folic acid lowers elevated plasma homocysteine in chronic renal insufficiency: possible implications for prevention of vascular disease

Metabolism

(1988)

GaffneyGW et al.

Vitamin B12 serum concentrations in 528 apparently healthy human subjects of ages 12-94

J Gerontol

(1957)

CapeRD et al.

Serum vitamin B12 concentration in the elderly

Gerontol Clin

(1961)

KilpatrickGS et al.

The serum vitamin B12 concentration in the general population

Scand J Haematol

(1965)

WatersWE et al.

Serum vitamin B12 concentrations in the general population: a ten-year follow-up

Br J Haematol

(1971)

McLennanWJ et al.

Anaemia in the elderly

Q J Med

(1973)

SheridanDJ et al.

Blood indices, serum folate and vitamin B12 levels in the elderly

J Ir Coll Physicians Surg

(1974)

ElsborgL et al.

Serum vitamin B12 levels in the aged

Acta Med Scand

(1976)

BakerH et al.

Vitamin profiles in elderly persons living at home or in nursing homes, versus profile in healthy young subjects

J Am Geriatr Soc

(1979)

NormanEJ

Gas chromatography-mass spectrometry screening of urinary methylmalonic acid: early detection of vitamin B12 (cobalamin) deficiency to prevent permanent neurologic disability

GC- MS News

(1984)

BlundellEL et al.

Importance of low serum vitamin B12 and red cell folate concentrations in elderly hospital inpatients

J Clin Pathol

(1985)

HitzhusenJC et al.

Vitamin B12 levels and age

Am J Clin Pathol

(1986)

MarcusDL et al.

Low serum B12 levels in a hematologically normal elderly subpopulation

J Am Geriatr Soc

(1987)

BarberKE et al.

Vitamin B12 concentrations in the elderly: a regional study

N Z Med J

(1989)

HangerHC et al.

A community study of Vitamin B12 and folate levels in the elderly.

J Am Geriatr Soc

(1991)

Nilsson-EhleH et al.

Serum cobalamin in the elderly: a longitudinal study of a representative population sample from age 70 to 81

Eur J Haematol

(1991)

PennypackerLC et al.

High prevalence of cobalamin deficiency in elderly outpatients

J Am Geriatr Soc

(1992)

ElwoodPC et al.

Haemoglobin, vitamin B12 and folate levels in the elderly

Br J Haematol

(1971)

MagnusEM et al.

Folate and vitamin B12 (cobalamin) blood levels in elderly persons in geriatric homes

Scand J Haematol

(1982)

GarryPJ et al.

Folate and vitamin B12 status in a healthy elderly population

J Am Geriatr Soc

(1984)

LangdonFW

Nervous and mental manifestations of prepernicious anemia

JAMA

(1905)

LindenbaumJ et al.

Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis

N Engl J Med

(1988)

HealtonEB et al.

Neurologic aspects of cobalamin deficiency

Medicine

(1991)

StablerSP et al.

Elevation of total homocysteine in the serum of patients with cobalamin or folate deficiency detected by capillary gas chromatography-mass spectrometry

J Clin Invest

(1988)

ClarkeR et al.

Hyperhomocysteinemia: an independent risk factor for vascular disease

N Engl J Med

(1991)

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Prevalence of cobalamin deficiency in the Framingham elderly population

ABSTRACT

Metabolism

Am J Med

Metabolism

Metabolism

Anal Biochem

Anal Biochem

Blood

Am J Clin Nutr

Blood

Atherosclerosis

Am J Med

Am J Clin Nutr

Metabolism

Gastroenterology

Metabolism

Vitamin B12 serum concentrations in 528 apparently healthy human subjects of ages 12-94

J Gerontol

Serum vitamin B12 concentration in the elderly

Gerontol Clin

The serum vitamin B12 concentration in the general population

Scand J Haematol

Serum vitamin B12 concentrations in the general population: a ten-year follow-up

Br J Haematol

Anaemia in the elderly

Q J Med

Blood indices, serum folate and vitamin B12 levels in the elderly

J Ir Coll Physicians Surg

Serum vitamin B12 levels in the aged

Acta Med Scand

Vitamin profiles in elderly persons living at home or in nursing homes, versus profile in healthy young subjects

J Am Geriatr Soc

Gas chromatography-mass spectrometry screening of urinary methylmalonic acid: early detection of vitamin B12 (cobalamin) deficiency to prevent permanent neurologic disability

GC- MS News

Importance of low serum vitamin B12 and red cell folate concentrations in elderly hospital inpatients

J Clin Pathol

Vitamin B12 levels and age

Am J Clin Pathol

Low serum B12 levels in a hematologically normal elderly subpopulation

J Am Geriatr Soc

Vitamin B12 concentrations in the elderly: a regional study

N Z Med J

A community study of Vitamin B12 and folate levels in the elderly.

J Am Geriatr Soc

Serum cobalamin in the elderly: a longitudinal study of a representative population sample from age 70 to 81

Eur J Haematol

High prevalence of cobalamin deficiency in elderly outpatients

J Am Geriatr Soc

Haemoglobin, vitamin B12 and folate levels in the elderly

Br J Haematol

Folate and vitamin B12 (cobalamin) blood levels in elderly persons in geriatric homes

Scand J Haematol

Folate and vitamin B12 status in a healthy elderly population

J Am Geriatr Soc

Nervous and mental manifestations of prepernicious anemia

JAMA

Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis

N Engl J Med

Neurologic aspects of cobalamin deficiency

Medicine

Elevation of total homocysteine in the serum of patients with cobalamin or folate deficiency detected by capillary gas chromatography-mass spectrometry

J Clin Invest

Hyperhomocysteinemia: an independent risk factor for vascular disease

N Engl J Med