Jashore University of Science and Technology

Department of Nutrition & Food Technology

An assignment on Megaloblastic macrocytic anemia

Course Title: Advanced Nutrition 2

Course No: NFT-5201

Submitted To Submitted by

Dr Md. Shimul Isla Roll no: MS-210931

Associate Professor Course no: NFT-5201
Dept. of Nutrition & Food Dept. of Nutrition &
Technology Food Technology
Jashore University of Jashore University of
Science & Technology Science & Technology.
 Deficiency: Megaloblastic macrocytic anemia

Deficiency of vitamin B12, like that of folate, results in megaloblastic macrocytic anemia.
Manifestations of vitamin B12 deficiency occur in stages. Initially, serum vitamin B12
concentrations diminish; serum B12 concentrations, however, may remain normal until stores of
the vitamin become depleted. Second, cell concentrations of the vitamin diminish. Third, DNA
synthesis decreases and serum homocysteine and methylmalonic acid concentrations increase.
Finally, morphological and functional changes occur in blood cells and precursor blood cells in
bone marrow resulting in macrocytic megaloblastic (large immature cell) anemia [1]. Most
deficiency signs and symptoms are of neurologic and hematologic origin; some signs and
symptoms include skin pallor, fatigue, shortness of breath, palpitations, insomnia, tingling and
numbness (paresthesia) in extremities, abnormal gait, loss of concentration, memory loss,
disorientation, swelling of myelinated fibres, and possibly dementia. Neurological problems
occur in about 75% to 90% of deficient people [2,3]. The megaloblastic macrocytic anemia
associated with a vitamin B12 deficiency is detailed under both “Folate” and “Vitamin B12
(Cobalamin),” because deficiencies of both results in megaloblastic macrocytic anemia.
Megaloblastic anemia related to vitamin deficiency can be corrected with large doses of folate.
However, the neuropathy, characterised by demyelination of nerves, caused by a lack of vitamin
B12 is not responsive to folate therapy. The neuropathy is usually found in vitamin B12–
deficient people with decreased activity of both vitamin B12–dependent enzymes. Its cause may
be related to the availability of methionine [4,5]. The neuropathy can be facilitated through
increased exogenous methionine or an accelerated production of methionine from homocysteine,
a reaction that requires vitamin B12.
An inadequate amount of methionine caused by a deficiency of vitamin B12 decreases the
availability of S-adenosyl methionine (SAM). Remember that SAM is required for methylation
reactions, essential to myelin maintenance and thus neural function. SAM deficiency in the
nervous system (i.e., cerebrospinal fluid) has been implicated in the pathogenesis of cobalamin
neuropathy [6]. In addition to anemia, plasma vitamin B12 concentrations are inversely
associated with plasma homocysteine concentrations [7-12]. Elevated plasma homocysteine
concentrations are considered a risk factor for coronary heart disease, and concentrations may be
lowered with vitamin B12, folate, and vitamin B6 supplements [7, 10-13]. This relationship
among vitamin B12, folate, vitamin B6, plasma homocysteine concentrations, and heart disease
is discussed in further detail in this chapter's “Folate” section. Inadequate absorption of the
vitamin, rather than inadequate dietary intake, causes most of the vitamin B12 deficiency seen in
the United States. However, a strict vegetarian diet can quickly produce a deficiency of the
vitamin in infants or young children with minimal stores of the vitamin. In contrast to children,
adults consuming animal-based diets who switch to strict vegetarian diets without consuming
vitamin-fortified foods may not develop clinical symptoms of deficiency for decades, because
they have accumulated fairly large vitamin stores. Inadequate vitamin B12 absorption can result
from several problems and is especially prevalent in older people.
Malabsorption can result from pernicious anemia, an autoimmune condition in which the body
produces antibodies that attack gastric parietal cells [14], thereby diminishing IF production.
Remember, IF is required to absorb the vitamin. Other conditions that can impair the absorption
of the vitamin include those causing a lack of IF, such as atrophic gastritis (loss and
inflammation of gastric cells) or gastrectomy (removal of all or a portion of the stomach). In
some forms of atrophic gastritis, antibodies are made against the proton pump in gastric parietal
cells. Diminished hydrochloric acid release (achlorhydria) also decreases the release of the
vitamin bound to food, causing malabsorption of the vitamin. People with a decreased absorptive
surface in the ileum, such as occurs with ileal resection, celiac and tropical sprue, ileitis
(inflammation of the ileum) also malabsorb the vitamin and are at risk for deficiency. People
with Zollinger-Ellison syndrome produce excessive quantities of gastric acid, which results in
increased acid release both into the stomach and passed into the small intestine with the chyme.
The increased acid in the small intestine lowers the intestinal pH and is thought to impair the
release of B12 from the R-protein and the binding of the vitamin to IF. In addition, people with
parasitic infections such as tapeworms may develop a vitamin B12 deficiency because the
parasite uses the vitamin, and consequently, its availability to the infected person is limited.
Prolonged use of some medications, such as H2 blockers and proton pump inhibitors used to
treat people with ulcers or gastroesophageal reflux disease (GERD), also is associated with
diminished absorption of vitamin B12. Bacterial overgrowth occurs because of the higher
intestinal pH (less acid is produced, because of the medications), and the bacteria use the vitamin
B12 and thus limit its availability. Finally, people who have poor vitamin B12 status may exhibit
deterioration of nervous system function, especially demyelinating problems, following nitrous
oxide anesthesia [15-17]. Nitrous oxide (an anesthetic agent) has been shown to inhibit the
activity of methionine synthase by reacting with methylcobalamin and possibly altering the
oxidation state of the cobalt (from 1+ to 3+). The incidence of vitamin B12 deficiency in the
elderly may be as high as 15%, and the vitamin B12 content of multivitamin preparations is
usually not sufficient for treatment. Oral vitamin B12 in amounts of at least 6 to 9 μg and
possibly up to 300 μg appears necessary to correct deficiency in the elderly [18]. Treating
pernicious anemia or deficiency secondary to malabsorption often requires monthly
intramuscular injection of the vitamin in amounts of 500 to 1,000 μg or oral ingestion of
pharmacologic amounts (2 mg) of the vitamin. Vitamin B12 nasal sprays also are available.
Nascobal ®, for example, provides the vitamin as cyanocobalamin (500 μg/spray) in a nasal
spray that is beneficial to people with malabsorptive disorders such as inflammatory bowel
disease or those with pernicious anemia.

Reference:
1. Herbert V. Staging of vitamin B12 (cobalamin) status in vegetarians. Am J Clin Nutr
1994; 59(suppl):1213S–22S.
2. Food and Nutrition Board. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin,
Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington,
DC: National Academy Press, 1998, pp. 306–56.
3. Beck W. Neuropsychiatric consequences of cobalamin deficiency. Adv Intern Med 1991;
36:33–56.
4. Metz J. Pathogenesis of cobalamin neuropathy: Deficiency of nervous system S-
adenosylmethionine. Nutr Rev 1993
5. Davis R. Clinical chemistry of vitamin B12. Adv Clin Chem 1984; 24:163–216.
6. Council on Scientific Affairs, American Medical Association. Vitamin preparations as
dietary supplements and as therapeutic agents. JAMA 1987; 257:1929–36.
7. Pancharuniti N, Lewis C, Sauberlich H, Perkins L, Go R, Alvarez J, Masaluso M, Acton
R, Copeland R, Cousins A, Gore T, Cornwell P, Roseman J. Plasma homocysteine,
folate, and vitamin B12 concentrations and risk for early-onset coronary artery disease.
Am J Clin Nutr 1994; 59:940–48.
8. Mansoor M, Ueland P, Svardal A. Redox status and protein binding of plasma
homocysteine and other aminothiols in patients with hyperhomocysteinemia due to
cobalamin deficiency. Am J Clin Nutr 1994; 59:631–35.
9. Ubbink J. Vitamin B12, vitamin B6, and folate nutritional status in men with
hyperhomocysteinemia. Am J Clin Nutr 1993; 57:47–53
10. Shimakawa T, Nieto F, Malinow M, Chambers L, Schreiner P, Szklo M. Vitamin intake:
Possible determinant of plasma homocysteine among middle-aged adults. Ann Epidemiol
1997; 7:285–93.
11. Shimakawa T, Nieto F, Malinow M, Chambers L, Schreiner P, Szklo M. Vitamin intake:
Possible determinant of plasma homocysteine among middle-aged adults. Ann Epidemiol
1997; 7:285–93.
12. Ubbink J, Vermaak W, Merwe A, Becker P, Delport A, Potgieter H. Vitamin
requirements for treating hyperhomocysteinemia in humans. J Nutr 1994; 124:1927–33.
13. Refsum H, Ueland P, Nygard O, Vollset SE. Homocysteine and cardiovascular disease.
Ann Rev Med 1998; 49:31–62.
14. Ban-Hock T, van Driel I, Gleeson P. Pernicious anemia. Engl J Med 1997; 337:1441–48.
15. Metz J. Cobalamin deficiency and the pathogenesis of nervous system disease. Ann Rev
Nutr 1992; 12:59–79.
16. Flippo T, Holder W. Neurologic degeneration associated with nitrous oxide anesthesia in
patients with vitamin B12 deficiency. Archives Surg 1993; 128:1391–95.
17. Guttormsen A, Refsum H, Ueland P. The interaction between nitrous oxide and
cobalamin biochemical effects and clinical consequences. Acta Anaesthesiol Scand 1994;
38:753–56.
18. ler S, Lindenbaum J, Allen R. Vitamin B12 deficiency in the elderly: Current dilemmas.
Am J Clin Nutr 1997; 66:741–49.