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Tripathy et al Int. J. Pure App. Biosci. 5 (6): 208-214 (2017) ISSN: 2320 – 7051
DOI: ISSN: 2320 – 7051
Int. J. Pure App. Biosci. 5 (6): 208-214 (2017)
Review Article

Interrelationship of Micronutrients: Antagonism and Synergism

Tripathy S.1, Dhaduk J. J.2 and Kapadiya S.3

Research Scholar, 2Professor, 3Senior Research Assistant
Department of Food Science and Nutrition,
ASPEE College of Home Science and Nutrition
Sardarkrushinagar Dantiwada Agricultural University, Sardarkrushinagar-385506
*Corresponding Author E-mail:
Received: 5.10.2017 | Revised: 13.11.2017 | Accepted: 16.11.2017

Vitamins and minerals are considered as micronutrients for body but they play vital role in
different body functions. These minerals and vitamins interact with each other’s either
synergistically to increase each other’s activity or antagonistically to decrease their effectiveness
in body. Major vitamin antagonisms include antagonism between vitamin A and D, vitamin C
and vitamin K, vitamin K and some antibiotics, vitamin C and vitamin B12, Fe, Co etc. Some of
the important synergism between micronutrients includes thiamine, riboflavin, pantothenic acid,
vitamin D, B12, E. So during diet formulation these factors should be taken care to avoid any
Key words: Antagonism, mineral, synergism, vitamin

INTRODUCTION nutrients like proteins; fats and carbohydrates.

In human body system, every nutrient has a Vitamins also have synergistic and
specific role either directly on the body or antagonistic relationships. Vitamins are
through interfering with the function of other involved in several body functions such as
nutrients. These interrelationships among they act as coenzymes and are involved
different nutrients either may be advantageous synergistically in many enzymatic reactions.
or may lead to deficiency of each other. A loss They can also protect against deficiencies of
of this vital balance, particularly among other vitamins.
different trace vitamins may lead to subclinical Vitamin Antagonisms
deficiencies or decreased bioavailability An anti-vitamin is a substance which makes
leading to different deficiency diseases. the vitamin unavailable or ineffective within
Chemically vitamins are amines which the body. Specifically these substances block
are very much essential for maintenance of the action of some vitamins. Sometimes, the
vital body function. They are present in small antagonism may not be direct but indirectly
amounts in food. They are involved in the they may increase the requirements of target
absorption and utilization of the major vitamins because of their excessive intake.

Cite this article: Tripathy, S., Dhaduk, J.J. and Kapadiya, S., Interrelationship of Micronutrients:
Antagonism and Synergism, Int. J. Pure App. Biosci. 5(6): 208-214 (2017). doi:

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Tripathy et al Int. J. Pure App. Biosci. 5 (6): 208-214 (2017) ISSN: 2320 – 7051
Vitamin A and D are mutually antagonistic to Vitamin C and vitamin E interactions
each other. Vitamin A reduces the toxic effects Vitamin C and vitamin E are both antioxidants
of vitamin D9. Vitamin A enhances the and protect against reactive oxygen species.
absorption or retention potassium and These substances are of parallel interest as
phosphorus. It has been reported that vitamin water-soluble vitamin C regenerates lipid
B1 can have an antagonistic action against soluble vitamin E in an outside the cell of the
vitamin B121. The antagonistic relationship organism36. There is much evidence indicating
between vitamin C and vitamin B12 is an that vitamins C and vitamin E may also have a
indirect one. Vitamin C neither directly affects physiologically relevant interaction.
B12, nor destroys this vitamin. Vitamin C In guinea pigs, vitamin C deficiency
enhances iron absorption. Increased amount of led to reduced levels of vitamin E2 and
iron in body leads to deficiency of cobalt, administration of oxidized frying oil, large
which is an integral part of vitamin B1226. This doses of vitamin C increased the level of
is however a rare occurrence and may affect vitamin E in the liver, kidney, spleen, and
only a small segment of the population who lungs17. In inherently scorbutic rats, vitamin C
may suffer from iron overload disorders37. deficiency led to reduced vitamin E levels in
Vitamin A antagonists the liver, kidney, and heart. In normal rats,
Blood-thinning medications and other drugs, vitamin C supplementation increased plasma
including aspirin, phenobarbital, arsenicals and vitamin E level8. Contradicting to this Hruba et
dicumarol (a drug used medically to retard al.14 reported that vitamin C deficiency did not
blood clotting) destroy vitamin A in the body. affect the plasma vitamin E level in guinea
Vitamin A is also depleted when nitrosamines pigs. The excessive doses of vitamin C may
are formed in the stomach from the union of reduce plasma vitamin E levels8.
nitrites with secondary amines and when the The estrogen in oral contraceptives is
mucous membranes of our respiratory also an antagonist of vitamin E. Vitamin C
passages are exposed to air pollutants such as reacts with several alien substances in the
carbon monoxide, ozone, sulphur dioxide, bloodstream. All drugs and pollutants can be
nitrogen dioxide, lead, hydrocarbons, etc. considered as vitamin C antagonists. Some of
Vitamin K antagonists the foremost vitamin C antagonists include
The amount of vitamin K needed by humans is ammonium chloride, stribesterol, thiouracil,
very small and a deficiency is highly unlikely atropine, barbiturates and antihistamines. All
because this vitamin is in a wide variety of stresses (surgery, emotional outbursts and
commonly available plant foods and again it is upsets, acute pressures, extremes of heat and
synthesized by bacteria in the intestinal tract. cold and all drugs) as well as alcoholic
However, antibiotic therapy (penicillin, beverages are vitamin C antagonists.
streptomycin, tetracycline, chloromycin, Anemia is often observed in vitamin C
terramycin, etc) suppresses bacterial growth deficient patients. A normocytic or macrocytic
and consequently, the synthesis of vitamin K. anemia is generally observed, though
Other vitamin K antagonists include the drugs megaloblastic has been reported sometimes in
dicumarol and hydrocoumarol, which are used same patients. The presence of megaloblastic
by medical people to relieve thrombosis anemia in some scorbutic patients has given
(abnormal formation of blood clots in the rise to the consideration that either a dietary
blood vessels). As the chemical structure of deficiency of folic acid existed or that folate
these antihistamines is similar to that of metabolism was impaired in vitamin C
vitamin K, they act as anticoagulants by deficiency. In some instances the
interfering with the synthesis of pro-thrombin megaloblastic anemia was effectively treated
and the other natural clotting factors. Large with ascorbic acid alone, while in other
doses of vitamin A can also inhibit the reports, additional amounts of folic acid
absorption of vitamin K. supplementation were required31.
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Vitamin E supports a healthy immune system The urinary excretion of 4-pyridoxic acid (the
and may help to protect against cardiovascular major metabolite of vitamin B6) was elevated
disease by decreasing atherosclerosis and with an increased intake of ascorbic acid31.
helping the blood circulation. Because of these The most potent folacin (folic acid) antagonist
effects on the blood, taking vitamin E is aminopterin, a substance that has been used
supplements may increase the risk of bleeding, in the medical treatment of leukemia, a disease
especially in patients taking anticoagulant in which there is a marked increase in the
medications such as warfarin or patients of production of leucocytes (white blood cells).
vitamin K deficiency25. Some research indicates that large doses of
Vitamin K is necessary for blood to vitamin C block the absorption of vitamin
coagulate effectively. Patients with a vitamin B1231.
K deficiency have an increased risk of Vitamin Synergisms
uncontrolled bleeding. There are some Synergy is defined as the combined interaction
postulations which suggest that vitamin E of several system elements which produces an
inhibit the vitamin K dependent carboboxylase entirely different or greater effect compared to
activity and subsequently inhibit the what they produce by their separate effects. In
many cases, a synergistic relationship between
coagulation cascade32. Therefore, high amount
certain elements can produce long-term
of vitamin E decrease the activity of vitamin K
in coagulation. α-tocopheryl hydroquinone is
Vitamins are involved in many reactions and
an oxidized product of α- tocopherol and an
also have beneficial effect or synergistic
efficient antioxidant. Vitamin E quinine is a
effect. They act as coenzymes and are
potent anticoagulant as inhibitor of vitamin K
involved synergistically in many enzymatic
dependent carboxylase that controls blood
reactions. They can also protect against
deficiencies of other vitamins.
B vitamin Antagonists Table: 1 Different vitamin and their synergistic
Cortisone is an antagonist of vitamin B6 vitamins35
(pyridoxine). Since the body needs B vitamins Vitamins Synergist Vitamins
to metabolize sugars, B vitamins are depleted A B2-C-E-B3-B1-B6
D B12-E
when refined sugar or flour is consumed as E A-B6-C-B12-B1-B5-B3-D
refined sugar and flour are devoid of B B1 E-C-B6-B12-B3-B5-A-B2
B2 A-B3-B10
vitamins that existed in the beet, cane or grain
B6 E-A-B6-B3-B5
before refining. Specifically, the body’s supply B12 B1-B3-B6-E-B5-C--D
of vitamin B1, vitamin B2, biotin, choline, C A-E-B6-B3-B5
niacin and the mineral magnesium are depleted B3 B1-B2-B6-A-B5-E
B5 C-E-A-B1-B3-B6
when refined sugar and flour are consumed.
Alcoholic beverages are antagonists of thiamin
Antioxidant vitamin supplementations may
and the other B-complex vitamins. Coffee is
reduce the severity of trypanosome infection
another popular beverage that is a B vitamin by offering protection against possible
antagonist, because it contains caffeine and oxidative injuries associated with the disease33
other noxious substances like chlorogenic acid. and thus, beneficial in pregnancy related
Inositol deficiency may occur among coffee infections (malaria) and complication
drinkers along with deficiency of biotin and (hyperlipidemia). In the last 20 years, some
thiamin. Raw fish and raw shellfish, including clinical and epidemiological researches have
oysters, are also B-complex antagonists as raw suggested a potential protective effect of
fish contains the enzyme thiaminase which antioxidant nutrients such as beta-carotene,
destroys thiamine. This is one of many reasons vitamin C, and vitamin E on the risk of cancer
not to eat the Japanese dish, sashimi (raw fish) and cardiovascular diseases. Vitamin C can
or any other raw seafood. also regenerate oxidized Vitamin E by
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reducing it back to its active form. The key an increased risk for heart disease31. Thiamine
step is the reaction between the tocopheroxyl deficiency is often accompanied by
radical and vitamin C5. Vitamin C regenerates disturbance of riboflavin metabolism, causing
active vitamin E and increases cholesterol considerable excretion of riboflavin in urine.
excretion3. Plasma tocopherol levels also In another interaction, deficiency of
improved upon supplementation of vitamins E pantothenic acid affects adversely the
and C, this improvement suggests synergism mobilization of riboflavin from the liver.
of vitamin C with glutathione peroxides to Administration of pantothenic acid of deficient
revitalize vitamin E19. animals increases the mobilization of
Vitamin K2 (menaquinone) is riboflavin from liver and raises the levels of
responsible for activating certain proteins by riboflavin in blood31.
adding CO2 (carbon dioxide) to them. The liver of rats fed on thiamine
Vitamins A and D help body to absorb zinc deficient or riboflavin deficient diets contained
which in turn enables body to absorb fat- smaller amount of niacin than normal
soluble vitamins. Vitamins A, D, and K2 work controls31. Treatment of pellagra with niacin
together to build strong bones and teeth, precipitates symptoms of thiamine and
promote growth, protect against calcification riboflavin deficiencies indicating that niacin
of the soft tissues, and support immune deficiency is accompanied by secondary
system20. deficiency of thiamine and riboflavin.
Vitamin B synergism Baker et al.24 followed whole blood
Vitamin B12 supports the formation of healthy ascorbic acid levels in normal adult men
red blood cells. Taking folic acid (vitamin B9) subjected to depletion and repletion of vitamin
can mask the effects of megaloblastic anemia. B6. Whole blood level of ascorbic acid
The interaction between folic acid and vitamin progressively fell during the vitamin B6
B12 can increase the effects of the anemia and depletion phase and returned to normal level
lead to permanent neurological damage. upon repletion with pyridoxine. In a
For the conversion of folic to folinic acid, subsequent study on Vitamin C deficiency in
vitamin B12 is essential. Folic acid therapy of adult men, the urinary excretion of free
patients, suffering from sprue, causes an pyridoxine was measured31.
increase in plasma vitamin B12 content. Vitamin B6 deficiency has been reported to
Vitamin B12 deficiency causes a rise in cause impairment in vitamin B12 absorption in
unconjugated folates and depletion of the rat, resulting in a lowering of vitamin B12
intracellular conjugated folates. levels in the serum and in reduced vitamin B12
Vitamin B6, a member of the B family stores in the liver31. The riboflavin deficiency
of vitamins along with B12, promotes the in the rat slowed the uptake of labeled
production of hormones and neurotransmitters, pyridoxine into the liver and decreased the
the chemicals that carry signals between the conversion of pyridoxine to its metabolites31.
nerves. Vitamin B6 is also important for the Interaction among vitamin C, vitamin E,
production of healthy red blood cells because and β-carotene
the presence of B6 enhances the absorption of The effects of vitamin C (ascorbic acid),
B1231. vitamin E (α-tocopherol), and β-carotene as
Administration of thiamine, riboflavin antioxidants and their cooperative action
and pantothenic acid offered partial protection against the oxidation of lipid in solution,
from spontaneous seizures, which may be due membranes, and lipoproteins have been
to vitamin B6 deficiency31. A deficiency in studied and reviewed by Niki and associates.
vitamin B6 can lead to a deficiency in B12. In Ascorbic acid and α -tocopherol act as potent
addition, vitamins B6, B12 and folic acid all and probably the most important, hydrophilic
work together to control the level of and lipophilic antioxidants, respectively. They
homocysteine, an amino acid associated with function at their own site individually and
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furthermore act synergistically. β-carotene acts but the same report was not replicated during
as a weak antioxidant in solution and has further study by Newmark et al.22. Again
lower reactivity toward radicals than that of α Herbert et al.13 reported that some patients
– tocopherol23. having spinal cord injury found to have
Some other interrelationship of vitamins: deficient amount of vitamin B12 after receiving
Biotin and pantothenic acid: Biotin ascorbic acid for a period of 2 years. Lucock et
deficiency may be aggravated by a al.18 reported that dietary vitamin C regulates
simultaneous pantothenic acid deficiency. The red cell folate status of body either directly or
addition of biotin to the diet not only protects indirectly protecting dietary 5-methyle-tetra
the animals from biotin deficiency but also hydro folate as vitamin C is an antioxidant. So
reduces the severity of the symptoms of it can be said that antioxidant vitamin C is
pantothenic acid deficiency31. critical in sparing highly labile trace levels of
Vitamin A, E and K: It has been shown that the natural 5-methyle- tetra hydro folate.
albino rats fed on a vitamin K deficient diet
develop signs of vitamin K deficiency when CONCLUSION
vitamin A in diet is increased. Considerable In human daily requirements of vitamins and
amount of work has been carried out by minerals and very less and also considered as
different workers on the role of vitamin E in micronutrients. The understanding of nutrition
influencing storage and mobilization of and its important role in health is most
vitamin A in liver. Administration of vitamin important and intricate part of health care,
E helps to increase the storage of vitamin A in particularly among today's progressive health
liver31. care providers. Vitamin interrelationship with
Ascorbic acid and other vitamins: The other nutrients and drugs are very important
albino rat can synthesize ascorbic acid. This study for the nutrition science personnel to
synthetic capacity, however, is diminished avoid unnecessary side effect of both
considerably in thiamin and riboflavin deficiency and toxicity of micronutrients.
deficiencies. This indicates that both these Vitamin synergism action is very useful for the
vitamins play an important role in the body proper mechanism action and also
biosynthesis of ascorbic acid. A depletion of effective for other nutrients absorption in the
the ascorbic acid content of tissues of rats body. Nutritional therapeutics has largely
occurred when the animals were fed on diets been directed towards the recognition and
deficient in vitamin A or thiamin or correction of nutritional deficiencies. It is now
riboflavin31. becoming evident that a loss of homeostatic
Folic acid and Vitamin B12: For the equilibrium between the nutrients can also
conversion of folic to folinic acid, vitamin B12 have an adverse effect upon health. A loss of
is essential. Folic acid therapy of patients, this vital balance, particularly between the
suffering from sprue, causes an increase in trace elements, can lead to subclinical
plasma vitamin B12 content. Vitamin B12 deficiencies.
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