Anemias can be characterized when there is a reduction in the concentration of red blood cells or inability to maintain adequate blood oxygen levels. This is mainly due to poor diet or dysfunction in the absorption of nutrients.
When the reserves of certain nutrients, such as iron or vitamins , have been depleted in the body and food or digestion is not able to replace nutrients, physiological and symptomatic manifestations may appear.
The time for the condition to manifest can be quite variable, depending on dietary factors and the body’s ability to digest and absorb nutrients.
Nutritional follow-up research indicates that, on average, it is possible that after ceasing the intake or absorption of nutrients, the body can maintain adequate levels of vitamin B12 for up to 5 years, while the organic reserves of folates ( folic acid or vitamin B9) remain for only 4 months.
Therefore, the presentation of symptoms can be quite time-consuming and, at times, not even occur, if the blood changes were small.
- 1 What is pernicious anemia?
- 2 After all, what is an intrinsic factor?
- 3 The role of vitamin B12
- 4 Red blood cells
- 5 Megaloblastic and pernicious anemia
- 6 Causes
- 7 Associated conditions
- 8 Groups of risk
- 9 Symptoms
- 10 Diagnosis
- 11 Exams
- 12 Is there a cure?
- 13 Treatment
- 14 Medicines
- 15 Living together
- 16 Prognosis
- 17 Complications
- 18 How to prevent
The anemia , pernicious is a type of autoimmune disorder in which there is a reduction or inhibition of intrinsic factor, responsible for the synthesis of vitamin B12 in the intestine.
Pernicious anemia is mainly caused by atrophy of the stomach wall or other disorders that prevent the correct production of the glycoprotein called intrinsic factor.
In healthy individuals, the substance produced in the stomach is essential for vitamin B12 to be properly absorbed in the small intestine.
Despite being associated with possible gastric changes, pernicious anemia does not always present symptoms, which can make diagnosis difficult.
The most recurrent signs can involve weakness, indisposition, headaches and disturbed memory and concentration.
In most cases, pernicious anemia is associated with autoimmune action, in which the body itself destroys the stomach cells responsible for the production of the intrinsic factor. In this case, some experts refer to the dysfunction as true pernicious anemia .
But it can also be caused by prolonged use of medications, such as antacids (which cause the intrinsic factor to be inhibited) or after stomach surgery, such as bariatric ones.
With incorrect or deficient absorption of B12, there are changes in the production of red blood cells, also called red blood cells, in the blood. The result is that the blood cells cannot form properly, so they are larger than normal.
In addition, there is a weakening of red blood cells, causing them to be eliminated more quickly and resulting in a decrease in their blood concentration. These changes in the structure of red blood cells constitute megaloblastic anemia .
But it is necessary to differentiate between anemias caused by poor diet and those caused by autoimmune diseases or secondary conditions.
In the case of pernicious, the condition is quite confused with other anemias that cause vitamin B12 deficiency , which are also megaloblastic (cause changes in the size of red blood cells).
Treatment consists of supplementing vitamin B12 and monitoring symptoms, which tends to show significant improvements in short periods of time.
The disease is listed under the ICD-10 in code D51.0 – Anemia due to vitamin B12 deficiency due to intrinsic factor deficiency.
The intrinsic factor is a protein produced in the stomach. It has a facilitating action due to the aid in transporting B12 from the stomach to the intestine, where the vitamin will be sent to the blood.
Synthetically, the protein initially acts by binding to vitamin B12, making the B12 molecule protected from gastrointestinal secretions and preventing them from being digested.
Then the intrinsic factor binds to specific receptors that are concentrated in the ileum mucosa (the final part of the small intestine). Then B12 will be transported into the bloodstream.
Thus, with the lack of the intrinsic factor, B12 may even reach the intestine, but it will be lost by non-absorption.
When the intrinsic factor is absent, on average, only 1/50 of the vitamin B12 ingested is absorbed by the intestine. This is an extremely low amount.
As the vitamin acts directly on the maturation of red blood cells, when the stocks of B12 decrease, the body produces large red blood cells (macrocytes), which have very delicate and fragile membranes, in addition to reducing cell proliferation.
The result is that the blood has lower concentrations of red blood cells than normal.
Vitamin B12 makes up the vitamin B complex. There are 8 water-soluble substances (which dissolve in water): vitamin B1 (thiamine), B2 (riboflavin), B3 (niacin), B5 (pantothenic acid), B6 (pyridoxine), B7 ( biotin ), B9 (folic acid) and B12 (cobalamin).
As the components of this B complex act on cellular metabolism and, therefore, perform several organic functions, the lack or alteration of normal levels can lead to neurological, dermatological and gastrointestinal diseases.
Specifically regarding vitamin B12, its action occurs in the correct formation and maintenance of cell life. The substance is synthesized exclusively by microorganisms, that is, animals and plants are not able to produce it.
Concentrated mainly on animal tissues, the main sources of human ingestion are through meat, milk and eggs.
In healthy individuals, the intestinal flora synthesizes approximately 5mcg per day of vitamin B12. When a meal of animal origin (milk, eggs or meat) begins, processing of the vitamin begins in the mouth and extends to the small intestine.
For the correct absorption of the substance, the action of the carrier molecule (intrinsic factor) is necessary.
It is only in the small intestine that vitamin B12 binds to the intrinsic factor and is sent to the cells of the intestinal mucosa to be absorbed.
Therefore, the deficiency or inability of the intrinsic factor to act can cause vitamin B12 malabsorption, leading to pernicious anemia.
Where does the vitamin act?
- Red blood cells : vitamin B12 acts in the formation of red blood cells, being essential to maintain the correct functioning of red blood cells;
- Central nervous system : B12 promotes the maintenance of myelin, a layer that protects the nerves. Without the vitamin, there is a wear of the substance called demyelination, which affects the functions of the central and peripheral nervous system;
- Action on DNA : there are studies that point to the action of B12 in DNA cells, avoiding risks to the integrity of chromosomes. In summary, B12 deficiency may be associated with the risks of developing cancer.
What can affect vitamin B12 levels?
Vitamin B12 deficiency can have several causes, such as insufficient intake, gastric disorders, inefficient or insufficient absorption, in addition to the action of medications, such as antacids.
People who are nutritionally poor and vegetarians may experience reduced vitamin B12 levels.
Other factors, such as diseases that affect intestinal functions and reduce the absorption of nutrients, can decrease synthesis.
B12 deficiency is diagnosed taking into account the serum levels of the substance.
The ideal amount is still widely debated among scholars, as well as its impacts on the organism. But, on average, it is estimated that the appropriate levels are around:
- Severe deficiency: less than 150pg / mL;
- Deficiency: between 150pg / mL and 200 pmol / L;
- Possibility of deficiency: between 200pmol / L and 300pmol / L;
- Normal levels: between 300pmol / L and 900 pmol / L.
* pg / ml refers to the picogram per milliliter of blood, which is a unit of measurement, corresponding to 10 -12 grams, where 1 million picograms is equivalent to 0.001 mg (milligram).
In healthy conditions, in order to maintain adequate levels of B12, the diet must consist of products of animal origin.
Foods that have good concentrations of the substance are (every 100g):
- Bovine liver: 65.0mcg;
- Oysters: 14.5mcg;
- Herring (fish): 8.5mcg;
- Lean meat: 5.0mcg;
- Tuna: 4.3mcg;
- Chicken egg yolk: 2.0mcg;
- Chicken eggs: 1.8mcg.
In the case of vegetarians and vegans, the Brazilian Vegetarian Society (SVB) suggests vitamin supplementation in the face of tests that point to nutritional deficiencies, especially in pregnant women, lactating women and when there has already been anemia in the patient’s history.
To understand the impact that vitamin B12 deficiency has on the body, it is interesting to understand the functions of red blood cells, as soon as they are directly affected in the development of pernicious anemia.
Also called erythrocytes, red cells have a biconcave shape and about 34% hemoglobin, which is a protein. Its function is the transport of gases , such as oxygen, to the tissues of the body.
On average, a healthy woman has concentrations of 4.7 million red blood cells, while a man can reach 5.2 million.
The concentration is efficiently regulated by the body, aiming to maintain adequate oxygenation levels to supply the needs of the body’s cells. When there is a decrease in the levels of red cells in the blood, it results in a reduction of oxygen to the tissues.
In healthy conditions, if there is a reduction in the concentration of red blood cells, the body begins a regulatory process by stimulating erythropoietin (a hormone secreted by the kidney and released into the blood).
Thus, there is a stimulus for the production of hemocytoblasts (blood cells), providing that the level of red blood cells and blood oxygenation is restored.
In addition to vitamin B12, folic acid is essential for the correct synthesis of DNA, which ends up impacting the nuclear constitution and cell division of erythrocytes.
When there is a deficiency of any of these substances, the result is fragile red blood cells, of increased size and reduced maturation.
The accelerated death of red blood cells causes a decrease in blood concentration and, consequently, organic dysfunctions, resulting in anemia.
Megaloblastic anemia is characterized by the abnormal size of red blood cells, in addition to reduced life span. There is also a decrease in leukocytes (white blood cells) and platelets.
The body needs the correct intake and absorption of B12 in order to properly divide red blood cells. Without the vitamin, size changes occur in blood cells, which become more fragile and are eliminated more quickly (decreasing their concentration in the blood).
When red cells have increased volume (a condition called macrocytic) and reduced blood concentrations, there is a picture of megaloblastic anemia.
The pernicious anemia is therefore a type of megaloblastic anemia , because the conditions of red blood cells present the same, but there needs to be deficiency or dysfunction of the intrinsic factor.
Pernicious anemia occurs when the lack of vitamin B12 is caused by the absence of the intrinsic factor that, in up to 90% of patients, is associated with autoimmune causes. Thus, even if the vitamin intake is correct, the body is unable to synthesize B12.
In this case, the organism behaves inappropriately, causing the antibodies to attack the parietal cells of the stomach (responsible for the production of gastric acid and intrinsic factor), reducing or inhibiting the secretion of the intrinsic factor.
There are still other factors that affect the reduction, such as the prolonged use of medications, such as antacids and metformin, in addition to patients with alcoholism and who underwent bariatric operations.
In general, most cases are associated with autoimmune atrophic gastritis , in which there is a loss and atrophy of the gastric mucosa, which decreases the production of the intrinsic factor and, consequently, impairs the synthesis of vitamin B12.
Chronic autoimmune gastritis
Also called atrophic gastritis, the disease is characterized when antibodies attack and destroy gastric glands, specifically in the region where the cells responsible for the production of stomach acid and the intrinsic factor are located.
The autoimmune condition can present degrees of inflammation and atrophy of the stomach mucosa, which can favor the appearance of a gastric tumor, which affects between 1% and 7% of patients with pernicious anemia.
Autoimmune intestinal inflammation
The celiac disease can cause malabsorption of nutrients when the diet is not properly followed. This is due to the atrophy of the intestinal mucosa, which is weakened and reduces the absorption of nutrients.
Gastric changes caused or associated with celiac disease can interfere with the correct synthesis of vitamin B12.
In addition, other pathologies may be related to pernicious anemia, such as Crohn’s disease .
Gastric and bariatric surgery
After surgery to remove tumors, gastric problems or bariatric procedures, digestive functions may be impaired.
Gastrectomies are very common types of stomach interventions, and can be total (the whole stomach is removed) or partial (only part of it is removed).
There is a prevalence of pernicious anemia in patients undergoing gastrectomy and other procedures for stomach reduction.
Although it is little known, pernicious anemia can present due to genetic causes.
This condition is called congenital pernicious anemia , in which there is an autosomal recessive disorder, that is, genetically inherited, being characterized by the total or partial absence of production of the intrinsic factor.
In general, congenital pernicious anemia is more prevalent until the 4th month of life, but there are reports of diagnoses in adults over 30 years of age.
The condition is inherited genetically through an autosomal recessive disorder. That is, the child inherits the disease from both parents.
Each parent (father and mother) is responsible for 50% of the genes that cause pernicious anemia.
Pernicious anemia can be associated with several autoimmune conditions of the gastrointestinal tract or not.
This is because the immune system performs different functions. If there is any change in its action, there is a greater tendency for other organs to be affected as well.
Among the most frequent conditions associated with pernicious anemia are:
- Addison’s disease;
- Chronic thyroiditis;
- Methylmalionic acid;
- Dermatite herpetiforme;
- Crohn’s disease;
- Graves’ disease;
- Myasthenia gravis;
- Diabetes type 1;
These conditions can favor the appearance of dysfunctions of the intrinsic factor, resulting in the alteration of vitamin B12 synthesis.
In addition, some studies indicate the prevalence of the following conditions:
Immunoglobulin A (IgA) deficiency
Immunoglobulin is an antibody present in the mucous membranes, such as the nasal and intestinal ones.
When there is a low concentration of this antibody in the tissues, the patient has a condition of selective immunoglobulin A (IgA) deficiency, which is one of the most frequent immunological deficiencies.
The dysfunction can be genetic or caused by other diseases or use of medications. Studies indicate that up to 19% of patients with IgA deficiency have pernicious anemia.
Polyglandular endocrine failure syndrome
The disorder affects several endocrine glands, attacking and reducing the specific functions of each one. The condition is autoimmune, that is, it is the antibodies themselves that cause the dysfunction.
The glands are not always attacked at the same time, but it is often the case that more than one dysfunction occurs together.
Among the affected tissues, there is the gastric mucosa, which has the intrinsic factor produced in an irregular way.
Blind loop syndrome
There are reports in the medical literature pointing to blind loop syndrome as a triggering factor for pernicious anemia.
The condition occurs when a portion of food is stopped in part of the stomach. The body is unable to direct the substance to the proper digestive process and there is a vast proliferation of bacteria.
These bacteria impair the absorption of nutrients and result in complications for the body.
Celiac disease may be associated with pernicious anemia because it is also an autoimmune disease.
There are several cases in which pernicious anemia occurs in patients with celiac disease, but the conditions have no cause-and-effect relationship , according to the Association of Celiacs of Paraná (ACELPAR).
Celiac disease is characterized by gluten intolerance . When eaten, the food attacks the intestine and causes malabsorption of nutrients.
Anemia due to lack of iron and B12 or folic acid are often reported in patients with celiac disease who do not follow the diet correctly, but there is no direct interference in the production of intrinsic factor (which is necessary to characterize pernicious anemia).
Up to 30% of people over the age of 50 have a non-detrimental reduction in the absorption of the vitamin due to atrophy of the gastric wall.
Approximately 2% of these cases are diagnosed with pernicious anemia (when there is no intrinsic factor).
There is a higher frequency in white people with Scandinavian or northwest European descent.
Patients after the age of 40 are also more susceptible to the disease, tending to increase the risks with aging.
In general, pernicious anemia tends to be asymptomatic, that is, there are no noticeable clinical changes. In some cases, the signs are quite scattered and mild, making it difficult to associate with the anemic condition.
The clinical picture may involve the presence of anemia (without diagnosing the pernicious picture), which manifests between 30% and 60% of patients. Gastrointestinal disorders are reported in about 15%, while paresthesias (numbness or tingling in the limbs) and neurological signs occur in up to 28% of the reported conditions.
Mental and emotional signs can also be mentioned, including mental confusion, depression , difficulty concentrating and focusing.
The most reported symptoms include:
- Diarrhea or constipation;
- Loss of appetite;
- Difficulty breathing;
- Swollen or reddish tongue;
- Constant drowsiness;
- Muscle weakness;
- Bleeding gums.
But we must remember that pernicious anemia is a condition that often takes years to manifest symptoms. Some patients may show milder signs, while others develop severe conditions.
It is also worth noting that the majority of cases refer to the autoimmune condition, which can be associated with other autoimmune diseases.
Thus, the symptoms can be quite varied and caused, even, by other pathologies.
The most frequent symptoms, especially at the onset of anemia, involve weakness, weak nails and dizziness.
They are signs that usually identify anemias and can evolve or remain stable for prolonged periods.
Signs of anemia may occur, such as palpitations, headaches, irritability, pallor, weakness, difficulty in breathing.
In some cases, there is the presence of bleeding due to the decrease in blood platelets ( thrombocytopenia ).
The disease decreases the healing capacity, stops bleeding and clotting. Therefore, purple spots (bruises) and weakening of the mucous membranes can occur.
The patient may still have slightly yellow skin and eyes, a condition called jaundice.
In some cases, the tongue may be more red and slightly swollen, with or without pain.
When the patient already has gastritis, symptoms of poor digestion, reflux or stomach weight may occur. The condition is called dyspepsia .
Difficulty concentrating, memory and drowsiness are reported, often associated with psychological symptoms, such as mood swings and discouragement.
Spinal cord degeneration (causing pain in the arms, legs and difficulty in walking), peripheral neuropathy (causing numbness or tingling in parts of the body) and changes in mental status in the most severe cases of the disease can also occur.
The diagnosis can be made and the treatment accompanied by specialists such as general practitioner, nutrologist, gastroenterologist, hematologist, neurologist, proctologist, endocrinologist and otorhinolaryngologist.
When there is suspicion of pernicious anemia, the diagnosis is quite simple, being carried out through blood tests, especially blood count and gastric biopsy to assess the presence of mucosal atrophy.
In general, the blood count is not able to differentiate the types of macrocytic anemias (in which there is an increase in the volume of red blood cells). Thus, changes in the results indicate the presence of the disease, but not its type.
To confirm the diagnosis, it is necessary to carry out tests that verify the presence and rule out other diseases or causes of B12 deficiency.
The procedures aim to diagnose blood and vitamin changes, in addition to gastric changes, injury to the stomach wall or autoimmune conditions that reduce the intrinsic factor.
Usually, the first test to be requested in cases of suspected anemia is the blood count , which presents an overview of globular concentrations.
The complete blood count is capable of analyzing different parts of the blood sample, such as red and white globular concentrations, in addition to platelets.
In addition, the test can check the average volume of the cells, showing whether they are in adequate sizes. As the red blood cells have a larger volume than normal in patients with pernicious anemia, the test helps to determine the type of the disease.
Tests that complement the results may involve the measurement of vitamin B12, the lack of intrinsic factor and the reticulocyte count (immature erythrocytes) and blood level of methylmalonic acid (substance produced in the absence of B12) and homocysteine (amino acid that presents elevations in frames pernicious anemia).
Vitamin B12 levels are not always low, even if there is a deficient synthesis. Therefore, complementary exams are necessary for correct interpretation.
Imaging exams, such as biopsy and digestive endoscopy , allow to find out if there is a lesion in the stomach, such as inflammation and atrophy of the gastric wall, interfering with the secretion of acids and the intrinsic factor.
Test the Schilling
There is also the application of the Schilling test. The exam is performed to differentiate pernicious anemia from megaloblastic anemia. The goal is to measure the dosage of vitamin B12 with and without the intrinsic factor.
The test is still used in some cases, but it has been less recurrent in the diagnosis.
Its performance consists of the administration of 2 doses of vitamin B12, one oral and one injectable, and after 24 hours, the patient’s urine is collected. If urine collection shows small amounts of vitamin B12, it is suggested that there is an intrinsic factor deficiency.
Then the test is repeated by applying, together with the vitamin, an intrinsic factor dosage. If the amount of vitamin B12 found in the urine is greater (or is now at adequate levels), pernicious anemia is diagnosed.
This is because the intake of the intrinsic factor allowed the correct synthesis of the vitamin.
It is still necessary to carry out an accurate diagnosis in order to rule out other pathologies or conditions that may cause B12 deficiency. Among the diagnoses that may resemble or cause pernicious anemia are:
- Thyroid disorders, such as hypothyroidism;
- Vitamin deficiency caused by medications, such as antivirals.
- Decreased production of hydrochloric acid in the stomach, especially in the elderly.
No . Autoimmune diseases are still not curable, and continuous treatment is necessary.
In some cases, the patient needs vitamin supplementation for life, however, there are chances of the condition being stabilized and not requiring continuous use of vitamin B12.
Treatment consists of supplementation with vitamin B12 , and it may be necessary to supply and stabilize other nutritional deficiencies as well.
Supplementation can take place orally or injectable, and in the most severe cases injections are indicated due to the short time of action.
The treatment must be indicated by the doctor, who will prescribe the dosage according to the patient’s clinical condition.
However, the medical literature usually indicates, in general, the use of injectable vitamin B12, once a day, for 1 week, in the dosage of 1,000mcg. After 7 consecutive days, the intake is made once a week, in the same dosage.
After 1 month (that is, 4 weekly dosages), the treatment can be done once a month, maintaining the dosage or making adjustments, according to tests.
Orally, the use of 1,000 mcg daily may be prescribed. However, the medical literature indicates that treatment should be continued daily for indefinite periods.
In cases where there are associated diseases, it may be necessary to resort to the use of antibiotics (when there is blind loop syndrome, for example) or continuous treatments (such as in cases of celiac disease or diabetes).
Although pernicious anemia is caused by the inability to synthesize vitamin B12 ingested through food, maintaining balanced meals can assist in the proper functioning of the body.
If malabsorption is due to other causes or associated diseases, controlling the primary condition can improve vitamin synthesis.
Therefore, it is ideal to include foods of animal origin, as they are the sources of vitamin B12.
The Brazilian Vegetarian Society (SVB) recommends daily intake of the following amounts of B12:
- 0 to 6 months: 0.4mcg;
- 7 to 12 months: 0.5mcg;
- 1 to 3 years: 0.9mcg;
- 4 to 8 years: 1.2mcg;
- 9 to 13 years: 1.8mcg;
- Above 14 years old: 2.4mcg;
- Gestation: 2.6mcg;
- Breastfeeding: 2.8mcg.
There are no fixed values for daily intake, which may vary according to each country. However, the average is 2mcg per day for adults.
B12 can be supplemented with cyanocobalamin based vitamin drugs .
In more severe cases or in the first moments of treatment, injections of B12 may be prescribed.
Supplementation with other compounds, such as folic acid, iron and other vitamins should only be increased with the doctor’s express indication based on the exams of each patient.
NEVER self-medicate or stop using a medication without first consulting a doctor. Only he will be able to tell which medication, dosage and duration of treatment is the most suitable for his specific case. The information contained in this website is only intended to inform, not in any way intended to replace the guidance of a specialist or serve as a recommendation for any type of treatment. Always follow the instructions on the package insert and, if symptoms persist, seek medical or pharmaceutical advice.
Patients with pernicious anemia may experience fatigue and malaise. Therefore, until the treatment eases the symptoms, it may be indicated to avoid physical activities or exhausting exercises.
It is necessary to be attentive to food, maintaining adequate nutritional levels.
Nutritional monitoring is highly recommended, as it is necessary to eat foods rich in vitamin B12 for the body to be able to absorb it during the body’s stabilization.
If treated and properly monitored by the doctor, pernicious anemia generally does not confer complications or risks to the patient’s health.
Whether or not there is a need for continuous treatment, frequent examinations are necessary to check whether the B12 rates are adequate.
Even in aggravated cases, in which neurological disorders are present, most patients show a rapid and significant improvement. Sometimes, symptoms can persist if treatment takes too long to start.
It is also necessary to observe the appearance of other anemic pictures and symptoms. If there is an association of autoimmune diseases, it is necessary to carry out joint treatment.
However, when well controlled and treated, conditions present good responses, making living with diseases easier.
Treatment with vitamin B12 tends to show rapid improvements and the symptoms subside as soon as the vitamin levels start to rise, which can occur between 1 and 2 months.
Prolonged and severe B12 deficiency may, in some cases, favor the appearance of polyps and gastric tumors, in addition to favoring spinal cord degeneration and psychosis .
The risk of stomach cancer is up to 3 times higher in patients with pernicious anemia, especially when gastric atrophy is present.
In severe and prolonged cases, in which the treatment is not carried out, damage to the organism can occur, affecting the heart, nerves and digestive system.
In the nerves, the disease can cause irreparable loss of memory, ability to concentrate, in addition to affecting the senses (such as sight or taste).
When there is damage to locomotion, they can persist in the absence of treatment.
There are no measures to prevent pernicious anemia resulting from autoimmune conditions.
Avoid frequent and prolonged use of antacids or medications capable of inhibiting the proton pump (interfering with the production of the intrinsic factor).
The ideal is to maintain regular appointments and routine exams and, especially patients with autoimmune diseases, to be aware of the symptoms, due to the higher incidence in these cases.
Caring for your diet can help maintain adequate B12 levels and prevent anemia in general.
For patients with dietary restrictions (such as allergic, intolerant or vegetarian and vegan), follow-up with a nutritionist can facilitate dietary adjustments.
In addition, in patients undergoing gastric surgeries, examinations and medical follow-up are necessary to verify that B12 synthesis remains adequate.
Anemias are often directly associated with poor diet or the deficiency of a specific nutrient.
However, even if meals are healthy and balanced, some factors or dysfunctions of the body itself can interfere with the absorption of vitamin B12, causing pernicious anemia.
For example, autoimmune causes, stomach surgeries or the use of antacid medications.
In these cases, even with an adequate diet, the organism is not able to synthesize the ingested substance, causing damage to the health and the proper functioning of the whole body.
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