• Cells in the raphe nuclei of brainstem convert L-tryptophan by tryptophan hydroxylase (TPH) to 5-hydoxytryptamine (5-HTP), and furtherly, by amino acid decarboxylase (DDC) to serotonin (5-HT). This is broken down by monoamineoxidase (MAO) to 5-HIAA. Serotonin is released into the synapse in a similar fashion to norepinephrine. Two presynaptic serotonin receptors serve as both brakes and enhancers of serotonin release when blocked by serotonin or norepinephrine, while the postsynaptic receptors regulate the release of the serotonin signal into the neuron. Serotonin producing neurons extend to the cerebellum, basal ganglia, frontal cortex, amygdala, thalamus, hypothalamus and limbic system, and down the spinal cord.  TPH1 is in several tissues, and TPH2, is a brain-specific isoform. Ovarian hormones can affect the expression of TPH (postpartum depression and premenstrual stress syndrome).
• Enterochromaffin cells in the gastrointestinal tract
• Platelets

Picture 1. Serotonin synthesis

Serotonin Effects

Serotonin effects include:

• Serotonin is found in the GI tract,… from mood to anxiety to sleep (serotonin makes melatonin, which regulates sleep) to sexual response to food craving and (in)digestion.
• Intestinal serotonin may inhibit bone formation (2)
• As a neurotransmitter: modulation of anger, aggression, body temperature, mood, sleep, human sexuality, appetite, and metabolism, as well as stimulating vomiting  (2).
• In platelets - post-injury vasoconstriction
• Nausea/vomiting (Dolasetron blocks serotonin so it helps in nausea)

What Affects Serotonin Release?

This:

• Serotonin transporter  facilitates re-uptake of serotonin into presynapses
• Exercise

Substances with Serotogenic Action:

Serotonergic action is terminated primarily via uptake of 5-HT from the synapse. This is through the specific monoamine transporter for 5-HT, SERT, on the presynaptic neuron. Various agents can inhibit 5-HT reuptake including (2):

• The empathogen MDMA (ecstasy) releases serotonin from synaptic vesicles of neurons.
• Amphetamine
• Cocaine
• Dextromethorphan (an antitussive)
• Tricyclic antidepressants (TCAs)
• Selective serotonin reuptake inhibitors (SSRIs) (2).
• The psychedelic drugs psilocin/psilocybin, DMT, mescaline, and LSDare agonists primarily at 5-HT_2A receptor.
• MAO inhibitors
• Tryptophan and5-hydroxytryptophan (5-HT) cross blood-brain barrier and are converted to serotonin
• Some cancers(carcinoid) secrete serotonin or 5-HIAA

Foods High in Serotonin

These include:

• Nuts of the walnut (Juglans) and hickory (Carya) genuses
• Plantain, pineapple, banana, kiwifruit, plums, and tomatoes.
• Fish, chicken and turkey
• Avocado
• Whole meal bread
• High-fibre cereals
• Tryptophan is found in bananas, pineapples, plums, turkey and milk

What is required to increase serotonin production is an increase in the ratio of tryptophan to phenylalanine and leucine. Fruits with a good ratio include dates, papaya and banana. Foods with a lower ratio inhibit the production of serotonin. These include whole wheat and rye bread.

Low Serotonin

• Problems with concentration and attention (1)
• Depression
• Chronic fatigue
• Nonrefreshed sleep; we can’t go to sleep at night as our mind/thought is racing ( “My mind won’t shut up!” ); early-morning awakening
• Loss of appetite and subsequent weight loss or a craving for sweets and carbohydrates when the brain is trying to make more Serotonin.
• Total loss of sexual and other interest is present. In fact, there is loss of interest in everything
• People whose serotonin levels have been artificially lowered will reject unfair offers 

References:

1. http://www.enotalone.com/article/4116.html
2. Serotonin inhibits bone formation http://en.wikipedia.org/wiki/Serotonin
3.  Exercise releases serotonin  (serendip.brynmawr.edu)

Vit D effects:

• Enhances absorption of calcium, phosphate, and magnesium from the small intestine (when stimulated by PTH) by increased synthesis of calcium binding protein
• Enhances reabsorption of calcium and phosphate in the kidneys (with the help of estrogen and PTH)
• Enhances resorption of calcium and phosphorus from the bones (when stimulated by PTH)
• Stimulates insulin production in the pancreas

Dietary Sources of Vitamin D

Dietary sources:

• Fish oil
• Salt water fish
• Fortified milk, orange juice, morning cereals

Metabolism of Vitamin D

Vit D2 (ergocalciferol or ergosterol) is obtained by diet, from plants.
Vit D3 (cholecalciferol) is produced in the skin from 7-dehydrocholesterol under UV influence.
Calcidiol or calciferol or 25-hydroxycholecalciferol [25(OH)D] or 25-D is synthesized in the liver from vit D2 and D3. Half-life of calcidiol is several weeks. 25-D is in vitamin D supplemments.

All above forms of vitamin D are inactive.

Calcitrol or 1,25-dihydroxycholecalciferol  [1,25(OH)D]  is synthesized in the kidneys from calcidiol by the help of PTH and is the only active form of vitamin D. Half-life of calcitrol is few hours. Synthesis of calcitrol is enhanced in kidneys by hormone PTH and low blood phosphate. 

Causes of Vitamin D Deficiency

• Low vitamin D intake - but only in inadequate sun exposure (less than 30 minutes a week)
• Inadequate exposure to ultraviolet light (winter, bedridden persons)
• Anticonvulsant-drug therapy (Phenytoin) (1)
• Renal dialysis
• Renal disese: nephrotic syndrome
• Hypertension
• Diabetes mellitus, insulin resistance
• High serum concentrations of parathyroid hormone and alkaline phosphatase
• Low serum concentrations of ionized calcium and albumin   

What Blocks Activation of Vitamin D?

Vitamin D has to be chenged into vit 25D in the liver and furtherly into 1,25D in the kidneys to become active. What can block this activation:

• Vit D to 25D conversion may be blocked by liver disease
• 25D to 1,25D conversion may be blocked by hormone calcitonin or kidney disease 

Symptoms of Vitamin D Deficiency

Symptoms:

• Musculoskeletal pain
• Rickets in children
• Osteomalacia in adults (non-adequate mineralization of bones) 

Vitamin D deficiency can contribute to development of multiple sclerosis or inflammatory bowel disease (3).

References:

1. Phenytoin supposedly caused osteomalacia  (ncbi.nlm.nih.gov/pubmed)
2. Vitamin D (ods.od.nih.gov)
3. Low vitamin D causes MS and IBD  (ncbi.nlm.nih.gov/pubmed)
4. Vit D stimulates insulin production  (merck.com)

Cholesterol is present in the blood and in most of cells, and is a part of substances called lipids. In the blood, cholesterol is bound to certain proteins what makes lipoproteins. Roughly, they are two types of lipoproteins:

• LDL = Low Density Lipoproteins that contain a lot of cholesterol (what makes them low density). This is denoted as LDL cholesterol and is called “bad” cholesterol since, when in excess, it deposits on the inner arterial walls, building plaques called atheromas that harden and clog arteries. The disorder is known as atherosclerosis (from Greek atheroma = cholesterol plaque; sclerosis = hardening of arterial wall).
• HDL = High Density Lipoproteins that contain small amount of cholesterol denoted as HDL cholesterol that takes excessive cholesterol from LDL and carry it away from the blood, so it is called “good” cholesterol. 

Blood cholesterol is uptaken by cells that use it to build cell membranes, hormones, vitamin D and bile acids among other. It is good to have some cholesterol of both types in the blood.

High level of LDL cholesterol in the blood is a strong risk factor for atherosclerosis that is a major cause of stroke and heart attack. 

How to Lower High LDL Blood Levels?

By exercise and some restriction in diet.

Exercise

Exercising for at least 30 minutes a day every day helps to reduce LDL holesterol level in the blood. Any exercise that speed up your heart rate and is appropriate to your health status and age can be helpful.

Diet

 and related juices

Foods to avoid in high LDL:

• Red meat, especially pork, and other fatty meat
• Egg yolk
• Dairy like whole fat milk, cheese, butter, cream
• Products with trans fats like margarines and chips with “hydrogenated fats”
• Chocolate, cocoa

To try:

• Oatmeal
• Morning cereals
• Whole grains
• Whole meal or whole grain bread
• Salads
• Rice
• Potatoes
• Pasta
• Plant sterols and stanols (added in fortified foods like orange juice)
• Fruits like bananas and citruses
• Vegetables like salads, legumes

References:

1. How to lower cholesterol  (ehealthmd.com)

Testosterone:

• In puberty helps a boy in growth of the penis and testes, growth of facial and pubic hair, deepening of the voice, increase in muscle mass and strength, and increase in height.
• In adult man maintains sex drive, sperm production, male hair patterns, muscle mass, and bone mass
• Lowers blood sugar
• Increases bone mineral density in elderly men (1)

Testosterone Conversion

Testosterone converts to (5, page 24):

• Dihidrotestosterone (in testis, liver, brain, prostate, external genitalia)
• Androsterone
• Androstenedione
• Estradiol (in testis, liver, brain)
• Glucuronide
• Etiocholonolone

What Affects Steroid Production?

Below is the scheme of synthesis of steroid hormones (click image to enlarge it).

Substances and enzymes affecting steroidogenesis (5):

• Hydrogene peroxide (H2O2) (blocks conversion of pregnenolone to progesterone)
• Nitrous oxide  (NO) (blocks steroid production)
• StAR (Steroid Acute Regulator) gene codes StAR protein that transfer cholesterol into mitochondria. Growth hormone, estradiol, calcium, and IGF-1 upregulate StAR gene, thus enhancing steroid production.
• Enzyme P450SCC converts cholesterol into pregnenolone (in mitochondria)
• Enzyme 3ßHSD converts pregnenolone to progesterone, and DHEA to androstenedione (3ß-HSD is stimulated by FSH, via LH)
• 5? reductase converts testosterone to dihydrotestosterone (DHT)
• Aromatase converts testosterone to estradiol 
• Substances affecting steroidogenesis (5, pages 34-35)
• Dioxine (fatty meats, dairy) > low testosterone, and limited prostate growth
• Aminoglutethimide > low testosterone
• Lead, cadmium > low testosterone

What Affects Testosterone Blood Levels?

The following (1):

• Gonadotropin Releasing Hormone (GnRH) from hypothalamus stimulates secretion of LH
• LH  from pituitary gland stimulates secretion of testosteron from testes
• Testosterone suppresses the release of GnRH from the hypothalamus (negative feedback)
• Low testosterone production:
  • Chronic illness
  • Delayed puberty
  • Hypopituitarism
  • Prolactinoma
  • Testicular failure
• Steroid Hormone Binding Protein (SHGB) binds testosterone in blood. Increased SHGB lowers free testosterone in blood.
• Obesity – enzyme aromatase in fat tissue converts testosterone in estradiol thus lowering testosterone
• Zinc increases  testosterone level
• A bioflavonoid called chrysin (in honey) has shown potential as a natural aromatase inhibitor. The Life Extension Foundation has identified a novel supplement called piperine that increases the bioavailability of chrysin
• Carnitine
• Muira puama
• Quercetin in red wine inhibits aromatase thus elevating testosterone
• Antioxidants (vitamin A, and E, zinc, and selenium) all support testosterone production 

Low Testosterone (Androgen Deficiency)

Symptoms of low testosterone (2,3):

• Decreased sex drive (libido)
• Inadequate erections
• Increased breast size and tenderness
• Afternoon fatigue
• Symptoms similar to menopause in women (e.g., hot flashes, increased irritability, inability to concentrate, depression)
• SEVERE ANDROGENE DEFICIENCY:
• Loss of body hair
• Loss of muscle mass
• Fragile bones
• Smal and soft testes

Lab Results in Low Testosterone (4)

• Decreased bone density by dexa scan 
• Loss in height of more than 1 inch.
• High blood pressure and heart enlargement with associated chest pain
• Increase in abdominal girth with 40” as maximum for men and waist size of in excess of 34 inches in women
• Low Free Testosterone, occasionally low total testosterone, and low normal bioavailable testosterone
• Loss of penile reflexes and decreased penis sensitivity
• Lowered sperm count and fertility
• Insulin resistance
• High blood glucose
• Below normal HDL
• Low SHBG

References:

1. Testosterone increases bone density in elderly men  (lef.org)
2. Symptoms of low testosterone  (hormone.org)
3. Symptoms in severely lowered testosterone  (nlm.nih.gov/medlineplus)
4. Lab results in low testosterone  (wellnessmd.com)
5. Steroidogenesis of sex hormones  (epa.gov/endo)

• Increases Basal Metabolic Rate (BMR) > increased heat production 

Hypothyroidism

What Lowers TSH Release (1)

Pituitary (hypophysis) hormone TSH (thyroid stimulating hormone) stimulates thyroid to release thyroxine (T4) and triiodothyronine (T3). T4 and T3, when they reach a certain level, lower release of TSH by negative feedback loop. In low T4/T3 (hypothyroidism) TSH will be high, and in high T4/3 (hyperthyroidism) TSH will be low (1). Other factors that lower TSH level:

• Long term stress
• Prolonged cortisol excess
• Aging
• Infection
• Fever
• Trauma
• Caffeine
• Somatostatin
• Dopamine or L-dopa
• Adrenaline (sometimes)
• Amphetamine

Above factors may cause that TSH will be normal, despite hypothyroidism (2).

Symptoms of Hypothyroidism (3):

• Fatigue
• Insomnia
• Depression
• Anxiety and panic attacks
• Decreased memory
• Inability to concentrate
• Weight gain
• Fluid retention
• Puffy face, swollen eyelids
• Dull facial expression
• Swollen legs and feet, swollen hands, swollen abdomen
• Carpal tunnel syndrome
• Constipation
• Headaches
• Brittle nails
• Dry skin
• Elbow keratoses
• Yellowish discoloration of the skin
• White patches on the skin (vitiligo)
• Diffuse hair loss
• Coarse dry hair
• Menstrual irregularities
• Poor circulation
• Muscle and joint pain
• Morning stiffness
• Muscle cramps
• Reduced heart rate
• Low blood pressure
• Slow movements
• Decreased sexual interest
• Low body temperature
• Cold intolerance, cold hands and feet
• Husky voice
• Increased LDL

Thyroid Function and Cortisol

Cortisol controls thyroxine activation at the cell level. Often, symptoms of hypothyroidism are due to adrenal hormone imbalances. If a trial of thyroid hormone resulted in significant but temporary relief of symptoms of hypothyroidism, blood cortisol levels and rhythm should be checked (4).

References:

1. Thyroid function  (endocrineweb.com)
2. What lowers TSH release  (doctorsaredangerous.com)
3. Hypothyroidism symptoms  (worldhealth.net)
4. Cortisol influence on thyroxine activity  (nutrition4health.org)

• Low body temperature for at least one month, at least 0,5°C (0,9°F) lower than your usual temperature
• Low appetite
• Fatigue
• Weigh gain
• Skin Rash…

..then you might have:

1. Lowered thyroid function (Hashimoto’s thyroiditis)
2. Increased adrenal funcion (Cushing’s syndrome)

Low Appetite in Healthy People

1. Normal aging

Psychic/Emotional Causes

1. Emotional stress: anxiety, depression, grief or loss, relationship problems
2. Physical stress
3. Anorexia nervosa
4. Bipolar disorder
5. Bulimia
6. Social isolation

Infections

1. Childhood infections
2. Viral hepatitis 
3. Hemorrhagic fever
4. Bacterial endocarditis
5. Cyclosporiosis
6. Typhoid fever
7. Tuberculosis
8. Urinary tract infection
9. Other acute or chronic infections

Fever

1. Rheumatic fever
2. Still’s disease – systemic onset juvenile rheumatoid arthritis (JRA)

Nausea

Alcoholism

Smoking

Conditions and Diseases

1. SWALLOWING DIFFICULTIES: mouth pain, sore throat
2. STOMACH/DUODENUM: hiatus hernia, stomach/duodenal cancer or ulcer, pernicious anemia, gastroparesis
3. BOWEL: constipation, malabsorption, celiac disease, intestinal parasites/worms, colorectal cancer, inflammation (Crohn’s disease), infection (food poisoning)
4. APPENDIX: appendicitis
5. LIVER: viral hepatitis, cirrhosis
6. GALLBLADDER
7. HEART: congestive heart failure
8. HORMONES: diabetes mellitus, hypo/hyperthyroidism, hyperparathyroidism, adrenal insufficiency, hypopituitarism, APECED (Autoimmune PolyEndocrinopathy, Candidiasis, and Ectodermal Dysplasia)
9. KIDNEY: uremia
10. LUNGS: chronic pulmonary disease, pneumonia by Pseudomonas aeruginosa, psittacosis, silicosis
11. PANCREAS: pancreatitis
12. NERVES: transverse myelitis

General Diseases Affecting the Whole Body

1. DEHYDRATION
2. CANCER: metastases, lymphoma
3. BLOOD: anemia, leukemia

Nutrient/Vitamin Deficiencies

1. Malnourishment
2. Zinc deficiency
3. Milk-alkali syndrome – hypercalcemia, caused by excessive milk and calcium carbonate antacids consuption
4. Beriberi -vit B1 (thiamine) deficiency – in chronic alcoholics: tingling and numbness in  hands and feet; if heart is affected: shortness of breath on exercise, legs swelling
5. Dilutional hyponatremia. Causes: heavy vomiting or diarrhea, diuretics, heart failure, kidney disease, cirrhosis
6. Hypercalcemia
7. Hypomagnesemia
8. Arginase (enzyme that breaks down amino acid arginin) deficiency – inborn disorder, causes accumulation of arginin and ammonium in the body – muscle stiffness, shows up around age of 3. 
9. N-acetyl glutamate synthetase (NAGS) deficiency – a rare genetic disorder where a lack of enzyme causes ammonia accumulation in the blood

Pregnancy

1. Pregnancy itself
2. Acute fatty liver of pregnancy

Medications

1. Antibiotics
2. Glucocorticoids
3. Iron supplements
4. Antithyroid drugs (methimazole, propylthiouracil)
5. Oral contraceptives
6. Oral hypoglycemics
7. Tamoxifen
8. Cough and cold preparations
9. Codeine and Morphine
10. Demerol
11. Digitalis
12. Chemotherapeutic agents
13. Ephedrine and other sympathomimetics
14. Medications causing liver damage: chlorophorm, cyclopropane, ether, halothane, methoxyflurane, nitrous oxide, chloramphenicol, phenobarbital, 5-Fluorocytosine, metronidazole, ethionamide, vidarabine 
15. Amphetamine intoxication
16. Anabolic C-17

Poisoning

1. Lead
   • Lead pipes, old paints, house dust
   • Cosmetics, or remedies containing some traditional herbs: kohl, surma, bali goli; deshi dewa, ghasard, kandu, cordyceps, Hai Ge Fen, rueda, alacron, liga, Maria Luisa, etc
2. Herbal agent adverse reaction: chaparral, foxglove, henna, kombucha, cottonseed, garlic, germanium
3. Aluminium
4. Arsenic
5. Barium
6. Bismuth
7. Bromide
8. Cadmium
9. Chromium
10. Copper
11. Cresol
12. Cyclopropane
13. Glaze
14. Gold
15. Iron
16. Mercaptans
17. Mercury
18. Nickel
19. Selenium
20. Solder
21. Steroids
22. Thallium
23. Tin
24. Uranium
25. Ecstasy abuse 
26. Heroin withdrawal
27. Marijuana withdrawal
28. Aflatoxin- secreted by fungi on cereal (maize, sorghum, pearl millet, rice, wheat), oilseeds (groundnut, soybean, sunflower, cotton), spices (chillies, black pepper, coriander, turmeric, zinger), tree nuts (almonds, pistachio, walnuts, coconut) and milk
29. Radiation sickness

What to Do?

• Have small frequent meals
• Eat caloric foods you like
• Eat with others
• Have a breakfast
• Consider treating or overcoming the cause of low appetite

References:

1. What to do in low appetite? (cancer.org)

Introduction

The aim of this article is to help to explain results of tests of EBV (Epstein-Barr virus) antibodies levels in the  blood .

The main reason for elevated EBV antibodies in the blood is infectious mononucleosis (IM). 95% of us were probably infected with EBV at some point in life, but only some of us had notable symptoms of IM (1).

ACUTE Infectious Mononucleosis

Adolescents and young adults with IM typically develop fever, sore throat, and enlarged (palpable) lymph nodes in the neck, armpits and groin 30-50 days after infection. Infants, and children under 10 years of age often don’t show any symptoms of IM after infection with EBV. Severity of infection tends to increase with age. Old people often develop hepatitis (without jaundice), but not sore throat and enlarged nodes. Symptoms usually lasts for 1-2 months (seldom over 4 months) and then in most cases resolve without any consequences. Blood serum shows:

• Normal to moderately elevated WBC (white blood cells)
• Increased % of lymphocytes (a type of white blood cells) among which there are at least 10% of atypical lymphocytes

Antibodies that are raised in blood serum in ACUTE EBV infection:

• VCA-IgM (IgM antibodies to EBV Viral Capsid Antigen) appear first, disappear in 4-6 weeks, but may persist for about 1 year.
• VCA-IgG (IgG antibodies) appear within a week of infection, then it persists for life. Rising VCA-IgG levels tends to indicate an active EBV infection, while falling concentrations tend to indicate a recent EBV infection that is resolving.
• EA-D-IgG (IgG antibodies to EBV Early Antigen Diffuse) are positive in about a week, usually gone in 2 weeks, persists in 20% of people.
• Heterophile antibodies (“monospot” and Paul-Bunnell test (2)) appear after 7-14 days (meaning that on the beginning they are negative), and decline after 4th week, and may sometimes persist for 1 year. These antibodies, together with atypical lymphocytes and symptoms, are considered as confirmation of infectious mononucleosis. Heterophile antibodies do not appear in about 10% of adults in about 50% of children. Heterophile test also have some false positive and negative results though. If a person has negative mono spot test, but symptoms consistent with IM, specific antibody tests (see above) are needed to confirm EBV infection. Heterophile-negative infectious mononucleosis may be also caused by HIV, HHV-6, toxoplasmosis, CMV, rubella, or anicteric viral hepatitis.
• VCA-IgA = IgA antibodies to the EBV Viral Capsid Antigen
• EA-R-IgG = IgG antibodies to the EBV Early Antigen Restricted

Explanation. Presence of VCA-IgM and absence of EBNA-IgG antibodies speak for acute EBV infection.

Someone who was infected at any point in the life, having symptoms or not, will not develop symptoms of IM after next exposure to EBV.

LATENT EBV Infection (Indicates PAST Infection)

After acute EBV infection, EBV virus remains dormant (sleeps) in epithelial cells of the throat, in nervous tissue, and in B lymphocytes in the blood. Virus in B lymphocytes doesn’t overgrow, since it is controlled by T lymphocytes that destroy infected B lymphocytes on the regular basis. This latent phase is harmless, there’s no symptoms, and it persists for life. This is not a disease and no treatment is needed. The major hallmark of this phase is appearance of EBNA-IgG antibodies.

Antibodies that are raised in blood serum in LATENT EBV infection (they indicate PAST infection):

• EBNA-IgG= IgG antibodies against EBV Nuclear Antigen appear 2 to 4 months (sometimes in first weeks) after onset of symptoms, and persists for life
• VCA-IgG- IgG antibodies against EBV Virus Capsid Antigen appears after the first week of onset of symptoms and persists for life
• (EA-D-IgG persists in 20% of people with past EBV infection)

Explanation. In latent infection, IgG antibodies are present, and IgM antibodies are absent. Latent infection speaks for PAST infection that occurred at least 4-6 months before testing.

REACTIVATED EBV Infection

In a person who was infected once in the life (having symptoms or not), raise of EBV antibodies in blood serum may be triggered by stress or disease. Typical symptoms of IM may appear or not.

Antibodies that are raised in REACTIVATED EBV infection:

• VCA-IgM
• EA-IgM
• VCA-IgG
• EA-D-IgG = antibodies against EBV Early Antigen – Diffuse. Antibodies against EA are present in the blood serum due to EBV virus that was dormant in the body and was reactivated, OR due to their persistence after acute EBV infection.
• EBNA-IgG

Explanation. Both IgM antibodies that speak for active infection, and EBNA-IgG that speak for past infection, are present.

CHRONIC Active Infectious Mononucleosis

In persons with symptoms lasting over 6 months, specific EBV antibodies that would confirm active chronic EBV infection are rarely found in the blood serum. These are possible reasons:

• Symptoms are of psychic nature
• Symptoms are caused by other causes like cytomegalovirus (CMV), toxoplasmosis, viral hepatitis, etc.

EBV antibodies in blood serum in CHRONIC EBV infection:

• VCA-IgG
• EBNA-IgG
• EA-D-IgG
• EA-R-IgG

Explanation. Absence of Ig-M antibodies, and persistence of EA-D and EA-R antibodies for over the year speaks for chronic EBV infection.

Criteria for Different Types of EBV Infection

In below table there are possible combinations of EBV antibodies tests results in different types of EBV infection (15):

• CURRENT ACUTE EBV infection:
  • {VCA-IgM and EA-IgM positive, VCA-IgG and EA-IgG positive, EBNA-IgG negative} or
  • {VCA-IgM and EA-IgM positive, VCA-IgG and EA-IgG negative, EBNA-IgG negative} or
  • {VCA-IgM and EA-IgM negative, VCA-IgG and EA-IgG positive, EBNA-IgG negative}
• PREVIOUS EBV infection:
  • {VCA-IgM and EA-IgM negative, VCA-IgG, EA-IgG, and EBNA-IgG positive} or
  • {VCA-IgM and EA-IgM negative , VCA-IgG and EA-IgG negative, EBNA-IgG positive}
• REACTIVATION of EBV infection:
  • {VCA-IgM and EA-IgM positive, VCA-IgG, EA-IgG, and EBNA-IgG positive} or
  • {VCA-IgM and EA-IgM positive, VCA-IgG and EA-IgG negative, EBNA-IgG positive}
• CHRONIC EBV infection:
  • EBNA-IgG and VCA-IgG positive, EA-D-IgG possibly positive, all IgM antibodies negative

CONDITIONS With Elevated EBV Antibodies

1. ACUTE INFECTIOUS MONONUCLEOSIS. If you have VCA-IgG, EA-IgG, and all igM positive, and EBNA-IgG negative, and if you’re child or young adult with symptoms (sore throat, fever, enlarged lymph nodes), you probably have acute infectious mononucleosis. As mentioned, symptoms may be absent.

2. INFECTION WITH EBV IN THE PAST (LATENT INFECTION). If EBNA-IgG,VCA-IgG, and maybe also EA-IgG are positive (with levels as expected), and all IgM antibodies are negative, this ONLY means you’ve been infected with EBV virus at some point of your live, so this is an evidence of PAST infection. This result by itself is not a sign of any disease; most of adults in western world will have this result.

But if above antibodies are unusually high (“off the chart”), it is possible that they were triggered by one of disorders from below list (including stress).

3. REACTIVATION OF EBV INFECTION. If you have positive EBNA-IgG, and positive VCA-IgM, this is a sign of reactivation of your past infection, and you may experience some or all (or none) symptoms of acute IM. This reactivation may, again, be due to stress or a disease from below list, so you may also have symptoms of this disease.

4. CHRONIC EBV INFECTION. If you had confirmed acute infectious mononucleosis, and your symptoms persists for over 6 months, and if you have positive VCA-IgG, EBNA-IgG, EA-R, and EA-D antibodies, then it’s possible you have chronic infectious mononucleosis. Again, this type is rarely confirmed with lab tests, so it’s likely your symptoms are of psychic nature, represent complications of EBV infection, or are from some disease listed below.

5. LIST (incomplete) OF DISORDERS THAT MAY BE ASSOCIATED WITH INCREASED LEVEL OF EBV ANTIBODIES IN THE BLOOD SERUM. It is not always clear, if EBV virus has caused these disorders, or elevated EBV antibodies are result of these disorders.

• Stress (psychical or physical stress, or an ilness)
• Herpangina (4) (mouth blisters in young children, caused by coxsackieviruses or enteroviruses; )
• Mercury and chronic viral ilnesses
• Corneal subepithelial infiltrates (4)
• Toxoplasmosis (positive heterophile antibodies)
• Mycoplasma pmeumoniae (causes atypical pneumonia, can reactivate EBV infection) (9)
• Mycoplasma fermentans and raised EBV antibodies
• Rheumatoid artritis (positive rheumatoid factor)
• Sjögren’s syndrome (positive ANA and SSA (RO, and SSB (LA) antibodies)
• SLE (4) (positive antinuclear antibodies (ANA))
• Polymyositis and dermatomyositis (6) (muscle pain and weakness, elevated muscle enzymes)
• Lyme disease (red circular rash at the site of the tic bite, antibodies against Borellia (Western Blot test positive only in ~70%)
• Brucellosis (bacterial disease transmitted from farm animals)
• HHV-6 (HHV-6 is a virus from a Herpes family, may be connected with multiple sclerosis or CFS)
• CMV- cytomegalovirus
• Autoimmune thyroiditis (6) (Enlarged thyroid, lowered thyroxine in Hashimoto’s thyroiditis)
• Autoimmune hepatitis (6) (Fatigue, enlarged liver, positive ANA antibodies)
• Kawasaki’s disease (6) (Vasculitis in small children: red eyes, lips, tongue, palms and soles, fever > 5 days)
• Multiple sclerosis (elevated VCA-IgG (5), elevated VCA-IgG, EBNA complex, EBNA-1/2 (7))
• Virus induced CNS dysfunction (VICD)
• Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
• CFS (elevated VCA-IgG and EA-D-IgG, low EBNA-IgG). EBV does not cause chronic fatigue syndrome.
• Cellular imunodeficiencies (including AIDS)
• Post-transfusion syndrome (10)
• Hemophagocytic syndrome (9) (prolonged fever, enlarged liver and spleen, decreased levels of cells in blood (cytopenia))
• Severe mosquito allergy (9)
• Interstitial Lung Disease (12) (shortness of breath and dry cough, may be caused by viruses, mycoplasma, long term exposure to silica fibers, etc, Dg is with chest X-ray)
• Lymphoma
• Primary cerebral lymphoma (4)
• B-cell lymphoma in immunocompromised patients (10)
• Hodgkin’s disease
• Non-Hodgkin’s Lymphoma (NHL)
• Increased risk for NHL, associated with PCBs, chlordanes, TBDE, and HCB (11).
• Burkitt’s lymphoma – rare
• Nasopharyngeal carcinoma – rare (4)
• Breast cancer (9)
• Gastric carcinoma (13)
• Lymphoepithelioma like lung cancer (14)
• Chronic Lymphocitic Leukemia (CLL) (9)
• X-Linked Lymphoproliferative Syndrome (9)
• Smooth muscle tumors
• Hairy Leukoplakia, which means that HIV Infection has to be considered
• Stevens-Johnson syndrome (4)
• Alice in Wonderland syndrome (4)
• Post-transplant lymphoproliferative disorder (4)
• CMV-like disease in renal transplant recipients (10)
• Kikuchi’s disease (4) 

References:

1. Phases of EBV infection (cdc.gov)
2. Mono spot test (heterophile antibodies) (drugs.com)
3. Phases of EBV infection with accent on latent phase (detailed) (uq.edu.au)
4. Some disorders related to EBV  (newworldencyclopedia.org)
5. Multiple sclerosis asociated with EA and VCA antibodies (direct-ms.org)
6. Autoimmune hepatitis/thyroiditis, polymiositis, Kawasaki – EBV antobodies (medscape.com)
7. Antibodies in multiple sclerosis: VCA-IgG & EBNA (mult-sclerosis.org)
8. EBV antibodies (labtestsonline.org)
9. EBV and other diseases (smokershistory.com)
10. EBV antibodies in CFS (palpath.com)
11. PCBs and elevated EA IgG (safe2use.com)
12. EBV causes interstitial lung disease (smokershistory.com)
13. Gastric carcinoma (smokershistory.com)
14. Lymphoepithelioma like lung cancer (smokershistory.com)
15. EBV antibody levels in various phases of EBV infection explained (pubmedcentral.nih.gov)

Useful links:

• Viral pharyngitis – possible causes (emedicine.medscape.com)
• EBV and Infectious mononucleosis (aafp.org)
• Multiple sclerosis and EBV (jama.ama-assn.org)

This article is for educational purpose, and can not be a substitute for a doctor’s advice.