Lyme Disease

This article is written especially for Mary D. Martinez, my twitter friend




Lyme disease is also known as Lyme borreliosis, defined as an infectious disease as the result of the bite of the infected black legged tick, fed on mice, squirrels, birds and other small animals carrying the bacterium. In US, the disease is mostly caused by bacteria Borrelia, a genus of bacteria of the spirochete phylum. The bacteria can spread throughout the body as it has been found in the skin, heart, joint, peripheral nervous system, and central nervous system, according to "The emergence of Lyme disease" by Allen C. Steere, Jenifer Coburn, and Lisa Glickstein. (a)

Ten Facts You Should Know About Lyme Disease, quoted from the IDSA(b)

1. Lyme disease is caused by bacteria called Borrelia burgdorferi that is only transmitted to humans when they are bitten by an infected tick.
   
2. To infect its host, a tick typically must be attached to the skin for at least 36 hours.
   
3. Most cases of Lyme disease occur in late spring and early summer.
   
4. The most common symptoms of Lyme disease include a red, circular “bulls-eye” rash often accompanied by muscle and joint aches. About 70 to 80 percent of people infected develop the rash, which shows up several days to weeks after the tick bite.
   
5. Lyme disease is diagnosed by medical history, physical exam, and sometimes a blood test. It may take four to six weeks for the human immune system to make antibodies against Borrelia burgdorferi and therefore show up in a positive blood test. That is why patients with the Lyme rash usually have a negative blood test and diagnosis is based on the characteristic appearance of the rash. Patients with other clinical manifestations such as Lyme arthritis will usually have a blood test. Anyone who has symptoms for longer than six weeks and who has never been treated with antibiotics is unlikely to have Lyme disease if the blood test is negative.
   
6. Most cases of Lyme disease are successfully treated with a few weeks of antibiotics. Using antibiotics for a very long time (months or years) does not offer superior results and in fact can be dangerous, because it can cause potentially fatal complications.
   
7. Approximately 95 percent of all cases of Lyme disease occur in the Northeast and the Upper Midwest.
   
8. Researchers didn’t identify the cause of Lyme disease and connect it with ticks until 1981. The bacterium that causes the disease is named in honor of Willy Burgdorfer, the scientist who made the connection.
   
9. There were nearly 30,000 confirmed cases of Lyme disease in 2009 and more than 8,500 probable cases. The number has risen steadily since 1995, when there were only 11,700 confirmed cases.
   
10. The best treatment for Lyme disease is prevention: Be cautious when walking in the woods, avoiding bushy and grassy areas. Wear long pants and long-sleeved shirts and wear insect repellent containing DEET on exposed skin. After walking in wooded areas, thoroughly check the skin for the poppy-seed sized ticks, paying particular attention to the scalp, armpits and groin. If you find a tick, carefully remove it with tweezers.
    

I. Symptoms
Symptoms of Lyme disease can be classified in 3 stages
A. Stage I
Erythema chronicum migrans or skin rash is one of most common symptom of the early stage of Lyme disease, often happened few days to a month after the tick bite as a result of skin infection , according to "Erythema migrans and early Lyme disease" by Nadelman RB, Wormser GP.(1)
Other symptoms include
1. Fatigue
It is either the result of the immune system engage in the fighting off the infected bacteria or the use of antibotic in treating the disease. It sometime can be mistaken as chronic fatigue syndrome or vice versa, according to "Post-treatment Lyme disease syndrome symptomatology and the impact on life functioning: is there something here?" by Aucott JN, Rebman AW, Crowder LA, Kortte KB.(2)

2. Chills or fever
As the result of high fever or fever due to immune system response to the infectious bacteria.

3. Persistent headache
As the disease has cause the affects on the cognitive function as the result of increased intracranial pressure, according to "Lyme disease presenting with persistent headache" by Moses JM, Riseberg RS, Mansbach JM.(3) and researchers indicated that increased intracranial pressure in association with neuroborreliosis can lead to blindness.

4. Muscle and joint pain
It is most common symptom of the patient with Lyme diseases in the early stage, if it is left untreated it can become more serious form of Lyme arthritis. Sometime it is mistaken as Parsonage-Turner syndrome, with with acute shoulder pain followed rapidly by weakness and wasting of the shoulder girdle muscles, according to "Parsonage-Turner syndrome revealing Lyme borreliosis" by Wendling D, Sevrin P, Bouchaud-Chabot A, Chabroux A, Toussirot E, Bardin T, Michel F.(4)

5. Swollen lymph nodes
Swollen lymph nodes is a result of acute infection with Borrelia burgdorferi, due to hybridomas generated from regional lymph nodes during acute infection showed reactivity against a small number of recombinant Borrelia-antigens, according to "Lymphoadenopathy during lyme borreliosis is caused by spirochete migration-induced specific B cell activation" by Tunev SS, Hastey CJ, Hodzic E, Feng S, Barthold SW, Baumgarth N.(5)

6. Etc.

B. Stage II: The second stage of Lyme disease, if it is left untreated
1. Lyme arthritis
"Lyme arthritis occurs when the spirochete, the bacteria that causes the disease, invades the joints and causes inflammation to the tissue that lines the joints," he said. "If left untreated, this inflammatory response can cause the cartilage within the joints to become damaged." according to "Effective Treatment of Lyme Disease-Related Arthritis Depends on Proper Diagnosis" posted in AAOS: American Academy of Orthopaedic Surgeons® / American Association of Orthopaedic Surgeons®(6)

2. Neurological disorders
Patient in the second stage of Lyme disease may be experience certain neurological symptoms many months or years after the initial infection, such as encephalomyelitis, epileptic crises, cognitive impairment, peripheral neuropathy and psychiatric disturbances such as depression, anxiety, panic attacks, catatonia, psychosis etc. Some patient continue to experience symptoms of fatigue, insomnia or psychiatric disorder in the post borrelia syndrome, according to " Tremor, seizures and psychosis as presenting symptoms in a patient with chronic lyme neuroborreliosis (LNB)" by Markeljević J, Sarac H, Rados M.(7)

3. Multiple erythema migrans
Patient with initial skin rash after bitten by tick and left untreated erythema migrans, up to 39 days after the onset of skin rash may experience with solitary and multiple erythema migrans, according to "Borrelia burgdorferi sensu lato bacteremia in Slovenian children with solitary and multiple erythema migrans" by Arnež M, Ružić-Sabljić E.(8)

4. Dizziness, palpitations and shortness of breath
Untreated of bitten by tick may result in atrioventricular (AV) block. In the report of Verbunt RJ, Visser RF, the scientist reported that a 40-year-old man was referred to the cardiology outpatient clinic with dizziness, palpitations and shortness of breath. He remembered being bitten by a tick two to three years previously, but had not noticed a characteristic skin rash. The ECG showed a prominent first degree atrioventricular (AV) block and ambulatory electrocardiographic monitoring showed an intermittent complete AV block. A definitive pacemaker was implanted. Antibodies to Borrelia were found, according to "[Total atrioventricular block following a tick bite].[Article in Dutch]" posted in PubMed (9)

5. Extreme fatigue and general weakness
As a result of prolonged period of infection as the bacteria has spread throughout the body.

6. Etc.

C. Stage 3
If the disease left untreated or with out noticing by the patient after bitten by a tick may last months to years. It can lead to recurring arthritis and neurological problems.
1. Chronic and recurring arthritis
As a result of a hierarchy of shared somatic mutations between members of a given clone. Intraclonal diversity among plasma cells of close physical proximity points toward an ongoing process of diversification and affinity maturation, possibly driven by the chronic presence of an autoantigen, according to "In situ diversification of the antibody repertoire in chronic Lyme arthritis synovium" by Ghosh S, Steere AC, Stollar BD, Huber BT.(9)

2. Neurological problems
May be due to Cerebral metabolic changes with the frequent presence of present of various neurological symptoms. In the study of 23 patients with lyme disease, researchers found that hypometabolism was precented in the temporal lobes in 17/23 (74%) patients. Of these, 12 had bilateral temporal lobe hypometabolism, two had left temporal lobe, and three had right temporal lobe hypometabolism. Seven of the patients with temporal lobe hypometabolism had diffuse cortical hypometabolism that included the frontal and parietal lobes. Lyme disease appears to have two primary patterns of brain involvement on FDG PET scans, specific temporal lobe hypometabolism or a diffuse cortical hypometabolism, according to "Cerebral metabolic changes associated with Lyme disease" by Newberg A, Hassan A, Alavi A.(10)

3. Etc.

II. Complications
Beside the most of common arthritic and neurological complications, here are some uncommon complications.
1. Non-Hodgkin lymphoma
Scientists found that persons who did not recall Borrelia infection yet tested positive for anti-Borrelia antibodies (OR = 4.2 [2.0-8.9]) are association between B. burgdorferi infection and risk of mantle cell lymphoma, according to "Borrelia infection and risk of non-Hodgkin lymphoma" by Schöllkopf C, Melbye M, Munksgaard L, Smedby KE, Rostgaard K, Glimelius B, Chang ET, Roos G, Hansen M, Adami HO, Hjalgrim H.(11)

2. Retrobulbar optic neuritis
Retrobulbar optic neuritis is a condition of vision disorder as a result of inflammation of the optic nerve, causing nerve damage that occurs in the section of the optic nerve located behind the eyeball. Although, relationship between RON and Lyme disease remains controversial, but there is a report that Lyme disease can cause vision disorder complication, according to "Retrobulbar optic neuritis: a complication of Lyme disease?" by E Krim, D Guehl, P Burbaud, A Lagueny(12)

3. Diaphragmatic paralysis and respiratory failure
There are some recorded cases of diaphragmatic paralysis as a complication of Neuroborreliosi, which is a disorder of the central nervous system caused by infection with a spirochete of the genus Borrelia and in one special case, scientists also reported that a 59 year old female presented with a recent history of abdominal pain and falls because of a weakness in her right leg. She had been complaining of flu-like symptoms with twitches in her back and pain in her right side for a month.Oon day 3 of admission she became increasingly short of breath and on examination had decreased bibasal air entry. On day 4 her respiratory rate was 25/min and arterial blood gases (ABG) demonstrated hypoxaemia but adequate ventilation with pH 7.51, Po₂ 6.7 kPa, and Pco₂ 4.7 kPa. Her chest radiograph showed left basal changes. On day 5 her Pco₂ had risen to 6.8; she was admitted to the intensive care unit and non-invasive ventilatory support was commenced. She had a decreased inspiratory pressure and a decreased vital capacity, according to "Diaphragmatic paralysis and respiratory failure as a complication of Lyme disease" by R A Abbott,, S Hammans,, M Margarson,, B M Aji(13)

4. Neurobrucellosis
Neurobrucellosis is a rare neurological complication associated with brucellosis, leading to symptoms of Headache, fever, fatigue, drowsiness and neck stiffness were the common clinical features. Cerebrospinal fluid (CSF) showed pleocytosis in 100%, elevated protein levels in 89% and low glucose level in 47% of the patients, according to "Short-course treatment in neurobrucellosis: a study in Iran" by Asadipooya K, Dehghanian A, Omrani GH, Abbasi F.(14)

5. Acute brachial diplegia
Acute brachial diplegia is generally defined as condition caused by bilateral supratentorial brain lesions of the prerolandic cortical and subcortical area. In some rear cases, acute brachial diplegia is a rare manifestation of acute Lyme infection and responds promptly to antibiotic therapy, according to "Acute brachial diplegia due to Lyme disease" by Gorson KC, Kolb DA, Marks DS, Hayes MT, Baquis GD.(5)

6. Endometriosis
Scientists at University of Crete, Heraklion report there are evidences which links endometriosis as a complication of Lyme disease by investigatiing he medical files of 405 women with endometriosis and 200 without endometriosis were studied retrospectively. We report 3 cases with endometriosis and Lyme disease. Of 405 patients with endometriosis treated in our study over a 6-year period, 3(0.8%) had Lyme disease, according to "Endometriosis-associated Lyme disease" by Matalliotakis IM, Cakmak H, Ziogos MD, Kalogeraki A, Kappou D, Arici A.(16)

7. Haematological complications
It is defined as a condition of blood related diseases, such as agranulocytosis/ granulocytopaenia, thrombotic trombocytopenic purpura and rarely aplastic anaemia. In the report in the study of a 55-year-old male with aplastic anaemia which developed after 45 days of the therapy with 200 mg ticlopidine to prevent coronary thrombosis. The treatment with ticlopidine was withdrawn and broad spectrum antibiotics as well as transfusion of packed red cells, platelets and G-CSF were administered. Two weeks after the onset of the disease, the number of white blood cells dropped to 0.5 x 10(9)/l, along with drop of both haemoglobin concentration and the number of platelets. At that time, weakness of facial muscles due to bilateral facial nerve paralysis with Bell's phenomenon and after that weakness of muscles of both legs and signs of polyradiculoneuritis were developed. Western blot analysis of blood and liquor showed a high concentration of IgG and IgM antibodies against Borrelia burgdorferi, according to "[Neuroborreliosis in patient with aplastic anaemia secondary to therapy with ticlopidine].[Article in Serbian]" by Colović N, Bumbasirević L, Palibrk V, Vidović A, Colović M.(17)

8. Recurrent laryngeal nerve paralysis
Although, recurrent laryngeal nerve paralysis is an extremely rare complication of neuroborreliosis associated with Lyme disease, but there is a report that 15-year-old girl referred with hoarseness and soft voice as a result of recurrent laryngeal nerve paralysis due to subclinical Lyme borreliosis, according to "Recurrent laryngeal nerve paralysis due to subclinical Lyme borreliosis" by Karosi T, Rácz T, Szekanecz E, Tóth A, Sziklai I.(18)

9. Pregnancy loss
During the investigation of Lyme disease: association with tissue invasion and spirochete persistence.at University of Utah School of Medicine, researchers said "Invasion of maternal uterine tissue, but not direct invasion of fetal tissue, is associated with low levels of pregnancy loss in mice infected during gestation, consistent with the detrimental effect of inflammatory cytokines on pregnancy"(22)

IV. Causes
Please read the definition above

V. Diagnosis
Diagnosis of Lyme disease is based on symptoms as indicated in the symptoms section and the geographic location. If you have any or combination of symptoms or complications above, after being bitten by a tick.
1. Serology testing
It is a study of blood serum and other bodily fluids to determine the immunity against different infecting organisms via the dosage of IgG. and may provide valuable information in patients with Western blot(c) and Enzyme-linked immunosorbent assay ELISA(d). Although, the test may not be accurate in the early stage of the disease, it can be helpful in the last 2 stages of Lyme disease. But in two-tiered antibody testing in Enzyme-linked immunosorbent assay ELISA,
The 2-EIA algorithm in early LD had similar sensitivity as C6 testing alone, and both strategies had better sensitivity than did standard 2-tiered testing (61% and 64%, respectively, vs 48%; P = .03 and P = .008). For late disease, all 3 strategies had 100% sensitivity. The specificity of the 2-EIA algorithm was equal to that of standard 2-tiered testing, and both 2-tiered strategies were more specific than C6 testing alone (for both, 99.5% vs 98.4%; P = .01). The positive predictive value of the 2-EIA algorithm was 70%, compared with 66% for standard 2-tiered testing and 43% for the C6 EIA alone. The 2-EIA strategy matched the individual strengths of the C6 EIA and Western blotting, without the drawbacks. The 2 EIAs provided sensitivity comparable to that of the C6 EIA but maintained the specificity of standard 2-tiered testing, according to "Two-tiered antibody testing for Lyme disease with use of 2 enzyme immunoassays, a whole-cell sonicate enzyme immunoassay followed by a VlsE C6 peptide enzyme immunoassay" by Branda JA, Linskey K, Kim YA, Steere AC, Ferraro MJ.(f)

2. Urine antigen tests
The test of antigens in the urine of the patient with suspect of Lyme disease may have some draw back because of the low concentration below the detection limit of clinical immunoassays. But with Hydrogel microparticles functionalized with high affinity baits can dramatically increase the sensitivity of urinary antigen tests for infectious diseases, according to "The use of hydrogel microparticles to sequester and concentrate bacterial antigens in a urine test for Lyme disease" by Douglas TA, Tamburro D, Fredolini C, Espina BH, Lepene BS, Ilag L, Espina V, Petricoin EF 3rd, Liotta LA, Luchini A.(g)

3. PCR tests on urine
The Polymerase Chain Reaction (PCR) technique test on Urine, has some application limits therefore suggesting the evaluation of the sensibility (SE), specificity (SP), predictive positive value (PPV) and predictive negative value (NPV) of a PCR test detecting a target sequence of OspA gene of Borrelia burgdorferi sensu lato, according to "[Reliability of a polymerase chain reaction (PCR) technique in the diagnosis of Lyme borreliosis].[Article in Italian]" by Grignolo MC, Buffrini L, Monteforte P, Rovetta G.(h)

4. Etc.

VI. How to prevent
A. Externally, What precautions should you take to avoid Lyme disease?
In areas where ticks are found, people should know about the risk of Lyme disease and protect themselves.
1. Find out from the local public health office if there are ticks, especially blacklegged ticks, in the area.
2. When walking in tick-infested areas, wear clothing that will keep ticks from getting to bare skin. Wear closed shoes, long-sleeved shirts that fit tightly around the wrist and tuck them into pants. Protect your legs by tucking pants into socks or boots. Ticks show up better on light-colored clothing.
3. Insect repellents containing DEET are safe and can effectively repel ticks. Repellents can be applied to clothing as well as exposed skin but should not be applied to skin underneath clothing (note: DEET may damage some materials). Always read and follow label directions.
4. Check for ticks on clothing and skin after being in tick-infested areas. A daily total-body inspection and prompt removal of attached ticks (within 18 to 24 hours) can reduce the risk of infection. Blacklegged ticks are very small, particularly the younger stages, so look carefully. Do not forget to check children and pets as well.
5. Carefully remove attached ticks using tweezers. Grasp the tick's head and mouth parts as close to the skin as possible and pull slowly until the tick is removed. Do not twist or rotate the tick and try not to squash or crush the tick during removal.
6. After removing ticks, wash the bite site with soap and water or disinfect it with alcohol or household antiseptic. Note the day of the tick bite and try to save the tick in an empty pill vial or doubled zip-lock bag.
7. Contact a doctor immediately if you develop symptoms of Lyme disease, especially when you have been in an area where blacklegged ticks are found. If you have saved the tick, take it with you to the doctor's office. Source from the "Lyme Disease Fact Sheet " from the Public health Agency of Canada(19)

B. Internally
Although there is no specific Lyme disease diet, health diet with different types of antioxidant and healthy living style should be helpful in preventing Lyme disease as antioxidants have proven to be effective in fighting against foreign invasion, including bacteria and virus Source from all about antioxidants (20). Researchers at the The University of Texas at San Antonio indicated that superoxide dismutase A(SodA) plays an important role in combating oxidative stress and is essential for the colonization and dissemination of B. burgdorferi in the murine model of Lyme disease.(21)

VII. Treatments
A. In conventional medicine perspective
Lyme disease is defined as an infectious disease and primary is treated by antibiotics and doses are depending to the stages of the infection. Researchers at the Boston University School of Medicine, Boston Medical Center, indicated that some patients have persistence of profound fatigue, myalgias, arthralgias without arthritis, dysesthesia/paresthesia, and mood and memory disturbances after standard courses of antibiotic treatment for Lyme disease. This constellation of symptoms has been variously referred to as "chronic Lyme disease," "post-Lyme disease syndrome," and "post-treatment chronic Lyme disease." Persistent symptoms have been reported in patients who are seropositive for IgG antibodies against Borrelia burgdorferi as well as in patients who are seronegative.
According to the Infectious Diseases Society of America (IDSA) guidelines, the antibiotics of choice are
1. Doxycycline (in adults)
a. Doxycycline is a member of the tetracycline antibiotics, used commonly to treat a variety of infections. In the study conducted by Tulane National Primate Research Center, Tulane University for the antimicrobial function of Doxycycline, could exert control over the inflammation elicited by Borrelia burgdorferi, found that antibiotics significantly reduced the production of tumor necrosis factor-alpha, interleukin (IL)-6, and IL-8 in a dose-dependent manner in all cell types. Microarray analyses of the effect of doxycycline on gene transcription in spirochete-stimulated monocytes revealed that the NFKB and CHUK (alias, IKKA) genes were down-regulated.(37)
Also number of studies showed that ceftriaxone and doxycycline are the 2 most efficient antibiotics, particularly in Lyme arthritis and in neuroborreliosis. In late Lyme borreliosis, these antibiotics are less efficient, and different treatment schemes with variations in dosage or duration did not produce convincing results(38)
b. Side Effects
Most common side effects includes
b.1. Digestive disorders such as nausea, diarrhea, vomiting, indigestion and heartburn
b.2. Reaction to sunlight (photosensitivity)
b.3. Loss of appetite
b.4. Etc.

2. Amoxicillin (in children)
a. Amoxicillin is a β-lactam antibiotic used to treat bacterial infections in children, but for For children who are unable to tolerate amoxicillin, there is currently no proven alternative oral therapy for LD. In a randomized, unblinded study compared 2 dosage regimens of cefuroxime axetil (20 mg/kg/d and 30 mg/kg/d) with amoxicillin (50 mg/kg/d), each given for 20 days, indicated that Children were enrolled if they were 6 months to 12 years of age, had erythema migrans, and met other eligibility requirements. Serologic testing occurred at entry and after 6 months. Follow-up evaluations for safety, tolerability, and efficacy occurred at 10 and 20 days, 6 months, and 1 year. Forty-three children were randomized (13 in the amoxicillin group, 15 in each cefuroxime axetil group); 39 completed 12 months of follow-up. At the completion of treatment, there was total resolution of erythema migrans in 67% of the amoxicillin group, 92% of the low-dose cefuroxime group, and 87% of the high-dose cefuroxime group, and resolution of constitutional symptoms occurred in 100%, 69%, and 87%, respectively. All patients had a good outcome, with no long-term problems associated with LD. One patient, who was well at the first 2 follow-up visits, was treated with doxycycline because of new constitutional symptoms(39)

b. Side effects of Amoxicillin is not limited to
b.1. Nausea, diarrhea, vomiting, rashes
b.2. Antibiotic-associated colitis
b.3. Etc.

3. Erythromycin (for pregnant women)
a. Erythromycin is an antimicrobial medicine similar to those of penicillin, and is often used for people who have an allergy to penicillins. The aims of the medicine is to provide an aggressive antibiotic treatment of the mother during pregnancy in preventing infection of the newborn.(40)
b. Side Effects
Side effects of the medicine is not limited to
b.1. Mild diarrhea, nausea, stomach discomfort, vomiting
b.2. Loss of appetite
b.3. Erythromycin can interact with other medicine, including simvastatin (Zocor), lovastatin (Mevacor), or atorvastatin
b.4. Etc.

4. Ceftriaxone
a. Ceftriaxone is a third-generation cephalosporin antibiotic used commonly against Gram-positive and Gram-negative bacteria. In a prospective, open label, randomized, multi-center study, a 14 day course of ceftriaxone was compared to 28 days of therapy conducted by New York Medical College, indicated that Ceftriaxone for 14 days eradicated the signs and symptoms of late Lyme disease in the majority of evaluable patients. Although there were more failures in the 14-day group than in the 28-day group, this study did not have the power to determine if a clinical subset of patients may benefit from 28 days of therapy.(41)
b. Side Efects is not limited to
b.1. Hypoprothrombinaemia and bleeding
b.2. Diarrhea, moderate pain, swelling, or redness at the injection site, nausea, vomiting.
b.3. Etc.

Despite numeral efforts and treatment with antibiotics, there is increasing evidence that some patients with the bacterial infection Lyme borreliosis (LB) have symptoms that persist for years afterwards such as symptoms of fatigue, musculoskeletal pain, and neurocognitive difficulties1 are attributed to a post-LB syndrome, also known as posttreatment chronic Lyme disease(42)

B. In Nutrition and Supplements perspective
Nutrition and supplements are always important during treatment of Lyme disease
1. Probiotics
It is very important for a patient with Lyme disease with antibiotics treatment as the medicine kills not only the infectious Borrelia, but also the good bacteria as well.

2. Antioxidants
All vitamins, supplements, phytochemicals of which can enhance the immune system in fighting against the forming of free radicals and raise the antioxidants will do

3. Co Q10
Co Q10 has played an important role in oxidative phosphorylation and has membrane stabilizing activity as it in oral form to treat various cardiovascular disorders including angina pectoris, hypertension, and congestive heart failure.(23)

4. Magnesium
Magnesium is essentail to keep muscle and nerve functioning normal and heart beat rhythmic. It also helps to support a healthy immune system, raises energy and enhances cognitive function.

5. Omega-3 polyunsaturated fatty acids (n-3 PUFAs)
Recent study showed that n-3 PUFAs display neuroprotective properties and exert beneficial effects on the cognitive function with aging. The brain's need of n-3 PUFAs is predominantly met by the blood delivery due to their limited synthesis in the brain. The present review focuses on the metabolism of n-3 PUFAs in the brain, including their accumulation and turnover(24)

6. NT factor
NT-Factor is a nutrient compound composed of phosphoglycolipids with with pre- and pro-biotics. The nutrient beside balances the health micro flora but also address the mitochondrial damage, reduce fatigue and cognitive dysfunction.

7. Etc.

C. In herbal medicine perspective
Since it is an emerging infectious disease, there is not much information about the use of herbal medicine in treating the disease, but herbalists view Lyme disease as a condition of overwhelming accumulation of toxins in the body as the result of the aggressive bacteria. Therefore detoxification of the organs and system toxins will bring the body back to harmonization.
1. The lymphatic system
The lymphatic system beside helps to regulate the body fluid but also perform essential functions including the removal of waste products from cellular metabolism. The proper function of the lymphatic system is vital for enhancing the immune system performance.
1. Cleavers
In the investigation of the phytochemical compounds in Galium aparine with various column chromatographic techniques in 95% ethanol extract of the plant, identified 1-(4-hydroxyphenyl)-ethanone (1), vanillic acid (2), 3,4-dihydroxybenzoic acid (3), p-hydroxycinnamic acid (4), gallic acid (5), 4-hydroxytruxillic acid (6). according to the study of "[Phenolic compounds from Galium aparine var. tenerum].

[Article in Chinese]" by Yang J, Cai X, Mu S, Yang X.(25)

2. Echinacea
a. Immune modulator
In the observation of ethanolic extract of fresh Echinacea purpurea and the changes in cytokine production in blood samples from 30 volunteers before and during 8-day oral administration found that Echinaforce regulates the production of chemokines and cytokines according to current immune status, such as responsiveness to exogenous stimuli, susceptibility to viral infection and exposure to stress, according to the study of "Effects of Echinaforce® treatment on ex vivo-stimulated blood cells" by Ritchie MR, Gertsch J, Klein P, Schoop R.(26)

b. Anxiety
In the evaluation of five different extract from Echinacea preparationsand it effects on anxiety found that three of these decreased anxiety but two of them had a very narrow effective dose range. Only one extract decreased anxiety within a wide dose-range (3-8 mg/kg). Anxiolytic effects were consistently seen in three different tests of anxiety, the elevated plus-maze, social interaction and shock-induced social avoidance tests. No locomotor suppressant effects were seen at any dose, according to "The effect of Echinacea preparations in three laboratory tests of anxiety: comparison with chlordiazepoxide" by Haller J, Hohmann J, Freund TF.(27)

c. Anti-viral properties
In the analyzing the extract from Enchinanea and its anti viral effect found that the extract interferes with the viral entry into cells. In sequential passage studies under treatment in cell culture with the H5N1 virus no EF-resistant variants emerged,according to "Anti-viral properties and mode of action of standardized Echinacea purpurea extract against highly pathogenic avian influenza virus (H5N1, H7N7) and swine-origin H1N1 (S-OIV)" by Pleschka S, Stein M, Schoop R, Hudson JB.(28)

3. Cat's claw
a. Anti-inflammatory and antioxidant activities
Oral extract of Cat's claw has demonstrated the activity of protection against indomethacin-induced gastritis, and prevention of TNFalpha mRNA expression and apoptosis, according to the study of `Anti-inflammatory and antioxidant activities of cat's claw (Uncaria tomentosa and Uncaria guianensis) are independent of their alkaloid content`by Sandoval M, Okuhama NN, Zhang XJ, Condezo LA, Lao J, Angeles' FM, Musah RA, Bobrowski P, Miller MJ.(29)

b. Antimicrobial activity
Cat`s claw has exerted antimicrobial activity against microorganisms frequently found in infected root-filled teeth, including Enterococcus faecalis, Staphylococcus aureus, and Candida albicans, according to the study of `In vitro antimicrobial activity of phytotherapic Uncaria tomentosa against endodontic pathogens`by Herrera DR, Tay LY, Rezende EC, Kozlowski VA Jr, Santos EB(30)

4. Etc.

2. Liver detoxification (31)
a. Milk thistle
Milk thistle, a flower plant of the daisy family have been traditionally claimed in treating chronic liver disease. It contains silymarin that helps to protect liver function and the liver in expelling toxins.

b. Licorice
Licorice is a legume plant and and native to southern Europe and parts of Asia. It contains glycyrrhizin that not only has both estrogenic and anti-estrogenic activity but also is an important liver herb with strong hepatoprotectant properties in treating the suppression of hepatic stellate cell activation and subsequent liver fibrosis.

c. Tabebuia heptaphylla
Tabebuia heptaphylla is also known as pink trumpet tree. It contains alkaloids, flavonoids, sulfur and essential oils helping to support the immune system, and it also has antifungal, antibacterial and antibiotic properties. It is a powerful antioxidant that helps to cleanse toxins accumulated in the liver as well as protecting the forming of cancerous cells in the prostate.

d. Stilingia root
Stilinga root not only helps to strengthen the immune cells but also prevent and treating food allergies and eczema by stimulating the removal of toxins accumulation in the liver caused by long term eating of preservatives, canned foods, fast foods and excessive alcohol drinking.

e. Pricky ash
Pricky ash is also known as toothache tree. It has been used traditionally as a digestive aid, to strengthen the nervous system. It also is a tonic and stimulant herb for the liver and gallbladder.

f. St. John wort
St. John wort is also known as tipton weed or klamath weed. It has been used traditionally in treating depression. It contains different flavonoids and 3-O-coumaroylquinic acid that has anti-inflammation and antioxidant effects by stimulating the immune system in fighting allergies and liver protection from toxins.

g. Fennel
Fennel contains anethole, polymers and essential oil that helps the liver and pancreas in the metabolism of fats and sugars. It also helps to dissolve fat deposits of the body and restore damaged liver cells that cause jaundice, hepatitis and other liver disorders.

2. Kidney detoxification(32)
a. Dandelion leaf
Dandelion is a rich source of vitamins A, B complex, C, and D, as well as minerals such as iron, potassium, and zinc. Dandelion root has been used for centuries in traditional Chinese medicine in treating liver disease by stimulating the removal of liver toxins. Dandelion leaf on the other hand are used as a diuretic to stimulate the excretion of urine in removing the toxin accumulated in the kidney.

b. Echinacea
Commonly called purple coneflower. It contains a wide variety of chemicals that not only helps to strengthen the immune system but also stimulates the removal of toxins that causes kidney inflammation and infection.

c. Corn silk
Corn silks are the silky fibers that are found under the leaves and on top of an ear of corn. It contains flavonoids, essential oil and minerals that helps effectively in treating acute and chronic inflammation of the urinary system caused by toxins accumulated in the kidney.

d. Artichoke
Artichoke is a perennial thistle originating from southern Europe containing thiamin, riboflavin, niacin. These are antioxidants that besides helping strengthen our immune system, it also is used to treat kidney diseases and protein in the urine caused by toxins through poor diet for a prolonged period of time.

e. Golden rod
Golden rod is a yellow flowering plant in the family of Asteraceae. Golden rod has been used in traditional medicines as a kidney tonic, and treating urinary infections and stones. Golden rod juice also helps to cleanse of kidney and bladder caused by toxins and inflammation.

3. Skin detoxification(33)
a. Strawberry leaf
Strawberries come in endless varieties but all leaves of all strawberries contain healing tannins. It has also been used to aid in the treatment of anemia, eczema, jaundice and other skin problems caused by weakening of the liver.

b. Burdock root
Burdock has traditionally been used in treating chronic skin ailments such as eczema psoriasis, and dermatitis. It also helps to purify the bloodstream of toxins causing skin diseases.

c. Oats
Oats contain antioxidants such as IP-6, vitamin E, and zinc that is not only needed for a healthy heart and prostate gland but also help in rejuvenating our skin by fighting against inflammation in the skin caused by toxin accumulation or bacteria infection.

4. Colon detoxification(34)
a. Flax seed
Flax seed contains high amounts of omega 3 fatty acid, fiber and lignan that not only helps in controlling cholesterol in the blood stream and provides essential nutrition to our body, its fiber also helps to soften the stool and promote bowel movements for relief of constipation by removing all toxins accumulated in the colon.

b. Psyllium
Psyllium contains about 70% soluble fiber and 30% insoluble fiber. Besides having proven record in Chinese medicine in treating high levels of cholesterol, its fiber portion has been used to treat constipation by softening stools and easing bowel movements .

c. Bentonite
Bentonite is a natural clay that comes from volcanic ash. Taken internally, the adsorbent action of bentonite helps to eliminate and remove toxic material from the intestine.

d. Liquid clay
Liquid clay moves through our body and attaches to any bacteria, virus as well as toxins in our intestine and removes them out of our body as wastes resulting in improved intestinal regularity, easing chronic constipation and easing indigestion.

e. Buckthorn bark
Buckthorn bark is native to Europe and parts of western Asia. It contains anthraquinones that stimulate intestinal movement and also attracts more water to the intestines resulting in a softened stool and removing toxins accumulated in the intestine out as wastes.

f. Rhubarb root
Rhubarb root has been used in Chinese medicine in treating both constipation and diarrhea. Intake of rhubarb root helps to improve intestine tone, as well as remove toxins from the intestine.

g. Cascara sagrada
Cascara sagrada is known to tone the relaxed intestinal muscles in the digestive system. Intake of cascare sagrada helps promote the digestive process in people affected by disorders in the digestion as well as chronic constipation.

5. Lung detoxification(34)
a. Lotus Root Tea
Made from the root of the esteemed Asian water lily. It helps dissolve and eliminate mucus and lung congestion over time. Lotus root traditionally has been used to neutralize toxins accumulated in the lung as well as in treating other respiratory diseases such as asthma, tuberculosis, and coughing.

b. Platycodon Root
Platycodon has been used in Chinese medicine for over a century in treating abscesses,
respiratory disorders, and intestinal disorders.Study shows that platycodon roots not only help
to treat coughs due to purulent sputum and inflammation in the chest area but also removes toxins in the lung.

c. Wild Cherry Bark
Wild cherry bark traditionally has been used to treat irritable andpersistent cough of bronchitis,
and pertussis due to increased irritability of respiratory mucosa. Since it has antispasmodic
qualities, it has been used with other herbs to treat asthma andenhance relaxation as well as
removing toxins from the lung.

d. Mullein
Mullein contains coumarin and rotenone. It has a long history of being used as a medicine and
is an effective treatment for asthma and respiratory disorders. Mullein also helps in soothing
the mucous membranes, reducing inflammation and encouraging healthy fluid production in
the lungs.

e. Ephedra
Epphedra has been used  in Chinese medicine traditionally  for 5,000 years in treating asthma,
hay fever and the common cold. It also helps to support healthy sinus nasal lung and respiratory
function by removing toxins in the lung.

f. Elecampane
Elecampane is also called horse-heal. It has been used for treatment of shortness of breath and
helps to promote a strong lung. Elecampane is a wonderful lung tonic. Useful for asthma, and
soothing to the lining of the lungs

6. Blood detoxification
a. Raw sauerkraut
Sauerkraut is finely shredded cabbage and has been fermented by various lactic acid bacteria
with distinct sour flavor. It contains high amounts of  vitamin C, lactobacilli  and other nutrients
that helps to improve blood circulation and increase level of oxygen in the blood stream. It also
is said to have done a super job in purifying your blood as well as anti aging effects.

b. Garlic
Garlic is nature's super food. Besides having been used in strengthening the immune system,
fighting inflammation and infection caused by bacteria, virus, and chronic illness. It also is a
blood thinner, blood purifier as well as increasing the level of oxygen in the blood  and improving   blood  circulation.

c. Angelica root
Angelica root has been used in traditional Chinese medicine for thousand of years in improving
blood quality and purity, and help strengthen the immune system as it supports the body's
removal of toxins in the blood.

d. Red Clover Tops
Red clover tops traditionally has been used with other herbs  to support the quality of the
blood by increasing the level of oxygen circulation of blood to transport  nutrients to the cells
needs. It also is a liver tonic as well as maintaining healthy bowel function and supports
digestion. 

f. Burdock
Burdock, besides helping to cleanse our liver, it also contains substances that help to strengthen
our immune system as well as reducing inflammation caused by bacteria and virus.
Traditionally, burdock is very effective in providing the strength to clean and normalize the
blood stream.

g. Oregon Grape Root
Oregon Grape is a native plant on the North American west coast from British Columbia to
northern California. It's root contains  substances helping to decrease bacterial resistance to
antibiotics and antibacterial agents, as well as anti-inflammation. Oregon grape root is
described as one of  the best western herbs for supporting liver function. The  potent root  is also
recognized as a whole body cleanser and blood purifier. 

7. Etc.

D. In Traditional Chinese medicine perspective
Traditional Chinese medicine defined Lyme disease as a result of toxic fire caused by aggressive bacteria infection. Patient with toxic fire can be identified by examining the symptoms and physical appearance, such as early stage sores or carbuncles, red, painful, swollen,hot skin lesions, fever, mild chills, headache with Tongue thin coating, Pulse rapid forceful.
Traditional Chinese medicine herbal formulas Xian Fang Huo Ming Yin (Sublime Formula for Sustaining Life) main functions are to clear heat and relieve toxic fire while reducing swellings, promoting discharge of pus, invigorating the blood and alleviating pain.
1. Jin Yin Hua - 9g
Jin Yin Hua is also known as honey sucker flower. The sweet and cool herb has been used in TCM to treat respiratory tract infection, influenza, acute infection of the tonsils and the mammary glands, bacterial type of dysentery, etc. as it clears Heat, expels toxins, etc., by enhancing the functions of lung, heart, large intestine, and stomach channels.

2. Gan Cao (Licorice Root) - 3g
Gan Cao is also known as Licorice root. The sweet and neutral herb has been used in TCM as anti allergy, anti inflammation, anti ulcer, anti convulsion and to treat stomach weakness, tired and lack of strength, palpitation and short of breath, cough with abundance of phlegm, stomach and solar plexus pain, etc., as it tonifies the Spleen, benefits the Qi, moistens the Lungs, calms cough, deaf or acute pain, by enhancing all 12 channels.

3. Zhe Bei Mu - 3g
Zhe Bei Mu is also known as Fritillary Bulb, the slightly cold, sweet and bitter herb has been used in traditional Chinese medicine as antibiotic agent and to treat cough and get rid of phlegm, hot cough, etc, as it transforms Phlegm, relieve cough, clears Heat, dissolves nodules, etc., by enhancing the function of lung and heart channels.

4. Gua Lou 3g
Gua Lou or Gua Lou Gen or Tian Hua Fen, , is also known as trichosanthes root. The sweet, slightly bitter and cold herb has been used in TCM as anti HIV, anti tumor, anti bacteria, etc. agent and to enhance the immune system, promote abortion, lower blood sugar, etc., as it clears lung heat, dissolves phlegm, gets rid of toxicity, expels pus, etc., by enhancing the functions of lung and stomach channels.

5. Dang Gui - 6-12g
Dang Qui is also known as Angelica Root. The sweet, bitter, acrid and warm herb has been used in TCM to regulate the menses, lower lipids, reduce platelet coagulation and swelling, expel pus, relieve pain, etc/, as it tonifies and moves Blood, calms pain, moistens the Intestines, etc., by enhancing the function of heart, liver and spleen channels.

6. Chi Shao Yao - 3g
Chi Shao or Chi Shao Yao is also known as Red Peony Root, the bitter, sour and cool herb has been used in TCM to anti-spastic, antipyretic, anti-inflammatory, antibiotic, anticonvulsant, analgesic, sedative agnet and to lower blood pressure, dilate peripheral blood vessels, coronary arteries, treat viral hepatitis, chronic constipation, asthma, whooping coughs, diabetes, etc., as it clears Heat, cools Blood, eliminates Blood accumulation, calms paindilates, etc., by enhancing the functions of liver and spleen channels.

7. Ru Xiang 3g
Ru Xiang is also known as Frankincense Carterii, mastic. The bitter acrid and warm herb has been used in TCM to relieve pain due to blood clots, treat spastic muscle, carbuncles, gum bleeding, gingivitis, rheumatoid arthritis, cirrhosis of liver , etc., as it clears blood stasis, alleviates pain, resolves edema, promotes tissue regeneration, etc., by enhancing the functions of
heart, liver and spleen channels.

8. MoYao - 3g
Mo Yao is also known as Myrrha, It is exuded from the bark of a shrub of Abyssinia and Arabia, species Commiphora Myrrha, belonging the family Burseraceae. The bitter and neutral herb has been used in TCM as an antibiotic and to inhibits pain, reduces swelling and heal wound due to injuries, bruises, rheumatoid arthritis, tumors in the uterus, hemorrhoid by moving blood, relieving pain and promoting tissue regeneration as it enhances the function of liver, spleen, heart channels.

9. Fang Feng - 3g
Feng Fang is also known as Saposhniovia divaricate root. The sweet, warn and acrid herb has been used in TCM as antipyretic, antibiotoc, antiviral agent and to treat joint and muscle pain, blurry vision and headache, etanus, relieve pain, etc., as it expels Wind, releases the Exterior, disperses Dampness, calms pain, etc., by enhancing the functions of bladder, liver and spleen channels.

10. Bai Zhi - 3g
Bai Zhi is also known as angelica root. The acrid and warm herb has been used in TCM as Antipyretic agent and to relieves pain, stimulate CNS, respiratory system, increase blood pressure, slows heart rate, deepens breathing, etc., as it releases the exterior, expels Wind, dries Dampness, clear superficial swellings, etc., by enhancing the function of lung and stomach channels.

11. Chuan Shan Jia- 3g
Chuan Shan Jia is also known as Pangolin Scales. The salty, cool and tastless herb has been used in TCM to promote lactation, stop pain, pain in the joints of lower limbs, chronic malaria, rid of parasites, etc. as it moves Blood, resolves delayed menstruation and edema, promotes lactation, expels pus, etc, by enhancing the functions of liver and stomach channels.

12. Zao Jiao Ci - 3g
Zao Jaoi Zi is also known as Chinese Honeylocust Spine. The warm, acrid and slioghtly toxic herb has been used in TCM as antibiotic, anti-inflammation, anti virus, anti-allergy, anticoagulation, anti tumor agent and to regulate immune system, etc. as it expels toxins, promote circulation in channels, expel pus, invigorates Blood, etc., by enhancing the function of
liver and stomach channels.

13. Chen Pi 9g
Chen Pi is also known as Tangerine Peel, the bitter, acrid and warm herb has been used in Traditional Chinese medicine to improve digestion, stop vomiting, hiccups and bleeding increase blood pressure, stimulate blood vessels, regulate movement of uterus, as it regulate the movement of Qi, Middle burner, dries Dampness, transforms Phlegm, etc., by enhancing the functions of lung and spleen channels.
(35,36)

Author note: The article is for information and education purpose only, please consult with your doctor and the related field specialist before applying


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Attention Deficit Disorder (ADHD/ADD)

I. Attention Deficit Disorder (ADHD/ADD) also known as attention deficit hyperactivity disorder is a chronic disease occurs in certain age and years of a children, defined as a condition with characteristics of co-existence of attentional problems and hyperactivity. It effects about 5% of the all children in the world with boys have 3-4 times higher risk than girl. Over one third of children with ADHD will have continued symptoms existed into their adult life.

II. Classification
ADHD is classified with coexistence of Disruptive behavior disorder
Although any disorder can be co-existed with ADHD, disruptive behavior disorder is one of most common one, including
a. Oppositional defiant disorder
Oppositional defiant disorder is defined as a behavior of defiance and disobedience to the authority
b. Conduct disorder
Conduct disorder is defined as long-term (chronic) behavior problems, including Defiant or impulsive behavior such as aggression, destruction of property, stealing, etc.
c. Antisocial personality disorder
Antisocial personality disorder is defined as a characteristic of persistently disregard and violation of the rights of others, such as deceit, manipulation, etc.

III. Types of Attention Deficit Disorder (ADHD/ADD)
Attention Deficit Disorder (ADHD/ADD) is classified into 3 subtypes
A. Predominantly hyperactive-impulsive
1. Predominantly hyperactive-impulsive is defined as a condition in which a child has an unusually high activity level impulsively in a short period span. Children with the disorder usually have behavior and learning disabilities with (six or more) symptoms in the hyperactivity-impulsivity categories. Researchers found that Children with the disorder have high levels of cortisol.

2. Symptoms
2.1. Children who have symptoms of hyperactivity may:
a. Fidget and squirm in their seats
b. Talk nonstop
c. Dash around, touching or playing with anything and everything in sight
d. Have trouble sitting still during dinner, school, and story time
e. Be constantly in motion
f. Have difficulty doing quiet tasks or activities.
g. Sleep Complaints(I)

2.2. Children who have symptoms of impulsivity may:
a. Be very impatient
b. Blurt out inappropriate comments, show their emotions without restraint, and act without regard for consequences
c. Have difficulty waiting for things they want or waiting their turns in games
d. Often interrupt conversations or others' activities.

B. Predominantly inattentive
1. Predominantly inattentive is defined as a condition of a child with serious inattention problems, as they do cause any problem with others, but sit quiet and ignore others with six or more symptoms in the inattention category. Researchers found that Children with the disorder have Low levels of cortisol.
2. Symptoms
a. Be easily distracted, miss details, forget things, and frequently switch from one activity to another
b. Have difficulty focusing on one thing
c. Become bored with a task after only a few minutes, unless they are doing something enjoyable
d. Have difficulty focusing attention on organizing and completing a task or learning something new
e. Have trouble completing or turning in homework assignments, often losing things (e.g., pencils, toys, assignments) needed to complete tasks or activities
f. Not seem to listen when spoken to
g. Daydream, become easily confused, and move slowly
h. Have difficulty processing information as quickly and accurately as others
i. Struggle to follow instructions(1)

3. Combined hyperactive-impulsive and inattentive
This a combined subtypes of ADHD with Six or more symptoms of inattention and six or more symptoms of hyperactivity-impulsivity. Researchers found that children with the disorder have abnormal levels of cortisol.

IV. Causes
1. Heredity
ADHD can be an inherited form the parent as a result of abnormal genes, according to the study of "Quantitative and Molecular Genetics of ADHD" by Asherson P, Gurling H., researchers indicated that there is consistent evidence of monoamine neurotransmitter involvement with the best evidence coming from genetic markers in or near the dopamine D4 and D5 receptor genes. Recent genome-wide association studies have identified new association findings, including genes involved in cell division, cell adhesion, neuronal migration, and neuronal plasticity(2)

2. Perinatal factors
Perinatal factors such as miscarriage symptoms, premature delivery symptoms, severe flu attacks (cold with fever, without virus confirmation), tobacco abuse, alcohol abuse (to become drunk), minor congenital malformations, neonatal seizures and hospitalizations may cause ADHD to the new born, according to the study of "[Perinatal factors associated with attention deficit/hyperactivity diagnosis in Colombian Paisa children].[Article in Spanish]" by Pineda DA, Puerta IC, Merchán V, Arango CP, Galvis AY, Velásquez B, Gómez M, Builes A, Zapata M, Montoya P, Martínez J, Salazar EO, Lopera F., posted in PubMed(3)

3. Heavy prenatal maternal smoking
Exposure to heavy maternal cigarette smoking in pregnancy and severe maternal psychosocial stress during pregnancy increase risk of ADHD as a result of neuropsychological deficits commonly seen in ADHD, according to the study of "Adverse effects of heavy prenatal maternal smoking on attentional control in children with ADHD" by Motlagh MG, Sukhodolsky DG, Landeros-Weisenberger A, Katsovich L, Thompson N, Scahill L, King RA, Peterson BS, Schultz RT, Leckman JF., posted in PubMed(4)

4. Environmental influences
In a study of 200 children with ADHD (149 males and 51 females) and 286 healthy controls (135 males and 151 females). The ADHD DSM-IV diagnosis was obtained using the DICA and BASC evaluation instruments, and the children's mothers or grandmothers filled out a questionnaire on each child's exposure to prenatal, neonatal, and early childhood risk factors, conducted by
University of San Buenaventura, researchers indicated that the risk of developing ADHD must include these environmental factors as covariates(5)

5. Brain injure
The behavioural and cognitive sequelae of traumatic brain injury (TBI) have features in common with attention deficit/hyperactivity disorder (ADHD), according to the study of "Inhibitory control in children with traumatic brain injury (TBI) and children with attention deficit/hyperactivity disorder (ADHD)" by Konrad K, Gauggel S, Manz A, Schöll M., PubMed(6)

6. Refined Sugar
In the study of A total of 107 students participated, and eight boys and one girl (8.4% of the total) categorized as high risk for ADHD according to diagnostic criteria, conducted by Graduate School of Education, Dankook University, posted in PubMed(7), researchers indicated that children who consumed less sugar from fruit snacks or whose vitamin C intake was less than RI was at increased risks for ADHD (P < 0.05). However, no significant association was observed between total volume of simple sugar intake from snacks and ADHD development.

7. Artificial food additives and dyes
Although there is contradictive results of how Artificial food additives causes of ADHD, Some reserachers do believe that the balance of existing evidence neither refutes nor supports the link between AFCs and ADHD, which highlights the need for carefully designed studies to further investigate the link between AFCs and ADHD, according to the study of "A research model for investigating the effects of artificial food colorings on children with ADHD" by Kleinman RE, Brown RT, Cutter GR, Dupaul GJ, Clydesdale FM., posted in PubMed(8)

8. Toxic Substances
Toxic substances may be considered as a substantial contribution to the etiology of ADHD, as a result of affecting the dopamine system, according to the study of "Etiologic subtypes of attention-deficit/hyperactivity disorder: brain imaging, molecular genetic and environmental factors and the dopamine hypothesis" by Swanson JM, Kinsbourne M, Nigg J, Lanphear B, Stefanatos GA, Volkow N, Taylor E, Casey BJ, Castellanos FX, Wadhwa PD., posted in PubMed(9)

9. Maternal stress during pregnancy
Maternal stress during pregnancy may increase the risk of the development of ADHD symptomatology after controlling for family history of ADHD and other environmental factors(36)

10. Etc.

V. Diseases with similar symptoms to ADHD
A number of other conditions and disorders have similar symptoms, therefore, it is imporant for the doctors to rule out before treating ADHD
1. Visual disturbances
Visual disturbances are defined as a condition of abnormalities of sight associated with neurological disorders often include double vision (diplopia), moving or blurred vision as a result of nystagmus, a rapid involuntary movements of the eyes. Some children with ADHD are experience the symptoms of visual disturbances as a result of neuropsychological dysfunction.

2. Thyroid disorders
Children who are experience the symptoms of dementia and depression, dysfunction of cerebellum and cranial nerves as a result of hypothyroidism (lacks sufficient thyroid hormone) may be risk of misdiagnosis as the symptoms are similar of those in ADHD (10)

3. Epilepsy
Epilepsy is defined as condition of chronic neurological disorders characterized by seizures and with recurrent symptoms as a result of mutations in several genes. ADHD occurs frequently in children with epilepsy. The factors associated with increased risk of ADHD include the onset age of epilepsy, the types of seizures or epileptic syndromes, the epileptiform EEG discharges, and the effects of antiepileptic drugs(11)

4. Sleeping problems, and attention-deficit/hyperactivity disorder.
Some children with ADHD may be experience the symptoms of childhood eczema, sleeping problems, but not all of them. Researchers at University Clinic of Wuerzburg indicated that ADHD and AE appear to be strongly and independently associated in children with sleeping problems, but not in children without sleeping problems. A substantial part of diagnoses met for ADHD might be engendered by the presence of AE and concomitant sleeping problems.(12)

5. Some genetic disorders
Researchers at the Complejo Hospitalario Universitario de Albacete found that the X-chromosome-linked ichthyosis is caused by mutation or deletion of the STS gene as. Depending on its size, it can present as an isolated entity or combined with a syndrome caused by neighbouring genes, thus associating itself with other monogenic diseases as well as other mental disorders. The most relevant findings from the literature review are the importance of the Xp22.3-pter region and the higher incidence of neurological disorders among males such as attention deficit hyperactivity disorder, autism and X-linked mental retardation(13)

6. Eenuresis
Nocturnal enuresis (MNE) or bedwetting is defined as condition of involuntary urination while asleep inchildren at which bladder control usually occurs. Researchers at Duzce University School of Medicine said that monosymptomatic nocturnal enuresis (MNE) and attention deficit and hyperactivity disorder (ADHD) are multifactorial disorders and biological, social, and psychological factors may play significant roles in the development of both. Children with enuresis display a higher prevalence of ADHD compared to the normal population, in a study of A total of 64 children between the ages of 6 and 13 years (14)

7. Schizophrenic
Schizophrenia is defined as a serve mental disorder characterized by a breakdown of thought processes and by poor emotional responsiveness, including symtoms similar to those of ADHD.
and both associated with deficits in inhibition and working memory, but the hypothesis that working memory is a primary deficit in schizophrenia, but secondary to the inhibitory deficit in ADHD.(15)

8. Substance Use Disorders
In the replied to the article by Timothy E. Wilens, M.D. in The American Journal of Psychiatry, VOL. 164, No. 6, the writer wrote that the case presented does exhibit symptoms typical of marijuana users (4—6). According to Fletcher et al. (7), long-term cannabis use is associated with disruption of short-term memory, working memory, and attentional skills, all of which are exemplified in the case presented in Dr. Wilens’s article (16)

9. Autism and ADHD are characterized with the association of neurodeficits
Even though there are allots of similar symptom, but children with ASD also showed slower rates of adaptation compared with both control groups while children with ADHD did not show this excessive generalization to the proprioceptive target, but they did show excessive variability in the speed of movements with an increase in the exponential distribution of responses (τ) as compared with both TD children and children with ASD.(17)

10. Tourette's Syndrome
Tourette syndrome (TS) is defined as a neurological disorder characterized by repetitive, stereotyped, involuntary movements and vocalizations called tics. Some time it is misdiagnosis to children with ADHD or vice versa, but there are the evident that ADHD are more common in patient with chronic tics and Tourette's syndrome(18)

k. Oppositional Defiant Disorder (ODD)
ODD is a psychiatric disorder that is characterized as a set of symptoms, including aggressiveness and a purposefully bother and irritate others. ODD may sometime associate with ADHD and other neuropsychiatric disorders including, depression, Tourette's syndrome, etc..and sometime they can be treated with the same medication and at different improvement rate(19)

11. Anxiety Disorders
Anxiety disorder is defined as a condition of several different forms of a type of mental illness of abnormal and pathological fear.. In the study of children (8-17 years) with anxiety disorders (n = 24) and children (8-16 years) with ADHD (n = 23) on neurocognitive tests of both general and emotion-based attention processes, showed that children with ADHD demonstrated poorer selective and sustained attention, whereas youth with anxiety disorders demonstrated greater attentional bias toward threatening faces on a visual probe task.(20)

12. Depressive Disorders
Depressive disorders is defined as a metal illness of which includes mood, and thoughts of the patient, affecting their way of eating and sleeping, feeling, etc. with the prevalence rate for MDD is 6.7%, while the ADHD prevalence rate in US adults is 4.4%.(21)

13. Etc.

VI. What to avoid
It is important for parent and the benefits of the child avoided intake of food that promote the brain allergic reaction, impaired social and communication skill, limited interest, etc.
A. For Children
1. Sugar
Sugar may rob the body of vitamins, minerals, and enzymes and increases hyperactivity in ADHD as a result of fluctuation of sugar levels. Researchers found that excessive sugar intake may lead to alterations in mesolimbic dopamine signaling, which could contribute to the symptoms associated with ADHD. We recommend further studies to investigate the possible relationship between chronic sugar intake and ADHD.(28)

2. Artificial ingredients
a. Artificial colors

Food color is any substance added in to the food to preserve its favors or to simulate a natural state of the foods with an aim to make customers to buy them. Although, they have been tested by the government food body to ensure its safety, but unfortunately, it has interfered the neurological processes, such as the behavior, personality and learning ability of children with or without autism if taken in high dose.
It is said that some artificial ingredient such as FD & C Red No. 2 dye have shown to promote cancerous growth. Researcher found that removing the artificial colors from the autistic children diet, improve in attention deficit and hyperactivity behaviors dramatically.
b) Artificial flavors
Artificial flavors are any synthesized chemical added to manufactured foods to change or make its taste better such as banana - isoamyl acetate; cinnamon - ethyl cinnamate; orange - octyl acetate and pineapple - methyl butyrate; pear. It causes nervous tension including mental concentration, behavior, lost of energy and weakened immune response.
It is said that long-term usage can increase your risk of cancer, cardiovascular disease and other degenerative conditions to children's central nervous system.

c) Artificial preservatives
Artificial preservatives are a group of chemical substances, such as BHT, nitrates, sulfites, sulfur dioxide, BHA, etc. added to food, sprayed on the outside of food, or added to certain medications with the purpose of preventing food from spoiling or discoloring. It causes allergic reactions in children, resulting in skin rashes or facial swelling and worsening asthma.

d) Artificial Addictive
Artificial addictive is defined as substances, adding to foods from the manufacture with the purpose of preservation, coloring, texture and flavor. Studies found that artificial additive can causes several types of cancer and tumor. Many of them have negative impacts in children with ADHD.
i) Olestra
Olestra is a fat substitute used in crackers and potato chips. It is type of additive can not be absorbed by the digestive system, leading to diarrhea, loose stools, abdominal cramps.
ii) Monosodium glutamate (MSG)
MSG is used as a flavor enhancer in many cooking and preservative foods. It is said that MSG can cause sensitive neurons to die. leading to headache, nausea or vomiting.

e) Artificial sweeteners
Artificial sweeteners is a synthesis sugar substituted substance. It has been used increasingly in replacing natural sugar in a wide range of products traditionally containing sugar. Studies found that artificial sweetener may increase risk of bladder and brain cancers.
i) Sucralose
It is 600 times as sweet as sugar and has been used in beverages, frozen desserts, chewing gum, baked goods, etc. and belongs to a class of chemicals called organochlorides. Some of them are considered toxic to our health.
ii) Lead acetate
It is an artificial sugar substitute made from lead, it causes lead accumulated in the body, leading to nervous symptoms.
iii) Aspartame
It is 200 times as sweet as sugar and can be used as a tabletop sweetener, frozen desserts, gelatins, etc. Researchers found that aspartame may increase the risk of brain damage and cancer.(26)

3. Trans Fat
Trans fat has been proven to inhibit the function of nerve function as Diets high in fat, especially trans and saturated fats, adversely affect cognition, while those high in fruits, vegetables, cereals, and fish are associated with better cognitive function and lower risk of dementia(29). trans fat is the hydrogenated oil found in many commercial mayonnaise, margarine, and peanut butter etc. and can cause cholesterol building up in the arteries, leading to less blood circulation to the central nervous system.

4. Yeast extract
It is also known as processed yeast products and has been used as food additives or flavourings under the name of monosodium glutamate (MSG). It contains glutamic acid which is classified as exitotoxins, and can cause brain damage in some studies.

5. Casein
Casein is a protein found in milk and foods containing milk, such as cheese, butter, yogurt, etc. Studies found besides promoting cancer, it also increases the risk of bad cholesterol building up in the arteries, leading to heart diseases and stroke. Casein after intake can also be broken down to casomorphins, an chemical agent which is known to interfere with the function of neurotransmitter in transmitting information and decrease the immune response to foreign bacteria and virus invasion.

6. Non organic foods
Non organic foods may contain
i) Pesticides & Herbicides
Pesticides & Herbicides is highly toxic. Because of their value of increasing the production of foods and prevent insect eating away the profits of the growers, it have been widely uses in non organic farming. Intake of non organic foods may weakened the immune system as well as interfering the liver function in toxic elimination, leading to central nervous tension and exhibiting the symptoms of ADHD.
ii) Contaminated Sewage Sludge
The increasing uses of contaminated sewage sludge containing human waste, industrial waste and toxic chemicals as a fertilizer, causes crop contamination, leading to major chronic health problem, including increasing the severity of the nervous symptoms for children with ADHD.
iii) Hormones & Antibiotics
Animal fed with fed antibiotics, hormones, ground up remains of other animals causes hormone imbalance in our body, leading central nervous disorder, increasing the risk of irregular cell growth, and damaging the balance of beneficial bacteria in the intestines.

7. Refine products
Refined products with little fiber release sugar in the blood stream quickly, causing the responses of pancreas to produce high level of insulin to neutralize it in a short period of time, that interferes with the normal function of central nervous system in controlling the concentration, focus and behaviour for children with ADHD.

8. Etc.

B. During pregnancy
1. Alcohol

Moderate in take of alcohol can be helpful in enhancing the circulatory and nervous functions, but excessive intake of alcohol during pregnancy can increase the risk of low birth weight and birth defect including ADHD. In this prospective study of alcohol and other substance use during pregnancy, a cohort of 650 women was interviewed at each trimester of pregnancy demonstrated between prenatal maternal alcohol use and growth and morphologic abnormalities in the offspring. Low birth weight, decreased head circumference and length, and an increased rate of fetal alcohol effects were all found to be significantly correlated with exposure to alcohol during the first 2 months of the first trimester(34). Other sugested that alcohol consumption during pregnancy may associated to neuropsychological deficits of the offdpring, as Prenatal alcohol exposure may have its primary effect on brain growth, reflected by smaller forehead widths, and may suppress neural crest migration to the branchial arches, reflected by deficits in ear length and mandibular dimensions(35)

2. Drugs
It is not always possible to isolate the effect of marijuana exposure from other possible confounders on pregnancy outcome, but some studies suggested it might have subtle negative effects on neurobehavioural outcomes, including sleep disturbances, impaired visual problem solving, hyperactivity, impassivity, inattention, and increased delinquency.(32)

Other researchers point out that Prenatal marijuana use was significantly related to increased hyperactivity, impulsivity, and inattention symptoms as measured by the SNAP, increased delinquency as measured by the CBCL, and increased delinquency and externalizing problems as measured by the TRF. The pathway between prenatal marijuana exposure and delinquency was mediated by the effects of marijuana exposure on inattention symptoms. These findings indicate that prenatal marijuana exposure has an effect on child behavior problems at age 10.(33)

3. Smoking
Smoking during pregnancy cause the exposure of nicotine to the fetal neuroteratogen of which may lead to lower executive function proficiency, according to the Behavioral Rating Inventory of Executive Function(37)

4. Etc.

VII. Diet for ADHD
Diet can affect cognitive ability and behaviour in children and adolescents. Nutrient composition and meal pattern can exert immediate or long-term, beneficial or adverse effects. (40)
1. Black bean
a. Antioxidant effect
In the evaluation of the indigestible fraction (IF)of the cooked seeds of three pulses (black bean, chickpea and lentil) and their antioxidant effect found that Condensed tannins were retained to some extent in the IF that exhibited significant antioxidant capacity. The total IF of the three pulses produced short chain fatty acids (SCFA) after 24 h of in vitro fermentation by human colonic microflora. IF from black bean and lentil were best substrates for the fermentative production of butyric acid, according to "In vitro fermentability and antioxidant capacity of the indigestible fraction of cooked black beans (Phaseolus vulgaris L.), lentils (Lens culinaris L.) and chickpeas (Cicer arietinum L.)" by Hernández-Salazar M, Osorio-Diaz P, Loarca-Piña G, Reynoso-Camacho R, Tovar J, Bello-Pérez LA.(46)

b. Nervous system
Protein is essential for the brain in transmitting information between themselves and cells in the other parts of the body, thus reducing the blood sugar levels from rising too rapidly after a meal, reducing the risk of nervous symptoms cause of anxiety, stress and depression, etc., according to the study of "The planar polarity protein Scribble1 is essential for neuronal plasticity and brain function" by Moreau MM, Piguel N, Papouin T, Koehl M, Durand CM, Rubio ME, Loll F, Richard EM, Mazzocco C, Racca C, Oliet SH, Abrous DN, Montcouquiol M, Sans N.(47)

c. Tryptophan
Tryptophan is one of the 10 essential amino acids which the body uses to synthesize the proteins for brain cells need, thus enhancing the nerve cells in information transmitting between themselves and cells in the parts of the body that reduces the risk of anxiety and depression, according to the study of "The effects of tryptophan depletion on neural responses to emotional words in remitted depression" by Roiser JP, Levy J, Fromm SJ, Nugent AC, Talagala SL, Hasler G, Henn FA, Sahakian BJ, Drevets WC.(48)

2. Buckwheat
a. Antioxidant activity
in the investigation of buckwheat samples (Xingku No.2 and Diqing) grown at three locations were analyzed for free and bound phenolic content and its antioxidant effects found that additionally, growing conditions and the interaction between variety and environment may have more contribution than variety to individual phenolics and antioxidant properties of tartary buckwheat. Environmental parameters such as higher altitudes may also have an increasing effect on rutin and phenolic acids. according to "Phenolics content and antioxidant activity of tartary buckwheat from different locations" by Guo XD, Ma YJ, Parry J, Gao JM, Yu LL, Wang M.(49)

b. Anti-fatigue properties
In the evaluation of tartary buckwheat extracts (TBE) and its anti-fatigue effect found that tartary buckwheat extracts had anti-fatigue properties, which extended the exhaustive swimming time of mice, effectively inhibiting the increase of BLA, decreasing the level of BUN, increasing the tissue glycogen content and the activities of SOD and GPx of mice, according to "Anti-fatigue properties of tartary buckwheat extracts in mice" by Jin HM, Wei P.(50)

c. Tryptophan
Tryptophan is one of the 10 essential amino acids which the body uses to synthesize the proteins for brain cells need, thus enhancing the nerve cells in information transmitting between themselves and cells in the parts of the body that reduces the risk of anxiety and depression, according to the study of "The effects of tryptophan depletion on neural responses to emotional words in remitted depression" by Roiser JP, Levy J, Fromm SJ, Nugent AC, Talagala SL, Hasler G, Henn FA, Sahakian BJ, Drevets WC.(51)

3. Lentils
a. Omega 3 fatty acid
The omega 3 fatty not only helps to maintain the ratio of Omega 6 fatty acid that reduces the risk of over production of prostaglandin hormones (according to the study of "Effect of Clupeonella grimmi (anchovy/kilka) fish oil on dysmenorrhoea" by Moghadamnia AA, Mirhosseini N, Abadi MH, Omranirad A, Omidvar S.(52), it also helps to prevent of oxidation bad cholesterol (LDL), thus reducing the risk of free radical cause of cardiovascular disease, according to the study of "Fish oil for the treatment of cardiovascular disease" by Weitz D, Weintraub H, Fisher E, Schwartzbard AZ.(53)

b. Folate
Folate beside is important for the production of red blood cells, and for the proper development of the brain, it also helps to enhance the replication and maintain DNA and RNA, thus reducing the risk of birth defects, in a study of "Go folic!" by Bland J.(54) researchers state that in order to prevent neural tube defects (NTDs), and proactively prevent new cases of spina bifida and hydrocephalus, it is essential that women take folic acid well before becoming pregnant. Through the use of social networks, and the voice of healthcare professionals, it is hoped that more women than ever before will receive the Go Folic! message and start taking the 400mcg/day required to ensure the development of a healthy brain and spine.

4. Tomato
a. Lycopene
Lycopene, one of the powerful antioxidant in tomatoes, not only helps the immune system in neutralizing the forming of free radicals in the body and according to Harvard investigation as it found that men who ate more than 10 servings tomato-based foods daily (like cooked tomatoes and tomato sauce,) had a 35 percent lower risk of developing prostate cancer than those who ate the least amount of these foods. The benefits of lycopene was more pronounced with advanced stages of prostate cancer. Also according to the study of "Chemoprevention of prostate cancer with lycopene in the TRAMP model" by Konijeti R, Henning S, Moro A, Sheikh A, Elashoff D, Shapiro A, Ku M, Said JW, Heber D, Cohen P, Aronson WJ.(55)

b. Detoxification
Liver is a second defense that helps to clean out the toxins accumulation in the blood body. If the liver is over work, it can cause liver congestion, leading to lower of bile production or weaken carbohydrate metabolism. Since tomato contains high amount of Vitamins A and C, it not only supports liver function but stimulates the liver's function in detoxification of toxins., according to the study of "Effects of dried fish on antioxidant levels in rat liver" by Anilakumar KR, Khanum F, Krishna KR, Viswanathan KR. (56)

5. Lean meat (Beef)
a. Protein
In the research of the importance of dietary proteins influence body weight by affecting four targets for body weight regulation: satiety, thermogenesis, energy efficiency, and body composition, found that Ingestion of dietary proteins in diabetes type 1 exerts a delayed postprandial increase in blood glucose levels due to protein-induced stimulation of pancreatic glucagon secretion. Higher than minimal amounts of protein in the diet needed for nitrogen balance may play an important role for the increasing number of elderly obese subjects in our industrialized societies, since proteins exert beneficial effects in the conditions of overweight, metabolic syndrome, cardiovascular risk factors, bone health, and sarcopenia. Adverse effects of increased dietary proteins have been observed in subjects with renal impairment- this problem is frequently observed in the elderly, hypertensive, and diabetic population. Nevertheless, dietary proteins deserve more attention than they have received in the past, according to "Dietary proteins in obesity and in diabetes" by Keller U.(57)

b. Vitamin B complex
Beef contains high levels of vitamin B complex, including niacin, thiamin, riboflavin and B6, which aid each other for the body's metabolism, according to the article of "Vitamin B Complex", posted in the American cancer society, the author wrote that B vitamins are essential for growth, development, and a variety of other bodily functions. They play a major role in the activities of enzymes, proteins that regulate chemical reactions in the body(III), the formation of red blood cell formation and promoting the effectiveness of nervous system, according to the study of "The effect of 90 day administration of a high dose vitamin B-complex on work stress" by Stough C, Scholey A, Lloyd J, Spong J, Myers S, Downey LA., posted in PubMed (58).

c. Zinc
In the assessment of zinc and its effect on thyroid hormone and testosterone levels found that exercise decreases thyroid hormones and testosterone in sedentary men; however, zinc supplementation prevents this decrease. Administration of a physiologic dose of zinc can be beneficial to performance, according to "Effect of fatiguing bicycle exercise on thyroid hormone and testosterone levels in sedentary males supplemented with oral zinc" by Kilic M.(59)

6. Chicken
6. 1. Vitamin B complex

a) Vitamin B2 or Riboflavin is one of very important vitamin in metabolism of energy by helping the transforming of fats, proteins and carbohydrates and high dose riboflavin appears to be useful alone or along with beta-blockers in the prevention of migraine, according to the study of "Effectiveness of high-dose riboflavin in migraine prophylaxis. A randomized controlled trial" by Schoenen J, Jacquy J, Lenaerts M. (60)

b) Vitamin B3

Vitamin B3 or Niacin is essential for lowering high cholesterol levels, according to the study of "Cholesterol efflux potential and antiinflammatory properties of high-density lipoprotein after treatment with niacin or anacetrapib" by Yvan-Charvet L, Kling J, Pagler T, Li H, Hubbard B, Fisher T, Sparrow CP, Taggart AK, Tall AR., posted in PubMed (http://www.ncbi.nlm.nih.gov/pubmed/20448206), forming the components of cells' genetic material DNA during excision repair, according to the study of "Niacin deficiency delays DNA excision repair and increases spontaneous and nitrosourea-induced chromosomal instability in rat bone marrow" by

Kostecki LM, Thomas M, Linford G, Lizotte M, Toxopeus L, Bartleman AP, Kirkland JB., posted in PubMed (http://www.ncbi.nlm.nih.gov/pubmed/17618655) and treating diabetes and high blood sugar levels, according to the study of "Treatment of dyslipidemia in patients with type 2 diabetes" by Vijayaraghavan K., posted in PubMed (http://www.ncbi.nlm.nih.gov/pubmed/21172030), researcher indicated that a number of lipid-lowering agents, including statins, fibrates, niacin, and bile acid sequestrants, are available to target normalization of the entire lipid profile.

c) Vitamin B6

c. 1. Vitamin B6 or Pyridoxine beside is important in enhancing the developing red blood cells by stimulating the production of hemoglobin, it also helps to keep blood sugar levels steady during the process of breaking down stored energy in gestation pregnancy, according to the study of "Improvement of oral glucose tolerance in gestational diabetes by pyridoxine" by Bennink HJ, Schreurs WH., posted in PubMed (http://www.ncbi.nlm.nih.gov/pubmed/1131652)

c.2. It also plays a pivotal role as a methyl donor in the basic cellular process of methylation, through which methyl groups are transferred from one molecule to another, resulting in the formation of a wide variety of precess, including regulation of gene expression, protein function, and RNA metabolism. When levels of B6 are inadequate, it may cause faulty Methylation with high levels of homocysteine that can cause variety of disease, including cervical dysplasia, faulty detoxification and impaired DNA repair, etc., according to the study of "Back To Life Natural Health Center - Healthcare Through Natural Methods"(http://www.backtolifehealth.com/Methylation.htm)

d) Vitamin B12
In the evaluation of vitamin B12 in Turnip greens found that vitamin Bi2 was present in the
leaves of a higher plant in amounts. there is no evidence supporting the synthesis of vitamin Bi2 by a higher plant. Was it produced by soil microorganisms and subsequently absorbed via the plant roots? There is ample proof of such synthetic activity by certain microorganisms and of vitamin B12 activity in soil , but no evidence that the vitamin B]2molecule is absorbed by the plant from the soil. Could it have been produced by bacteria living epiphytically
on the turnip leaf? Ericson and Lewis ('54) postulated such a relationship in their studies of vitamin Bt2 compounds found in certain algae, according to "STUDIES OF VITAMIN B12IN TUENIP GREENS" by LOUISE F. GEAY ANDLOUISE J. DANIEL(http://jn.nutrition.org/content/67/4/623.full.pdf)

6.2. Protein
Protein beside is important building block of bones, muscles, cartilage, skin, and blood, it also enhances the nervous system in information transmitting between cells and cells of the other parts of the body, thus reducing the risk of nervous tension, (according to the study of "The planar polarity protein Scribble1 is essential for neuronal plasticity and brain function" by Moreau MM, Piguel N, Papouin T, Koehl M, Durand CM, Rubio ME, Loll F, Richard EM, Mazzocco C, Racca C, Oliet SH, Abrous DN, Montcouquiol M, Sans N, posted in PubMed (http://www.ncbi.nlm.nih.gov/pubmed/20660256)

6.3. Iron
Beside as a mineral in carrying life-giving oxygen to human blood cells and maintaining robust health as an essential protein component for metabolism, it also helps in synthesis of a number of essential neurotransmitters like dopamine, nor-epinephrine, along with serotonin. acccording to the study of "Brain Iron Dysregulation and the Risk of Ageing White Matter Lesions" by Gebril OH, Simpson JE, Kirby J, Brayne C, Ince PG., posted in PubMed, researchers found that The mRNA expression using QPCR suggests a pattern that favours decreased intracellular iron influx, increased ferrous oxidation and increased iron export from the cells. Iron metabolism seems to be changed in brains with WML, increased elemental iron in these brains and in turn increased production of free oxidative radicals could represent a potentiating factor for the development of ageing WML.

7. Flaxseed
a. Omega 3 fatty acids
Besides well known for its benefits for the maintenance of a healthy cardio-vascular system, according to the study of "Omega-3 Fatty acids for cardiovascular disease prevention" by Defilippis AP, Blaha MJ, Jacobson TA, posted in PubMed(I) and proper ratio of Omega 3 and 6 fatty acid and prevent blood clotting, it also extends the portion of your cycle in which you are fertile, by promoting natural ovulation, according tothe study of "Postpartum ovarian activity in multiparous Holstein cows treated with bovine somatotropin and fed n-3 fatty acids in early lactation" by Carriquiry M, Dahlen CR, Weber WJ, Lamb GC, Crooker BA., posted in pubMed (61)

b. Tryptophan
Tryptophan is one of the 10 essential amino acids which the body uses to synthesize the proteins for brain cells need, thus enhancing the nerve cells in information transmitting between themselves and cells in the parts of the body that reduces the risk of anxiety and depression, according to the study of "The effects of tryptophan depletion on neural responses to emotional words in remitted depression" by Roiser JP, Levy J, Fromm SJ, Nugent AC, Talagala SL, Hasler G, Henn FA, Sahakian BJ, Drevets WC.(62)

8. Salmon
a. Protein
In the research of the importance of dietary proteins influence body weight by affecting four targets for body weight regulation: satiety, thermogenesis, energy efficiency, and body composition, found that Ingestion of dietary proteins in diabetes type 1 exerts a delayed postprandial increase in blood glucose levels due to protein-induced stimulation of pancreatic glucagon secretion. Higher than minimal amounts of protein in the diet needed for nitrogen balance may play an important role for the increasing number of elderly obese subjects in our industrialized societies, since proteins exert beneficial effects in the conditions of overweight, metabolic syndrome, cardiovascular risk factors, bone health, and sarcopenia. Adverse effects of increased dietary proteins have been observed in subjects with renal impairment- this problem is frequently observed in the elderly, hypertensive, and diabetic population. Nevertheless, dietary proteins deserve more attention than they have received in the past, according to "Dietary proteins in obesity and in diabetes" by Keller U.(65)

b. Omega 3 fatty acids
Omega 3 fatty acids is necessary to maintain the ratio of good and bad cholesterol, thus reducing the risk of cholesterol inflammation according to the study of "In vitro fatty acid enrichment of macrophages alters inflammatory response and net cholesterol accumulation" by Wang S, Wu D, Lamon-Fava S, Matthan NR, Honda KL, Lichtenstein AH., posted in PubMed (66) and forming of free radical in the heart cells, leading to heart diseases. It also reduces the risk of plaque forming in the arterial wall, thus also decreasing the risk of stoke, according to the study of "N-3 vs. saturated fatty acids: effects on the arterial wall" by Sudheendran S, Chang CC, Deckelbaum RJ., posted in PubMed (67)

9. Etc.

VIII. ADHD in conventional medicine prospective
1. Diagnosis
Diagnosis depending to the observation of the symptoms of the children with ADHD and answering to questions about past and present problems, and a medical exam is also important to rule out other causes for symptoms. The diagnosis of children with development A is always a stressful and time consuming road for both parent and children, because each doctor in conventional medicine mostly specializes in one field and can not make any suggestion outside of his or her professional judgement. You may be recommended to see other specialists if one found to be necessary. Since ADHD is complex disease, it requires a team of doctor before it can be diagnosed correctly and many wrong diagnosis have been done, leading to overwhelming pressure and time wasting to the parent and their children. Fortunately, many cases of ADHD have been correctly diagnosed and are treated accordingly.
To avoid wasting your time, here is the basic list of doctors and specialists who have been required for all children with development disorder to be diagnosed correctly.
1. Development and behaviour pediatrician
2. Paediatric neurologist
3. Children psychiatrist
4. Children psychologist
5. Developmental/Behavioral Pediatricians
6. Occupational therapist
7. Neuropsychologists
8. Behavioral therapy
9. Social worker
Some children may require more or less specialists than the list above in their road to find a cure, but we believe the list is a basic team for fast and corrected diagnosis.

2. Treatments
Cognitive behavioral therapy and medication may be at least partially helpful in the treatment of children with ADHD or with ASD, if it is not accompanied with diet and nutrition as in Children with Autism, researchers said, according to the study "Effectiveness of nutritional interventions on the functioning of children with ADHD and/or ASD. An updated review of research evidence" by Martí LF., posted in PubMed(a)
2.1. Cognitive behavioral therapy
The aims of behaviour theory is to help the ADHD children to overcome the emotional, behavioural and cognitive dysfunction through a goal-oriented, systematic procedure. It is said that this types of treatment have proven to be successful in treating mood, anxiety, personality, eating, substance abuse, and psychotic disorders in some degrees.

2.2. Exercise
Research is demonstrating that acute exercise facilitated performance in the Stroop Test, particularly in the Stroop Color-Word condition. Additionally, children in the exercise group demonstrated improvement in specific WCST performances in Non-perseverative Errors and Categories Completed (10)

2.3. Parental Training
Parental Training in early alliance and change in alliance over time predicted improvements in several parenting behaviors and child outcomes, including peer sociometrics in a lab-based playgroup. These preliminary findings lend support to the importance of examining the parent-therapist alliance in parent-training groups for youth social and behavioral problems (11). Even though it is always difficult for parent to try them in the beginning, but be consistent. follow through on punishments and rewards. Keep rewards frequent and short-term, etc.

2.4. Occupational therapy
Occupational therapy is a type of program, helping to compromise physically, intellectually or emotionally to integrate coping skills into their lives in order to perform necessary tasks. but for children with ADHD, the main goal of occupational therapy is to integrate sensory perception through recognition and interpretation of sensory stimuli based chiefly on memory, therefore it helps the child to gain a more peaceful frame of mind and concentrate on certain tasks.

2.5. Social skill training
Social skill training plays an important role for many children with ADHD to learn social skills for improving relationships with peers for the child and formed part of the ADHD treatment.

2.6. Make Environment ADHD Friendly
Some researchers suggested that making environment friendly may be essential for children with ADHD such as reduce distractions and strategies for keeping attention for the ADHD children

2.7. Medication
Stimulants are used to treat and manage ADHD. All stimulants involved the increasing levels of dopamine, a neurotransmitter in the brain associated with pleasure, movement, and attention.
a. Methylphenidate , including Biphentin®, Concerta® or Ritalin®)
a. 1. Methylphenidate is a piperidine compounds used to treat ADHD by increasing the levels of dopamine and norepinephrine in the brain byreleasing medication in the body over a period of time to prvide a paradoxically calming and attention effect on individuals with ADHD. Some researchers have found the beneficial effects of methylphenidate for both boys and girls. Methylphenidate therefore would appear to be as useful a treatment for ADD girls as for ADD boys.(22)
a.2. Side Effects are not limit to
a.2.1. It can be addictive
a.2.2. the medication of can cause nervousness including dizziness, agitation, anxiety and irritability
a.2.3. It may also cause gastrointestinal disorders including stomach ache, nausea, decreased appetite, vomiting, etc.
a.2.4. Do not use the medication if you have high blood pressure or any form of heart disease
a.2.5. The medicine is easy to abuse and toxicity
As therapeutic use increases, the risk increases of unintentional overdoses, medication errors, and intentional overdoses caused by abuse, misuse, or suicide gestures and attempts. Side effects during therapy, which include nervousness, headache, insomnia, anorexia, and tachycardia, increase linearly with dose. Clinical manifestations of overdoses include agitation, hallucinations, psychosis, lethargy, seizures, tachycardia, dysrhythmias, hypertension, and hyperthermia(23)
a.2.6. Etc.

b. Dextroamphetamine (Dexedrine®, amphetamine mixed salts (Adderall XR®)
b.1. Dextroamphetamine used as part of a treatment program to control symptoms of attention deficit hyperactivity disorder (ADHD, is a central nervous system stimulants used by changing the amounts of certain natural substances in the brain in which involved the effect in wakefulness and focus as well as decreased fatigue and decreased appetite.
b.2. Side Effects are not limit to
b.2.1. Prolonged period of use may decrease the effectiveness of the medicine
b.2.2. Over doses or using can cause cause serious heart problems or sudden death.
b.2.3. The medicine can cause nervous tension, including restlessness, difficulty falling asleep or staying asleep, headache, uncontrollable shaking of a part of your body , etc.
b.2.4. Dextroamphetamine can also cause digestive
disorder, including diarrhea, constipation loss of appetite, etc.
b.2.5. abuse, misuse, and diversion
Although, evidence on abuse, misuse, and diversion was limited, if compare to the use of Methylphenidate. But misuse and diversion rates varied by age and were highest among college students, and rates of diversion were highest with amphetamine-based products but similar among methylphenidate products. Evidence of effects in important subgroups of patients with ADHD (e.g. comorbid anxiety) was not comparative.(24)

c. Lisdexamfetamine (Vyvanse®)
c.1. Lisdexamfetamine dimesylate (LDX) is the medicine used in children with and without previous exposure to stimulant medication in the treatment of attention-deficit/hyperactivity disorder (ADHD) as a significantly less active form to dextroamphetamine. As LDX reduced the core symptoms of ADHD with more severe adverse events in stimulant-naïve than previous-exposure subjects. Future controlled studies with larger samples should address the impact of previous stimulant exposure on other ADHD treatments(25)
c.2. Side effects are not limit to
c.2.1. The medication can cause nervous tension, including mild irritability, nervousness, restlessness, dizziness, trouble sleeping, etc.
c.2.2. Lisdexamfetamine dimesylate can also cause digestive disorders, including, constipation, decreased appetite, diarrhea, dry mouth, nausea, stomach pain; vomiting, etc.
c.2.3. It may be subject to abuse cause as increased risk for impairment in driving behaviors.(26)
c.2.4. Etc.

2.8. Etc.

IX. In Nutritional Supplement perspective
1. Caffeine (Adult only, please)
Some researchers suggested that caffeine administration cause a significant improvement in the attention deficit of the 6-OHDA in lesioned rats(30) and demonstrate a selective spatial learning deficit in SHR which can be attenuated by pre-training administration of caffeine. In addition, the present findings indicate that the spatial learning deficit in SHR is not directly related to hypertension(31)

2. Omega 3 fatty acid
High intake of Omega 3 fatty acid has been associated with a reduced risk of Alzheimer's disease (AD) and enhanced neuroprotective effect, including mild form of cognitive impairment(39)
researchers found that lower levels of long-chain polyunsaturated fatty acids, particularly omega-3 fatty acids, in blood have repeatedly been associated with a variety of behavioral disorders including attention-deficit/hyperactivity disorder (ADHD)(38).

3. Antioxidants
Antioxidants have been proven to be effective in fighting against the forming of free radicals of which can damage to the DNA of the cells, particular to brain cells. Some researchers suggested that oxidative stress may be a factor underlying the pathophysiology of bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SCZ) as a result of of reduced levels of Glutathione (GSH), a major free radical scavenger in the brain(41)

4. Vitamin B complex
It is also known as B vitamins (vitamins B1, B2, B3, B5, B6, B7, B9, and B12). B vitamins beside play a major role in regulating chemical reactions in the body, it also have been linked to improve neurodegenerative and cerebrovascular disease. Study showed that B-vitamin deficiency and/or hyperhomocysteinemia can cause a variety of neurological and vascular deficits in animals.(45)

5. Protein
Proteins beside serve as a fuel source, they also are essential nutrients for the human body and as one of the building blocks of the body, protein deficiency can lead to variety of ailments including mental retardation, including learning disability.

6. Calcium and magnesium
Calcium beside is best known for helping build strong bones, it also enhances the durable process cell membranes and promotes the nervous system, especially in neurotransmitter release, triggered by the arrival of a nerve impulse of which could improve a child's behavior.

Magnesium beside maintains normal muscle and nerve function, keeps heart rhythm steady, it also promotes a healthy immune system, and maintains bones strong. some reserachers suggestedthat symptoms of hyperexcitability (physical aggressivity, instability, scholar attention, hypertony, spasm, myoclony) were reduced after 1 to 6 months treatment. Other family members shared similar symptoms, had low ERC-Mg values, and also responded clinically to increased Mg(2+)/vitamin B6 intakes.(44)

7. Trace minerals
Trace minerals are micronutrients that have played a vital role in the body's function but with a small amount. Zinc is an essential mineral that is naturally present in some foods and as an essential cofactor of more than 100 enzymes, including metalloenzymes and metalloenzyme complexes, which are necessary in the metabolism of carbohydrates, fatty acids, proteins and nucleic acids. In recent studies estimate its prevalence to three of ten hyperactive children, and there are data that about 4% of children have the complete frame of the disorder, researchers suggested that children with ADHD have low levels of zinc in their bodies compared to children without ADHD may be a result of zinc deficiency (42). In a controlled comparison group study, (Konofal et al. 2004) showed that iron deficiency was correlated to ADHD symptoms severity, hypothesizing that iron supplementation may improve symptoms of ADHD in those subjects with low ferritin levelsmitter dopamine of which may help children with ADHD.(43)

X. In Herbal medicine perspective
Herbal medicine believe ADHD is a result of coordination failure in the reticular activating system of the brain. Therefore, herbs used to treat ADHD are those improves concentration, attention, motivation and performance, promote the stay on task and normal energy levels and particular enhance the flow of oxygen and nutrients to the brain and supports brain functions in information processing and memory, etc.
1. Ginkgo Biloba
a. Brain-cognition effects
Ginkgo Biloba extract (GBE) have exhibited the function of alleviating symptoms of cognitive impairment in aging populationby increasing the SSVEP(state visually evoked potentia) amplitude at occipital and frontal sites and SSVEP latency at left temporal and left frontal sites, according to the study of "Examining brain-cognition effects of ginkgo biloba extract: brain activation in the left temporal and left prefrontal cortex in an object working memory task" by Silberstein RB, Pipingas A, Song J, Camfield DA, Nathan PJ, Stough C., posted in PubMed(67)

b. Acute cognitive effects
Administration of GBE complexed with phosphatidylserine have exerted the results of improingsecondary memory performance and speed of memory task performance, according to the study of "Acute cognitive effects of standardised Ginkgo biloba extract complexed with phosphatidylserine" by Kennedy DO, Haskell CF, Mauri PL, Scholey AB., posted in PubMed(68)

c. Tardive dyskinesia
Extract of Ginkgo biloba (EGb) has exerted the activity as an antioxidant in scavenging free radicals for tardive dyskinesia (TD) in in schizophrenia patients by significantly decreased the AIMS(Abnormal Involuntary Movement Scale) total score in patients with TD, according to the study of "Extract of Ginkgo biloba treatment for tardive dyskinesia in schizophrenia: a randomized, double-blind, placebo-controlled trial" by Zhang WF, Tan YL, Zhang XY, Chan RC, Wu HR, Zhou DF., posted in PubMed(69)

d. Etc.

2. Panax ginseng
a. Antioxidant activity
In the evaluation of the extraction conditions of polysaccharides from the rhizomes of Panax japonicus C.A. Meyer and its antioxidant effect found that antioxidant activity exhibited Panax japonicus polysaccharides (PJP) had a good potential for antioxidant, according to "Optimization of polysaccharides from Panax japonicus C.A. Meyer by RSM and its anti-oxidant activity" by Wang R, Chen P, Jia F, Tang J, Ma F.(70)

b. Antipsychotic effect
In the investigation of Panax quinquefolium (PQ) and its significant neuroactive properties for its antipsychotic potential found that PQ blocked ketamine induced memory impairment in the passive avoidance paradigm. In the chronic studies, PQ reduced the ketamine induced enhanced immobility in the forced swim test and did not show extra-pyramidal side effects in bar test and wood block test of catalepsy. These behavioural effects were compared with standard drugs haloperidol and clozapine. Further PQ reduced DA and 5-HT content after chronic treatment, but not after acute administration, according to "Evaluation of the Antipsychotic Potential of Panax quinquefolium in Ketamine Induced Experimental Psychosis Model in Mice" by Chatterjee M, Singh S, Kumari R, Verma AK, Palit G.(71)

c. Neuroprotective effect
In the analyzing Panax ginseng C.A. Meyer and its beneficial effects in cerebral ischemia and inhibition of the inflammatory cascade in sepsis found that Ginsenoside Rb1 (GRb1) partially inhibited the activation of nuclear factor-κB (NF-κB) pathway from 6 h to 72 h after ischemia and reperfusion onset, as determined by the expression of total and phosphorylated NF-κB/p65, inhibitor protein of κB (IκB)-α, and IκB-kinase complex (IKK)-α. All these results indicate that suppression of local inflammation after cerebral ischemia might be one mechanism that contributes to the neuroprotection of GRb1, according to "Suppression of local inflammation contributes to the neuroprotective effect of ginsenoside Rb1 in rats with cerebral ischemia" by Zhu J, Jiang Y, Wu L, Lu T, Xu G, Liu X.(72)

d. Immunological activities
In the study of Water-soluble ginseng oligosaccharides (designated as WGOS) with a degree of polymerization ranging from 2 to 10 were obtained from warm-water extract of Panax ginseng roots, found that WGOS were potent B and T-cell stimulators and WGOS-1 has the highest immunostimulating effect on lymphocyte proliferation among those purified fractions. It is hoped that the WGOS will be developed into functional food or medicine, according to "Structural characterization and immunological activities of the water-soluble oligosaccharides isolated from the Panax ginseng roots" by Wan D, Jiao L, Yang H, Liu S.(73)

e. Etc.

3. Skullcap
a. Liver diseases
In the evaluation of the anti-proliferative effects on human hepatoma HepG2 and Hep3B cells of each fraction of Pheophorbide a, a major antitumor component purified from Scutellaria barbata, found that pheophorbide a induced apoptosis in Hep3B cells, a viral-induced hepatoma cell line. However, it was found to be non-toxic in normal human liver cells WRL-68. DNA fragmentation, sub-G1 cell cycle arrest, as well as suppression of the anti-apoptotic protein Bcl-2, release of cytochrome c to the cytosol, and activation of pro-caspase 3 and pro-caspase 9 were observed when Hep3B cells were treated with 40 microg/mL (i. e., 67.5 microM) pheophorbide a for 48 hours, according to "Pheophorbide a, a major antitumor component purified from Scutellaria barbata, induces apoptosis in human hepatocellular carcinoma cells" by Chan JY, Tang PM, Hon PM, Au SW, Tsui SK, Waye MM, Kong SK, Mak TC, Fung KP.(74)

b. Antioxidants
In the Comparisons of Scutellaria baicalensis, Scutellaria lateriflora and Scutellaria racemosa: genome size, antioxidant potential, found that Antioxidant potential studies showed that there were no significant differences in the 3 Scutellaria species. Phytochemical analyses detected and quantified the flavonoids baicalin, baicalein, scutellarin, and wogonin as well as the human neurohormones melatonin and serotonin in leaf and stem tissues from S. baicalensis, S. lateriflora, and S. racemosa, according to "Comparisons of Scutellaria baicalensis, Scutellaria lateriflora and Scutellaria racemosa: genome size, antioxidant potential and phytochemistry" by Cole IB, Cao J, Alan AR, Saxena PK, Murch SJ.(75)

c. Neurodegeneration diseases
In the study of flavones isolated from Scutellaria baicalensis root exhibit strong neuroprotective effects on the brain, found that Baicalein, the main flavone present in Scutellaria baicalensis root, strongly inhibited aggregation of neuronal amyloidogenic proteins in vitro and induces dissolution of amyloid deposits. It exerts strong antioxidative and anti-inflammatory activities and also exhibits anti-convulsive, anxiolytic, and mild sedative actions. Importantly, baicalein, and also another flavone: oroxylin A, markedly enhanced cognitive and mnestic functions in animal models of aging brains and neurodegeneration, according to "Flavones from root of Scutellaria baicalensis Georgi: drugs of the future in neurodegeneration?" by Gasiorowski K, Lamer-Zarawska E, Leszek J, Parvathaneni K, Yendluri BB, Błach-Olszewska Z, Aliev G.(76)

d. Anxiolytic activity
In the investigation of the phytochemistry and biological activity of Scutellaria lateriflora L. (American skullcap) which has been traditionally used as a sedative and to treat various nervous disorders, found that these compounds may play a role in anxiolytic activity since baicalin and baicalein are known to bind to the benzodiazepine site of the GABAA receptor and since GABA is the main inhibitory neurotransmitter, according to "Phytochemical and biological analysis of skullcap (Scutellaria lateriflora L.): a medicinal plant with anxiolytic properties" by Awad R, Arnason JT, Trudeau V, Bergeron C, Budzinski JW, Foster BC, Merali Z.(77)

e. Etc.

4. Gotu Kola
a. Locomotor activity
In the investigation of the asiatic acid, a triterpenoids isolated from Centella asiatica and its inhibitory effect on acetylcholinesterase (AChE) properties, excitatory post synaptic potential (EPSP) and locomotor activity. found that asiatic acid having an effect on AChE, a selective GABA(B) receptor agonist and no sedative effect on locomotor, according to "Inhibitory effect of asiatic acid on acetylcholinesterase, excitatory post synapticpotential and locomotor activity" by Nasir MN, Abdullah J, Habsah M, Ghani RI, Rammes G.(78)

b. Cognitive effects
In the assessment of the role of "Brahmi" (Bocopa monnieri and Centella asiatica) and its effect on the loss of memory, cognitive deficits, impaired mental function found that both plants possess neuroprotective properties, have nootropic activity with therapeutic implications for patients with memory loss. The field has witnessed exciting patent activity with most inventions aiming at either (i) improving the methods of herbal extraction or (ii) enrichment and purification of novel compounds from brahmi or (iii) providing novel synergistic formulations for therapeutics in various human ailments, according to "Exploring the role of "Brahmi" (Bocopa monnieri and Centella asiatica) in brain function and therapy" by Shinomol GK, Muralidhara, Bharath MM.(79)

c. Antioxidant capacity
In the identification of antioxidant effects of C. asiatica was exposed to various fermentations: no fermentation (0 min), partial fermentation (120 min) and full fermentation (24 h). Total phenolic content (TPC) and ferric-reducing antioxidant power (FRAP) of C. asiatica, found that C. asiatica herbal teas should be prepared at 100 °C for 10 min to obtain the optimum antioxidant capacity. Multiple brewing steps in C. asiatica herbal tea are encouraged due to the certain amount of antioxidant obtained, according to "Antioxidant capacity and phenolic composition of fermented Centella asiatica herbal teas" by Ariffin F, Heong Chew S, Bhupinder K, Karim AA, Huda N.(80)

d. Etc.

5. Chamomile
a. Anti-allergic activity
The methanol extract of Matricaria recutita L. has shown anti-allergic activity by inhibition of histamine release from mast cells, according to the study of "Anti-allergic activity of German chamomile (Matricaria recutita L.) in mast cell mediated allergy model" by Chandrashekhar VM, Halagali KS, Nidavani RB, Shalavadi MH, Biradar BS, Biswas D, Muchchandi IS.(81)

b. Neuroprotective activity
German chamomile methanol extract (GCME) has shown shown the ability to treat neuroprotective activity by significant decrease in lipid peroxidation (LPO) and increase in the superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and total thiol levels, against AlF₄⁻- and may be used to treat oxidative brain damage, according to the study of "Neuroprotective activity of Matricaria recutita against fluoride-induced stress in rats" by Ranpariya VL, Parmar SK, Sheth NR, Chandrashekhar VM.(82)

c. Anxiety
Matricaria recutita (chamomile) extract therapy has exerted the modest anxiolytic activity in patients with mild to moderate generalized anxiety disorder, according to the study of "A randomized, double-blind, placebo-controlled trial of oral Matricaria recutita (chamomile) extract therapy for generalized anxiety disorder" by Amsterdam JD, Li Y, Soeller I, Rockwell K, Mao JJ, Shults J.(83)

d. Etc.

6. Hawthorn
a. Neuroprotective effects
In the investigation of the neuroprotective effects on PC12 cells from the methanol extracts of Spatholobus suberectus, Uncaria rhynchophylla, Alpinia officinarum, Drynaria fortunei, and Crataegus pinnatifida found that The CPE, SSE, and URE presented neurogrowth effects and neuroprotective activities on H(2)O(2)-induced PC12 cell death at 0.5-5.0 μg/mL. The CPE represents a promising medicinal plant source for the treatment of H(2)O(2)-induced neurodegenerative disease, because of its useful phytochemical characteristic, according to "Phytochemical characteristics, free radical scavenging activities, and neuroprotection of five medicinal plant extracts" by Chang CL, Lin CS, Lai GH.(84)

b. Immunomodulatory effect
In the determination of sheds more light on the extract's mechanism of neuroprotection, especially its immunomodulatory effect found that Hawthorn extract helped alleviate pro-inflammatory immune responses associated with I/R-induced injury, boosted IL-10 levels, and increased Foxp3-positive T(regs) in the brain, which may have aided in suppression of activated inflammatory cells. Such treatment also minimizes apoptotic cell death by influencing STAT-3 phosphorylation and Bcl-xL expression in the brain. Taken together, the immunomodulatory effect of Hawthorn extract may play a critical role in the neuroprotection observed in this MCAO-induced stroke model, according to "Immunomodulatory effect of Hawthorn extract in an experimental stroke model" by Elango C, Devaraj SN.(85)

c. Prevention and treatment of cataracts
In the evaluation of the anticataract potential of Crataegus pinnatifida (hawthorn tree) leaves and its extract in selenite-induced cataract in vivo and antioxidant effects in vitro, found that administration of C. pinnatifida leaves extract eye drops alternately three times a day in rat pups with selenite-induced oxidative stress significantly increased serum SOD and CAT activities, and tended to reduce MDA level compared with control group. The antioxidant enzyme SOD, CAT, and GSH activities in lens showed a significant increase. These results may be applied in the future for the prevention and treatment of cataracts, according to "Prevention effect in selenite-induced cataract in vivo and antioxidative effects in vitro of Crataegus pinnatifida leaves" by Wang T, Zhang P, Zhao C, Zhang Y, Liu H, Hu L, Gao X, Zhang D.(86)

7. Green oat (Avena sativa)
a. Magnesium
Magnesium not only important for bone health, according to the study of "Magnesium, zinc, copper, manganese, and selenium levels in postmenopausal women with osteoporosis. Can magnesium play a key role in osteoporosis?" by Odabasi E, Turan M, Aydin A, Akay C, Kutlu M(87) but also play and important role in protecting against Alzheimer's disease, according to the study of "Altered ionized magnesium levels in mild-to-moderate Alzheimer's disease" by Barbagallo M, Belvedere M, Di Bella G, Dominguez LJ.(88)

b. Avenanthramides
The ingredients of avenanthramides and phenolic acids in oat protect the LDL cholesterol against the forming of free radicals by inducing the functions of copper and selenium against oxidation, according to the study of "Avenanthramides and phenolic acids from oats are bioavailable and act synergistically with vitamin C to enhance hamster and human LDL resistance to oxidation" by Chen CY, Milbury PE, Kwak HK, Collins FW, Samuel P, Blumberg JB., posted in PubMed(89)

c. Immune system
Selenium in Oat improves the immune system in fighting the foreign invasion of virus and bacteria causes of infection and inflammation, according to the study of "Selenium in the immune system" by Arthur JR, McKenzie RC, Beckett GJ., posted in PubMed(90)

8. Etc.

XI. In traditional Chinese medicine perspective(66)
Although there are no condition known as ADD, in the history of Chinese medicine, but some TCM practictioners defined ADHD as result as follow
A. Predominantly hyperactive-impulsive as of result of Kidney Yin deficiency cause of hyperactivities of liver Yang
1. Symptoms
Beside the symptoms mentioned above, TCM also describes the physical appearance of the patient as follow
a. Thin body
b. Thristy
c. Desire to cold
d. night sweat
e. Red tongue with less coating
f. Etc.

2. Treatment
Qi Ju Di Huang Wan, the TCM formula with main function in nourishing the kidney and liver, improves vision used for patient with above symptoms and for deficiency of both liver Yin and kidney-Yin. Ingredients include
a. Shu Di Huang
The bitter, sweet, bitter and warm herb has been used in as diuretic agent and to enhance heart function (small doses constrict the blood vessels and large doses dilate the blood vessel), decrease blood sugar, etc., as it clears Heat and cools the Blood (Sheng) as it nourishes Yin and Blood, tonifies the Essence, strengthens the Marrow, etc., by enhancing the functions of heart, kidney, and liver channels.

b. Shan Zhu Yu
Shan Zhu Yu or Shan Yu Rou is also known as Asian Cornelian Cherry Fruit. The sour, acrid and slightly warm herb has been used in TCM to treat impotence, spermatorrhea, instant sweating, sore or week knees, chronic lower back pain, frequent urination, incontinence, etc., as it tonifies the Liver and the Kidneys, benefits the Liver and the Kidneys, etc., by enhancing the functions of kidney and liver channels.

c. Shan Yao
Shan Yao or Huai Shan is also known as Dioscorea. The sweet and neutral herb has been used in TCM as antibiotic , anti-inflammatory and anti aging agent and to lower blood sugar, improve digestive system, promote urination, etc. as it tonifies the spleen and stomach and kidney yang and yin, etc., by enhancing the functions of kidney, lung and spleen channels.

d. Ze Xie
Ze Xie is also known as Alism. The sweet, bland and cold herb has been used in TCM as anti-pyretic, diuretic, anti-bacterial, hypoglycemic, hypotensive agent and to lowers blood lipids: total cholesterol, inhibits hardening of main artery, etc., as it drains deficient kidney fire, promotes urination, drains damp-heat, etc., by enhancing the functions of kidney and bladder channels.

e. Fu Ling
Fu Ling, fu shen or fu ling pi is also known as Poria. The bland, sweet and neutral herb has been used in TCM as as diuretics and to treat urinary difficulty, diarrhea, water retention, headache, dizziness, palpitations, etc., as it eliminates Water, strengthens the Spleen, calms the Mind, etc., by enhancing the functions of heart, spleen, lung and kidney channels.

f. Mu Dan Pi
Mu Dan Pi or Dan Pi is also known as peony bark. The acrid, bitter and mildly cool has been used in TCM as anti micro organism, anti inflammatory agent and to enhance circulation, CNS as it clears heat, fire of yin deficiency, blood stasis and cools the blood, etc., by enhancing the functions of heart, liver and kidney channels.

g. Gou Qi Zi
The sweet and neutral herb has been used in TCM as anti aging and anti cancer agent and to enhance the immune system, lower blood lipids, elevate level of testosterone, protect the liver function, prevent fatty liver, simulate estrogens, etc., as it nourishes and tonifies the liver, lung and kidney, etc., by enhancing the functions of liver, lung and kidney channels.

h. Ju Hua
Ju Hua is also known as chrysanthemum flower. The nsweet, bitter and slightly cold herb has been used in TCM as anti inflammatory, antibiotic, anti Antipyretic agent and to treat liver and kidney deficiency resulting in dizziness, blurry vision, pain and weakness in lower back and knees, tears induced by wind blowing, as it disperses wind, clears heat and wind-heat, et., by enhancing the functions of liver and lung channels.

B. Predominantly inattentive as of result of Qi and blood deficiency of Spleen and Heart causes of failing to nourish the heart Mind
1. Symptoms
Beside the symptoms mentioned above, TCM also describes the physical appearance of the patient as follow
a. Pale face and lips
b. Overactive with low energy
c.Poor memory
d. Pale tongue and weak pulse
f. Etc.

2. Treatment
Gui Pi Tang helps to strengthens the spleen and the heart, nourishes blood and Qi, calms the mind. Ingredients include
a. Fu Ling
Fu Ling, fu shen or fu ling pi is also known as Poria. The bland, sweet and neutral herb has been used in TCM as as diuretics and to treat urinary difficulty, diarrhea, water retention, headache, dizziness, palpitations, etc., as it eliminates Water, strengthens the Spleen, calms the Mind, etc., by enhancing the functions of heart, spleen, lung and kidney channels.

b. Bai Zhu
Bai Zhu is also known as Bighead atractylodes rhizome. The aromatic, slightly acrid and sweet herb has been used in TCM to treat children drooling, Meniere's disease, constipation, chronic back painm, acute infection of intestine, dizziness, palpitation, edema, instant sweating, etc., as it tonifies the spleen, augments qi, dries dampness, atabilizes the exterior, etc., by enhancing the functions of spleen and stomach channels.

c. Suan Zao Ren
Suan Zao Ren is also known as Sour jujube seed. The sweet, sour, neutral herb has been used in TCM to treat abnormal sweating, anxiety, insomnia, excessive dream, palpitation, weak memory, dizziness, night sweating, etc., as it nourishes heart and liver, calms spirit, etc., by enhancinf the functions of gallbladder, heart, liver and spleen channels.

d. Huang Qi
Huang Qi or Bei Qi is also known as Astragalus root. The sweet herb has been used as diuretic agent and to lower blood pressure, increase blood pressure, lessens proteinuria, improve endurance, protect liver function, regulate blood sugar, etc. as it tonifies Qi, raises Yang, strengthens the Defensive-Qi and the Exterior, expels toxins, etc. by enhancing the functions of lung and spleen channels.

e. Dang Shen
Dang Shen is also known as codonopsis root. The sweet and neutral herb has been used in TCM to enhance the immune and cetral nervous systems and blood coagulation, reduce fatigue, increases red and white blood cells, white blood cells, raise blood sugar, etc., as it tonifies the Middle, strengthens Qi, promotes generation of Body Fluids, nourishes Blood, etc., by promoting the functions of lung and spleen channels.

f. Long Yan
Long Yan or Long Yan Rou is also known as Longan. The aromatic and neutral herb has been used in TCM to treat neurasthenia, forgetfulness, palpitation, insomnia, etc., as it tonifies heart and spleen, nourishes blood, calms spirit, etc., by enhancing the functions of heart and spleen channels.

g. Da Jiao
Da Jiao or Da Zao also known as black jujube. The sweet and warm herb has been used in TCM to treat improves cAMP(cyclic adenosine mono phosphate) and strength of muscles, calms the central nervous system, inhibits histamine, IgE, and 5-HT, cell mutation and cancer cells, etc., as it tonifies the Middle Burnner, strengthens Qi, nourishes Blood, calms the Mind, regulates the nature of other herbs, etc., by enhancing the functions of stomach , spleen channels.

h. Dang Gui
Dang Qui is also known as Angelica Root. The sweet, bitter, acrid and warm herb has been used in TCM to regulate the menses, lower lipids, reduce platelet coagulation and swelling, expel pus, relieve pain, etc/, as it tonifies and moves Blood, calms pain, moistens the Intestines, etc., by enhancing the function of heart, liver and spleen channels.

i. Yuan Zhi
Yuan Zhi is also known as Turkey Tails. The sweet, bland and slightly cold herb has been used in TCM as antibiotic property, anti-viral property, and anti-tumor agent and to get rid of dampness, transform phlegm, treat lung disease, insomnia, mental confusion, seizures, palpitations, anxiety, restlessness, etc., as it calms the spirit, quiets the heart, expels phlegm, clears the heart orifices, etc., by enhancing the functions of liver, spleen and lung channels.

j. Gan Cao
Gan Cao is also known as Licorice root. The sweet and neutral herb has been used in TCM as anti allergy, anti inflammation, anti ulcer, anti convulsion and to treat stomach weakness, tired and lack of strength, palpitation and short of breath, cough with abundance of phlegm, stomach and solar plexus pain, etc., as it tonifies the Spleen, benefits the Qi, moistens the Lungs, calms cough, deaf or acute pain, by enhancing all 12 channels.

k. Sheng Jiang
Sheng Jiang is also known as Fresh Ginger root. The acrid and cool herb has been use in TCM as an anti inflammation, anti coagulation of platelets, anti allergy, anti tumors, etc, and to promote flowing of bile, protect liver, stimulate cardiac function, inhibit platelet coagulation, prevent dizziness, improve auto-immune function,etc., as it promotes sweating, releases the Exterior; warms the Middle Burner and the Lungs, stops vomiting, calms cough by enhancing the functions of lung, spleen and stomach channels.

l. Mu Xiang
Nu Xiang is also known as costus root. The acrid, bitter and warm hrtb has been used in TCM to treat flatulence and pain in the abdomen, diarrhea, bronchitis, digestive tract infection: yeast infection, dysentery, and lack of appetite, etc,, as it promotes the movement of Qi, alleviates pain, regulates stagnated Qi in the intestines, strengthens the spleen and prevents stagnation, etc., by enhancing the functions of gallbladder, large intestine, spleen and stomach channels.

C. Anxiety, vexed, easily forgetful as of result of deficiency of Kidney essence causes of failing to nourish heart and Brain
1. Symptoms
a. Insomnia
b. Easily forgetful
c. Sores tongue
d. Red tongue
e. Rapid pusle
f. Etc.

2. Treatment
Kong Sheng Zhen Zhong Dan
A formula from Confucius to treat students with above symptoms and enhance education achievement by tonifying kidney, heart and benefiting the brain.
a. Shi Chang Pu
Shi Chang Pu is also known as Sweetflag Rhizome. The pungent, aromatic and warm herb has been used in TCM to treat deafness, dizziness, poor memory, dulled sensation, seizures, etc., as it opens orifices,expel phlegm, quiets spirit, -harmonize middle burner, etc., by enhancing the functions of heart ans stomach channels.

b. Yuan Zhi
Yuan Zhi is also known as Turkey Tails. The sweet, bland and slightly cold herb has been used in TCM as antibiotic property, anti-viral property, and anti-tumor agent and to get rid of dampness, transform phlegm, treat lung disease, insomnia, mental confusion, seizures, palpitations, anxiety, restlessness, etc., as it calms the spirit, quiets the heart, expels phlegm, clears the heart orifices, etc., by enhancing the functions of liver, spleen and lung channels.

c. Long gu
Long gu is also known as keel. The sweet, sour and neutral herb has been used in TCM to treat mood, palpitation, excessive dreams, irritability, seizures, dizziness, insomnia, forgetfulness, etc. as it calms spirit/heart and calms liver, anchors floating Yang, etc., by enhancing the functions of heart, liver, large intestine and kidney channels.

d. Baked Gui Ban
Gui Ban, Giu Jia or Gui Ban Jiao Is also known as Fresh Water Turtle Shell. The salty, sweet and neutral herb has been used in TCM to treat hot flashes with night sweating, chronic ache in loin and knees, spermatorrhea, chronic cough, palpitation, insomnia and forgetfulness, excesive bleeding during menses, etc., as it nourishes Yin, subdues Yang, tonifies the Kidneys and Heart, strengthens the Bones, Nourishes Blood, etc., by enhancing the functions of liver, kidney and heart channels.

Author notes: All articles written by Kyle J. Norton are for information and education only, please consult with your doctor or related field specialist before applying.

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