Focal

Panax Quinquefolii (Xi Yang Shen)

Effect of the herbal extract combination Panax quinquefolium and Ginkgo biloba on attention-deficit hyperactivity disorder: a pilot study.

Lyon MR, Cline JC, Totosy de Zepetnek J, Shan JJ, Pang P, Benishin C. Psychiatry Neurosci. 2001 May;26(3):221-8.

Objective: A combination herbal product containing American ginseng extract, Panax quinquefolium, and Ginkgo biloba extract was tested for its ability to improve the symptoms of attention-deficit hyperactivity disorder (ADHD). Design: Open study. Patients: 36 children ranging in age from 3 to 17 years who fit the diagnostic criteria for ADHD. Interventions: capsules were taken twice a day on an empty stomach for 4 weeks. After 2 weeks of treatment, the proportion of the subjects exhibiting improvement (i.e., decrease in T-score of at least 5 points) ranged from 31% for the anxious-shy attribute to 67% for the psychosomatic attribute. After 4 weeks of treatment, the proportion of subjects exhibiting improvement ranged from 44% for the social problems attribute to 74% for the Conners' ADHD index and the DSM-IV hyperactive-impulsive attribute. Five (14%) of 36 subjects reported adverse events, only 2 of which were considered related to the study medication. Conclusions: These preliminary results suggest this treatment may improve symptoms of ADHD and should encourage further research on the use of ginseng and Ginkgo biloba extracts to treat ADHD symptoms.

Zinc

Zinc has a range of functions. It plays a crucial role in growth and cell division where it is required for protein and DNA synthesis, in insulin activity, in the metabolism of the ovaries and testes, and in liver function. As a component of many enzymes, zinc is involved in the metabolism of proteins, carbohydrates, lipids and energy.

Our body contains about 2-3g of zinc. There are no specific storage sites known for zinc and so a regular supply in the diet is required. Zinc is found in all parts of our body, 60% is found in muscle, 30% in bone and about 5% in our skin. Particularly high concentrations are in the prostate gland and semen. Men need more zinc than women because male semen contains 100 times more zinc than is found in the blood. The more sexually active a man the more zinc he will require. The recommended amounts of zinc for adult men are 1/3 higher than those for women.

Iron

Iron has the longest and best described history among all the micronutrients. It is a key element in the metabolism of almost all living organisms. In humans, iron is an essential component of hundreds of proteins and enzymes.

Heme is an iron-containing compound found in a number of biologically important molecules. Hemoglobin and myoglobin are heme-containing proteins that are involved in the transport and storage of oxygen. Hemoglobin is the primary protein found in red blood cells and represents about two thirds of the body's iron. The vital role of hemoglobin in transporting oxygen from the lungs to the rest of the body is derived from its unique ability to acquire oxygen rapidly during the short time it spends in contact with the lungs and to release oxygen as needed during its circulation through the tissues. Myoglobin functions in the transport and short-term storage of oxygen in muscle cells, helping to match the supply of oxygen to the demand of working muscles.

Cytochromes are heme-containing compounds that are critical to cellular energy production and therefore, life, through their roles in mitochondrial electron transport. They serve as electron carriers during the synthesis of ATP, the primary energy-storage compound in cells. Cytochrome P450 is a family of enzymes that functions in the metabolism of a number of important biological molecules, as well as the detoxification and metabolism of drugs and pollutants. Nonhaeme iron-containing enzymes, such as NADH dehydrogenase and succinate dehydrogenase, are also critical to energy metabolism.

Catalase and peroxidases are heme-containing enzymes that protect cells against the accumulation of hydrogen peroxide, a potentially damaging reactive oxygen species (ROS), by catalyzing a reaction that converts hydrogen peroxide to water and oxygen. As part of the immune response, some white blood cells engulf bacteria and expose them to ROS in order to kill them. The synthesis of one such ROS, hypochlorous acid, by neutrophils is catalyzed by the heme-containing enzyme myeloperoxidase.

Inadequate oxygen (hypoxia), such as that experienced by those who live at high altitudes or those with chronic lung disease, induces compensatory physiologic responses, including increased red blood cell formation, increased blood vessel growth (angiogenesis) and increased production of enzymes utilized in anaerobic metabolism. Under hypoxic conditions transcription factors, known as hypoxia inducible factors (HIF), bind to response elements in genes that encode various proteins involved in compensatory responses to hypoxia and increase their synthesis. Recent research indicates that an iron-dependent propyl hydroxylase enzyme plays a critical role in regulating HIF and consequently, physiologic responses to hypoxia. When cellular oxygen tension is adequate, a propyl hydroxylase enzyme in an iron-dependent process that targets HIFa for rapid degradation modifies newly synthesized HIFa subunits. When cellular oxygen tension drops below a critical threshold, propyl hydroxylase can no longer target HIFa for degradation, allowing HIFa to bind to HIFa and form an active transcription factor that is able to enter the nucleus and bind to specific response elements on genes.

Ribonucleotide reductase is an iron-dependent enzyme that is required for DNA synthesis. Thus, iron is required for a number of vital functions, including growth, reproduction, and healing, and immune function.

Iron response elements are short sequences of nucleotides found in the messenger RNA (mRNA) that codes for key proteins in the regulation of iron storage and metabolism. Iron regulatory proteins (IRP) can bind to iron response elements and affect mRNA translation, thereby regulating the synthesis of specific proteins. It has been proposed that when the iron supply is high, more iron binds to IRPs and prevents them from binding to iron response elements on mRNA. When the iron supply is low, less iron binds to IRPs, allowing increased binding of iron response elements. Thus, when less iron is available, translation of mRNA that codes for the iron storage protein, ferritin is reduced because iron is not available for storage. Translation of mRNA that codes for the key regulatory enzyme of heme synthesis in immature red blood cells is also reduced to conserve iron. In contrast, IRP binding to iron response elements in mRNA that codes for transferrin receptors inhibits mRNA degradation, resulting in increased synthesis of transferrin receptors and increased iron transport to cells.

L-carnitine

L-carnitine is a derivative of the amino acid, lysine. Its name is derived from the fact that it was first isolated from meat (carnus) in 1905. Only the L-isomer of carnitine is biologically active. L-carnitine appeared to act as a vitamin in the mealworm (Tenebrio molitor), and was therefore termed vitamin BT. Vitamin BT, however, is actually a misnomer because humans and other higher organisms can synthesize L-carnitine. Under certain conditions, the demand for L-carnitine may exceed an individual's capacity to synthesize it, making it a conditionally essential micronutrient.

L-carnitine is synthesized primarily in the liver but also in the kidneys, and then it must be transported to other tissues. It is most concentrated in tissues that use fatty acids as their primary dietary fuel, such as skeletal and cardiac (heart) muscle. In this regard, L-carnitine plays an important role in energy production by chaperoning activated fatty acids (acyl-CoA) into the mitochondrial matrix for metabolism and chaperoning intermediate compounds out of the mitochondrial matrix to prevent their accumulation.

L-carnitine is required for mitochondrial beta-oxidation of long-chain fatty acids for energy production. Long-chain fatty acids must be in the form of esters of L-carnitine (acylcarnitines) in order to enter the mitochondrial matrix where beta-oxidation occurs. Proteins of the carnitine-acyl transferase family transport acylcarnitines into the mitochondrial matrix. On the outer mitochondrial membrane, carnitine-palmitoyl transferase I (CPTI) catalyzes the transfer of long-chain fatty acids into the cytosol from coenzymeA (CoA) to L-carnitine, the rate limiting step in fatty acid oxidation. A transporter protein called carnitine:acylcarnitine translocase (CACT) facilitates the transport of acylcarnitine esters across the inner mitochondrial membrane. On the inner mitochondrial membrane, carnitine-palmitoyl transferase II (CPTII) catalyzes the transfer of fatty acids from L-carnitine to free CoA in the mitochondrial matrix, where they are metabolized through beta-oxidation, ultimately yielding propionyl-CoA and acetyl-CoA.

Regulation of Energy Metabolism through Modulation of Acyl CoA:CoA Ratio

CoA is required as a cofactor for numerous cellular reactions. Within the mitochondrial matrix, carnitine acetyl transferase (CAT) catalyzes the trans-esterification (transfer) of short- and medium-chain fatty acids from CoA to carnitine. The acylcarnitine esters can then be exported from the mitochondria via CACT, and the resulting free CoA can participate in other reactions. For example, pyruvate dehydrogenase (PDH) catalyzes the formation of acetyl CoA from pyruvate and free CoA. Acetyl CoA, in turn, can be oxidized to produce energy (ATP) in the tricarboxylic acid (TCA) cycle. Carnitine facilitates the oxidation of glucose by removing acyl groups generated by fatty acid beta-oxidation and freeing CoA to participate in the PDH reaction.

L-tyrosine

L-Tyrosine is a nonessential amino acid and it's nutrient role is as a neurotransmitter, which act as chemical messengers to the body's 100 billion (or more) of nerve and brain cells. L-Tyrosine helps form three important neurotransmitters: serotonin, dopamine, and norepinephrine; these are responsible for functions like memory, mood, appetite, and muscular coordination. Clinical studies have shown that L-Tyrosine supplements help with depression, anxiety, and heighten the mood in just a matter of a few weeks. It also helps fight fatigue and irritability.

Possible benefits:

Reduces anxiety and helps with depression

Elevates the mood and increases sense of well-being

Increases alertness and arousal

Facilitates motor function of the body and muscular coordination

Fights fatigue

Helps regulate release of hormones

Magnesium

Magnesium is involved in more than 300 essential metabolic reactions.

The metabolism of carbohydrates and fats to produce energy requires numerous magnesium-dependent chemical reactions. Magnesium is required by the adenosine triphosphate (ATP) synthesizing protein in mitochondria. ATP, the molecule that provides energy for almost all metabolic processes, exists primarily as a complex with magnesium (MgATP).

Magnesium is required at a number of steps during the synthesis of nucleic acids (DNA and RNA) and proteins. A number of enzymes participating in the synthesis of carbohydrates and lipids require magnesium for their activity. Glutathione, an important antioxidant, requires magnesium for its synthesis.

Magnesium plays a structural role in bone, cell membranes, and chromosomes.

Magnesium is required for the active transport of ions like potassium and calcium across cell membranes. Through its role in ion transport systems, magnesium affects the conduction of nerve impulses, muscle contraction, and the normal rhythm of the heart.

Cell signaling requires MgATP for the phosphorylation of proteins and the formation of the cell signaling molecule, cyclic adenosine monophosphate (cAMP). cAMP is involved in many processes, including the secretion of parathyroid hormone (PTH) from the parathyroid glands (see Vitamin D and Calcium for additional discussions of the role of PTH).

Calcium and magnesium levels in the fluid surrounding cells affect the migration of a number of different cell types. Such affects on cell migration may be important in wound healing.