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Magnesium is an essential mineral used in over 300 biochemical reactions in the human body. Adults store about 25 grams of magnesium, with 1% being found in the blood and 60% found in the bones. Magnesium is used by the body in the process of creating energy and ATP from carbohydrates and fats and is required for synthesis of DNA and RNA, active transport of potassium and calcium, cell- signaling and communication, and glutathione metabolism. Studies with cardiovascular disease, migraine headaches, endothelial dysfunction, and asthma, have all shown mixed results due to variation in study design. Magnesium improves muscle performance in older individuals and lowers serum catecholamine excretion(7,20). and reduced magnesium intake has been shown to be associated with depression in communal living (16).
Magnesium is found in the highest levels in halibut, some tree nuts, soy, leafy green vegetables, rice, oats, and potatoes. The tolerable upper limit is listed at 350 mg per day for adults over age 19 but the RDA is 420 mg per day for men over age 30 and 320 mg per day for women over 30. The absorption of magnesium is reduced by fiber intake and improved by ingestion of protein. Low HCL levels in the stomach have been associated with low levels of beneficial gut bacteria which are crucial for absorption of magnesium.
Selenium is an essential trace element that humans require for selenium-dependent enzymes called Selenoproteins. Selenoproteins are enzymes that are used in specific metabolic reactions and of the 25 that have been identified, only 12 have known functions. Five of these proteins are selenium-containing enzymes that participate in the reduction of glutathione, the body’s most important antioxidant. Two of them are used to reduce methionine, a sulfur-based compound that is used to synthesize glutathione. It is through the synthesis of glutathione that selenium has also been found to be neuro-protective, (1,6) and several studies have shown that low selenium levels are associated with cognitive impairment, depression anxiety and hostility (29) and one study showed that low plasma selenium was associated with senility and accelerated cognitive decline (13). The RDA for selenium is 55 mcg per day for men and women age 19 and older and the Tolerable Upper Limit is 400mcg
Ascorbic acid, or Vitamin C is an essential nutrient required for the synthesis of muscle, ligaments and collagen and blood vessels. In addition it’s metabolic functions include the regeneration of Vitamin E, and is used as an antioxidant to protect the tissues against oxidative stress. The Linus Pauling Institute at Oregon State University found in a large collection of studies that 100mg of vitamin C per day have shown benefit in and reducing incidence of and mortality from heart disease, stroke, and cancer. In addition, an intake of 500mg of Vitamin C has been shown to decrease mild or moderate hypertension(40). Perhaps it’s most important role in relation to brain function includes it’s ability to aid in the conversion of dopamine to norepinephrine and epinephrine – both of which play a huge role in neuro-modulation.
Pantothenic acid or vitamin B5 is an essential nutrient found in many plants and animals in the form of Coenzyme A. Coenzyme A is an intermediate in the Krebs cycle and is essential for the production of ATP, the energy currency of cellular metabolism. Pantothenic acid is highly concentrated in the adrenal glands and is necessary for the production of steroid hormones and acetylcholine an important neurotransmitter. Pantothenic acid deficiency has been shown to result in poor adrenal function and experimentally induced deficiency in humans results in insomnia, leg cramping, numbness in the hands and feet, mental depression and fatigue, decreased antibody function, postural hypertension, GI disturbance and upper respiratory infections.
Foods with a high amount of pantothenic acid include fish, chicken, eggs milk and yogurt. The adequate intake of B5 is 5 mg per day for adults over the age of 19.
Pyridoxine HCL (B6)
Pyridoxine (B6) is a water soluble vitamin that is essential to the human diet. It is found in various foods, the highest of which is bran cereal. The most active form of pyridoxine in the human body is pyridoxal-5-phosphate (PLP). PLP reacts with approximately 100 enzymes that catalyze various metabolic reactions throughout the body including the transfer of sulfhydryl groups from methionine to serine to form cysteine. PLP has also been shown to bind to estrogen, progesterone, and testosterone receptors and inhibit the effects of those hormones. In the brain PLP aids in the synthesis of dopamine, norepinephrine, serotonin, GABA and histamine. (5) Individuals showing severe PLP deficiency produce symptoms of depression, irritability, and confusion. Those most at risk for severe deficiency are alcoholics but many compounds have been shown to antagonize or increase the requirement for B6 including food additives, petrochemical derivatives, birth control pills, PCB’s, hydrazine, L-dopa, and fruit-ripening agents. (25) Potential drug interactions include, phenobarbitol, phenytoin, and L-dopa.
Cobalamin or vitamin B12 is an essential vitamin that is synthesized only in bacteria but is found in meat, poultry, fish and to lesser extent, milk. It is highly concentrated in liver and is used in the enzyme methionine synthase which is used to convert homocysteine to methionine. Methionine is converted to s-adenosyl methionine or SAM-e which is an important methyl donor for multiple metabolic reactions including the synthesis of DNA and RNA. Elevated levels of homocysteine are associated with an increase in cardiovascular disease.
The active form of B12 is methylcobalamin. Supplementation of B12 is available in the form of methylcobalamin, hydroxycobalamin, and the synthetic form cyanocobalamin. Vitamin B12 deficiency is a hotly debated topic and is likely caused by inefficient absorption of B12 due to conditions such as, pernicious anemia, atrophic gastritis, and drug interactions caused by proton pump inhibitors omeprazole, lansoprozole, chloramphenicol cholestyramine, neomycin, colchicine, and Metformin. Deficiency can also be caused by a lack of intake due to vegetarian and vegan diets. Deficiency symptoms may include depresssion, fatigue, glossitis, neuropathy, elevated homocysteine levels, megaloblastic anemia, and GI symptoms.
Folic Acid (5 MTHF)
Folic acid is a synthetic, water soluble B vitamin that exists in nature in the form of folate. Folates are used in the body to transfer and deliver one-carbon groups in nucleic acid synthesis and methionine production from homocysteine. With a limited intake of dietary or supplemental folate or genetically-based methylation defects, individuals are at risk for developing elevated homocysteine and increased risk for cardiovascular disease, macrocytic anemia, depression, fatigue, weakness, shortness of breath and many other problems. Alcohol and several medications including Methotrexate, Triampterene, Trimethoprim, Metformin, Sulfazine, and Barbiturates, interfere with or deplete body stores of folate. Individuals taking these medications need to consider their intake of folate to avoid long-term depletion and risk for some of the conditions associated with folate deficiency. It is well-known that a folate deficiency is associated with an increase risk for neural-tube defects in pregnancy but lesser known associations with colorectal cancer and Alzheimer’s disease indicate folate plays a critical role in metabolic function. Toxicity levels of folate have not been established but supplemental intake of folic acid or folate can mask a B12 deficiency, and therefore levels of B12 and folate should be monitored in individuals testing positive for macrocytic anemia.
Vitamin D has become the most well-known, and talked-about vitamin in health circles today. Recent research have shown that vitamin D performs multiple functions throughout the body that are so important, that testing every individual for deficiency has become commonplace.
Vitamin D is obtained by the body through the conversion from D2 to D3 through sunlight and through absorption through the Gi tract from the diet. In the kidneys, Vitamin D3 is converted to a more potent form called 1,25-dihydroxyvitamin D. More than 50 genes in tissues throughout the body are known to be regulated by 1,25-dihydroxyvitamin D (4). This form of vitamin D is a potent immune system modulator, regulates calcium balance, cell differentiation, insulin secretion and blood pressure regulation. Vitamin D’s association with depression has been theorized to be due to immune system regulation of cytokine production and many studies have proven that increased levels of serum vitamin D3 contribute to improvement of symptoms of depression.
In temperate areas where sunlight is less available and in populations that tend to obtain less sunlight, vitamin D supplementation is recommended. There is much debate regarding the appropriate levels of supplementation needed to achieve freedom from pathological conditions associated with vitamin D3 deficiency. The recommended daily allowance of vitamin D3 is 600 IU per day. Recent studies support the use of up to 2000IU per day. Since vitamin D3 intake below 10000IU will not likely elevate blood levels above the safe recommended level of 50 ng/ml, individuals are likely safe taking any amount below that level. Recent advances in testing protocols and research findings have supported a minimum of 32 ng/ml up to 50 ng/ml as sufficient to avoid symptoms associated with deficiency.(15,39)
L-theanine is an amino acid found in green tea. It is an analog of glutamic acid and glutamate and readily crosses the blood brain barrier where it acts as a psychoactive compound to modify glutamate receptors, modulate serotonin, increase GABA, and dopamine(28,38). It has also been found to increase alpha waves which are responsible for the speed of nerve transmission in association with acetylcholine(10,11). In one study L-theanine was shown to attenuate short-term sympathetic nervous system response in individuals exposed to experimental stress(19). L-theanine in one study was determined to be safe up to 4000mg/kg/day for 13 weeks in animal models (2) . In clinical practice doses of 100mg per day have been successfully used to reduce symptoms of anxiety and perceived stress.
Methionine is a sulfur-based essential amino acid found in high concentrations in eggs, fish, meat poultry, brazil nuts, and sesame seeds. It is an intermediate in the biosynthesis of cysteine, carnitine, taurine, lecithin, phosphatidylcholine, and the methyl donor s-adenosylmethionine (SAM-e) and ultimately contributes to the production of glutathione, an important antioxidant. Low protein diets and those heavily dependent on soy for their protein are at risk for the problems that involve this pathway. On a functional level, methionine helps prevent fat accumulation in the liver, and aides in the detoxification of metabolic wastes and toxins. Recommended doses of supplemental methionine range from 500mg to 4000mg per day and toxicity levels have not been established.
5-hydroxytryptophan (5HTP) is an immediate precursor to serotonin, a neurotransmitter found in both the central and peripheral nervous systems. In the brain, serotonin is used as a chemical messenger to adjacent nerve cells and as a precursor to melatonin, the biochemical in charge of sleep. Through these mechanisms serotonin drives the recovery process in the body by initiating delta waves allowing us to rest, regenerate and establish a sense of well-being.
5HTP is readily absorbed and crosses the blood-brain barrier resulting in availability in the CNS. Once it is absorbed, 5HTP is exposed to the decarboxylase enzyme and used in the production of serotonin and melatonin. In one study, supplementation with 5HTP has resulted in dose-dependent bio-availability of 48-84% with a mean of 69% +/- 4.7%, and a relatively slow absorption rate of 1.8 to 3.3 hours(24). The individual variation in bio-availability and absorption time is likely due to the individual needs as reflected by studies involving kidney regulation of serotonin and dopamine.
5HTP has been used in many small trials as a stand-alone treatment and with SSRI’s as a treatment for depression, migraine headaches, insomnia, sleep terrors and for psychological conditions relating to relationships (3,4,8,14,36). Efficacy is varied and this is likely due to the multifactorial mechanisms involved in the pathways that regulate these processes. Hinz et al, in various clinical trials have found that the use of 5HTP by itself is marginally effective when used for depression, but when used in combination with compounds that support other brain processes, is highly effective (14). Other trials have shown the relationship between dopamine and serotonin and the results support that supplementation with 5HTP can affect and be affected by compounds that increase dopamine(23).
The LD50 in mice was shown to be 200mg/kg in one study but supplemental doses in humans are usually kept below 500mg per day.
L-tyrosine is a non-essential amino acid derived from the essential amino acid phenylalanine. It is found in soy, poultry. fish peanuts, almonds, avocados, milk, cheese, yogurt, cottage cheese, lima beans, pumpkin seeds and sesame seeds. In the adrenal glands, tyrosine is converted to norepinephrine and epinephrine and supplemental tyrosine increases these plasma catecholamines. In the brain tyrosine is the precursor to the neurotransmitters dopamine and norepinephrine and has been shown in mice to replete those catecholamines(30). Tyrosine is also used in the body as a building block for thyroid hormone and melanin. Some have suggested that tyrosine intake be limited to 12000 mg per day. The LD50 for tyrosine has not been established.
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