Vitamin D: refers broadly to the organic compounds named vitamin D2 (ergocalciferol), 25-hydroxyvitamin D2, 1?, 25-dihydroxyvitamin D2 and vitamin D3 (cholecalciferol), 25-hydroxyvitamin D3, 1?, 25-dihydroxyvitamin D3.  Vitamin D is not a true vitamin because it can be synthesized by humans with adequate sunlight exposure. The effects of vitamin D on bone mass are supported in the literature. It is likely that the major source of vitamin D for human is not dietary, but results from its manufacture by a chemical photolysis reaction in skin. Vitamin D3 itself is a biologically inert molecule. It must be activated by 25-hydroxylation in the liver to produce the major circulating form of vitamin D, 25-hydroxyvitamin D3. However, 25-hydroxyvitamin D3 is also biological inactive at physiologicl concnetrations, and it is finally activated in the proximal convoluted tubule cells of the kindey to produce 1alpah,25-(OH)2D3 (also called calcitriol).

Functions: The Vitamin D hormones have essential roles in human health which are mediated by the intracellular VDR. In particular, the Vitamin D hormones regulate blood calcium levels by controlling intestinal absorption of dieatry calcium and reabsorption of calcium by the kidenyes. The hormones also participate in the regulation of cellular differentation and grwoth and normal bond formation and metabolism. 

Vitamin D is linked to lower risks of colon, breast, prostate and ovarian cancers. People with higher levels of Vitamin D are also less likely to suffer autoimmune diseases, including type 1 diabetes and MS. Vitamin D also helps mobilize and modulate the immune system by encouraging cells to self-destruct before becoming malignant. Tissues throughout the body have receptors for vitamin D which would seem to indicate a purpose for vitamin D.

Vitamin D, especially its active form calcitriol can affect phosphate homeostasis by directly sitmulaitng interstinal absorption of phosphate. In addition, vitamin D enhances bone resorption through mobilization of calcium and phosphate into the plasma.

Vitamin D Deficiency: Vitamin D deficiency can lead to secondary hyperparathyroidism. It is characterized by abnormally elevated blood levels of parathyroid hormone (PTH) and, in the absence of early detection and treatment, it becomes associated with parathyroid gland hyperplasia and a constellation of metabolic bone diseases. It is a common complication of chronic kideny disease (CKD).

Vitamin D deficiency may also underlie a vulnerability to infections by the microbes that a natural antimicrobial, called cathelicidin, targets.

Regulation: Blood levels of 1,25-dihydroxyvitamin D are preciesly regulated by a feedback mechanisms which involves PTH. The renal 1?-hydroxylase (or CYP27B1) is stimulated by PTH and inhibited by 1,25-dihydroxyvitamin D. When blood levels of 1,25-dihydroxyvitamin D fall, the parathyroid glands sense this change via intracellular Vitmain D receptors and secrete PTH. The secreted PTH stimulates expression of renal CYP27B1 and, thereby, increases production of Vitmain D hormones. As blood concentrations of 1,25-dihydroxyvitamin D rise again, the parathyroid glands attenuate further PTH secretion. As blood PTH levels fall, renal production of Vitamin D hormones decreases. (see US 2009/0209501A1)

Recommended daily allowance of vitamin is 1000 units per day. This can be reached simply by 10 minutes out in the sun with no . So if it is currently believed to be beneficial to include at least some of your activity outside each day.

Vitamin C is water soluble and acts as a cofactor in hydroxylation reactions, which are required for collagen synthesis. It is an essential water-soluble nutrient which primarily exerts its effect on host defense mechanisms and immune homeostatsis by being the most important physiological antioxidant. It is also involved in a variety of other biochemical functions such as hormone synthesis, wound healing, and iron absorption.Vitamin C has been shown to inactivate a host of viruses upon exposure. It has been implicated as hoaving both a preventative and a therapeutic role in a variety of diseases including scurvy, viral infections and common cold, cancer and atherosclerosis.It also protects neutrophils from oxidation.

Part of vitamin C’s protective benefit is due to its antioxidant action. Oxidative stress increases the antioxidant requirements of the white blood cell macrophages and lymphyoctes. Vitamin C supplementation increases antioxidant glutathione concentration in lymphocytes and normalizes monocyte adhesion to endothelial cells. Oxidative damage plays a key role in endotoxin (LPS)-induced spesis leading to an inappropriate activation of the transcription factor NFkB and, subsequently, to an overexpression of inflammatory proteins. Vitamin C may protect from dysregulation of the immune-inflammatory response by its antioxidant properties. Long used against the common cold, vitamin C has shown mixed results. However, a 2002 study involving 180 British subjects found supplementation could prevent the common cold, as well as limit severe symptoms and shorten the duration.

Fourt independent double-blind studies have reported that ascorbic acid reguraly ingested in dialy amounts more than 100 mg decreases the incidence as well as the severity of colds in comparison with a placebo.

During active infection this nutrient is quickly depleted thus increasing the body’s need. The current RDI is 60 mg.

Foods Rich in Vitamin C: Food sources include citrus fruits, strawberries, mellons, tomatoes, broccoli and peppers (especially red). The body’s rate of absorption of Vitaimn C is often not greater than 1 g hour, so divided doeses are important. Second, if taking large doeses, rebound scurvy can develop if the individual abruptly stops taking the vitamin.

The soybean plant (Glycine max) belongs to the legume family. It is able to utilize the nitrogen of the air through the action of bacteria on its roots. The protein content of the seed is about 40%. After the hulls and the oil are removed, the remaining defatted flake, which is the starting material for most commercial protein ingredients, has a protein content of about 50%. Soy protein can enhance the nutrional quality of other vegetable proteins. For example, soy protein products contain a level of lysine which exceeds human requirements and thus can correct lysine deficiency found in some protein containing grains, such as wheat or corn. Studies have shown that soy protein products are comparable in digestibility to other high quality protein sources such as meat, milk, fish and eggs. Many applications for soy protein products involve combinations with creal grains and/or alternate protein sources. Soy protein amino acid profiles (fich in lysine, limiting in sulfur amino acids) fit nicely with grain proteins (limited in lysine, rich in sulfur amino acids). (“Soy Protein Products, Characteristics, nutritional aspects and utilization. A publication of AOCS, ISBN 1-893997-28-8). 

Benefits of Soy Protein on Human Diseases

There is ample evidence that protein products have a positive influence on human disease such as cardiovascular disease (CVD) and several types of cancer. In addition, soy protein products can make a significnant contribution to weight reuction, mainly by providing essential high quality protein in a concentrated form for specially designed, low calorie/high nutrient desnity meals. (“Soy Protein Products, Characteristics, nutritional aspects and utilization. A publication of AOCS, ISBN 1-893997-28-8).

Soy Products

Soy milk: is prepared by an aqueous extract of the whole soybean.

Soy sauce: is made by fermentation of a combination of soybeans and creals, usually wheate. 

Tempeh: is preapred by cooked soybeans fermented by the mold Rhizopus oryzae (protein continet about 20% on a wet basis and 50% after drying). It is used in Indoesian cusine. 

Tofu (soy curd) is made by coagulation of soy milk. Tofu curd contains 88% moisture, 6% protein, and 3.5% oil. Tofu can be frozen, aged and drited (56% protein). (“Soy Protein Products, Characteristics, nutritional aspects and utilization. A publication of AOCS, ISBN 1-893997-28-8).

Selenium is an integral part of more than about 30 known proteins. These proteins are called selenium-containing proteins or selenoproteins, of which about 15 have been purfied to allow characterization of their biological function. Selnium is incorporated into these selenoproteins as the 21st amino acid, selenocysteine.

In addition to incorporation as selenocysteine, selenium can replace sulfur in methionine, forming selenomethionine. This compound can be incorproated non-specifically into proteins in place of met. Finally, selenium can be tightly bound by certain proteins, known as selenium-bnding proteins, to distinguish them from true selenoproteins. Selenium is found in human and animal tissues as L-selenomethionine or L-selenocysteine.

Selenoproteins

Selenoproteins are comprised of four glutatione peroxidases, three idothyronine deiodinases, three thioredoxin reductases, selenoprotein P, selenoprotein W and selenophosphate synthetase. Over half of the Se in plasma is in the form of selenoprotein P.

Selenoproteins perform a variety of physiological role. The glutatione peroxidases, and possibly selenoprotein P and selenoprotein W, are antioxidant proteins that reduce potentially damaging reactive oxygen species (ROS) such as hydrogen peroxide and lipid hydroperoxides, to harmless products – water and alchols- by coupling their reduction with oxidation of glutathione.

Glutathione in its reduced form (GSH) is the single most important protective and regulatory antioxidant in cells. As it is oxidized it becomes oxidized glutathione (GSSG), and the intracellular ratio of GSH:GSSG is reportedly a very good measure of the cell’s overall antioxidant status. T helper cells infected with HIV-1 reportedly deterioated in GSH status and progressively lost their functional capacity.

Only a few mammalian selenoproteins have well understood roles; these include several forms of glutathione peroxidase (GPX) and the type I 5–iodothyronine deiodinase involved in conversion of T4 thyroid hormone to T3. Glutathione Peroxidase 1 (GPX1 or cGPX) is one of the most thoroughly studied selenoproteins. It catalyzes glutathione-dependent reduction of hydrogen peroxide and various organiz hydroperoxides. The enzyme is a homotetramer of ~22kd subunits and it is located in the cytosol.

Estimates of the total number of selenoproteins encoded in the genomes of mammals range from 25 to 100. These estimate are based on 75Se-labeling experiments, which detect selenoprotein spots on 2D gels.

Selenocystein: biosynthesis and characterization 

Selenocystein (Sec) is recognized as the 21st amino acid, as it has its own codon and selenocysteine-specific ciosynthetic and insertion machinery. The 3′ untranslated region of all mammalian selenoprotein mRNAs contains a region of conserved secondary structure, the Sec insertion sequence (SECIS element). This element is required for reocgnition of UGA condos as Sec, and serves as the binding site of the SECIS element binding protein-2. SBP2 binds to a conserved, non-Watson-Crick base-paired region in the stem of the SECIS element and remains bound through multiple cycles of selenoprotein translation. SBP2 also binds to a selenoprotein-specific elongation factor, eEFSec (rather then the standard elongation factor, eEFIA) which exhibits specificity for both the unique tRNA structure and the amino acid. Recruitment of the Sec-tRNA-EFsec complex to the ribosome occurs via its interaction with the SECIS binding protein 2, a protein exhibiting specificity for the SECIS elements in selenoprotein mRNAs.

The tRNA is first aminoacylated with serine, which serves as the backbone for the biosynthesis of Sec. Sec tRNA is therefore designated tRNA[Ser]Sec. The Sec condon is deciphered by a unique tRNA possessing a UCA anticodon. In short, in the presence of a downstream stem-loop structure, the UGA condon in mRNA, instead of behaving as a stop condon, specifies the insertion of a selenocysteine moeity in the protein synthesis to give a selenoprotein. In summary, a unique tRNA, designated tRNA[Ser][Sec] is charged with L-serine, which is then converted through at least two steps to selenocysteine. With the aid of a unique translation factor, the selenocysteinyltRNA[Ser][Sec recongizes specific UGA condons in mRNA to insert selenocysteine into the primary structure of selenoproteins.

In prokaryotes, the biosynthesis of Sec is as follows: Sec tRNA is first aminoacylated with serine, the serine moiety is in turn modified to an aminoarcrylyl interdiate onto RNA by Sec synthase and then the itnermediate serves as the accepter for activated selenium. The selenium donor is selenophosphate which is synthesized by selenophosphate synthetase. Many of these steps are apparently similar in mammals.

Nature may have taken advantage of utilizing Sec at critical sites in certain enzymes due to the unique redox proterties of selenium. Although Sec is structurally similar to , selenium is a better nucleophile than sulfur and selenocysteines are ionized at physiological pH, while cysteins typically are protonated.

The approach of identifying Sec insertion sequence elements in nucleotide databases has been applied in the HIV genome. SECIS elements are characterized by the presence of a highly conserved ATGAN[10-12 nucleotides]AAN[16-26 nucleotides]NGAN sequence, which forms stem-loop structures with AAN located in the loop, and TGAN and NGAN forming the non-Watson-Crick quartet interaction.

Recommended Dietary Allowance (RDA) 

A daily Se intake of up to 400 ug is considered safe and clinical manifestations of Se intoxication (selenosis) in humans appear only when it exceeds 900 ug. The prinicipal indicator of the amount of Se in the organism is its blood level. Blood contains Se mainly in the form of GPx. The optimal activity of of this anti-oxidative enzyme can be reached only when the level of Se in serum or plasma is at least 90 ug/L.

Selenite (inorganic form) and selenomethionine (organic form) are chemical forms of selenium mostly used in supplments and fortified food. Selenomethionine is generally considered to be the best absorbed and utilized form of selenium. It is also available in high selenium yeasts. Most of the selenium in these yeast is in the form of selenomethionine. Selenium has been supplied both as inorganic forms such as selenate or selenite and organic forms such as selenomethionine or as selenium yeast.

Where do you find Selenium? Foods which are good sources of selenium

Se is highly absorbable. It occurs naturally in plants as selenomethionine, Se-methyl-selenomethionine, selenocysteine, and selenocystine. Selenite (commercially available as sodium selenite) is greater than 80-percent bioavailable and selenomethionine or selnate can be greater than 90% bioavailable.

Absorption from food is also efficient. Se is mainly found in wheat and other cereals, beef and pultry, fish and other seafood. Human food contains Se in the form of selenoamino acids, selenometionine and selenocysteine (considered the 21st amino acid). Selemonethionine is the major organic selno-cpound in creal grains, grassland legumes and soybeans, as well as in selenium-enriched eyast used for slenium supplementation.

Brazil nuts are rich in selenium.

Immune System Effects of Selenium

Most, if not all, of the beneficial effects of selenium on human health are medaited by selenoproteins.

Lymphocytes from subjects supplemented with Se (as Na2SeO3) at 200 ug/d showed an enhanced response to antigen stimulation and an increased ability to develop into cytotoxic lymphocytes and destroy tumour cells. NK activity as also increased.

The main mechism by which Se boosts cell immunity is the stimulation of expression of the high-affinity IL-2 receptor on activated T lymphocytes and NK cells. This facilitates their interaction with IL-2, which is crucial for their clone expansion and differentiation into CTL.

Se also has anti-oxidative and anti-inflammatory effects that derive from the ability of Se (especially its key anti-oxidative compound GPx) to reduce hydrogen preroxid and hpspholipid hydroperoxides and thereby stop the production of free radicals andr eactive forms of oxygen.

The mRNA of several T cell associated genes (IL2 receptor alpha subunit, CD4) have the theoretical capacity to encode functional selenoproteins, suggesting that the roles of Se in the immune system may be quite diverse. HLA-DR is an important marker for activated T cells. Thus, if the gene for its invariant chain also encodes a selenoprotein with 10 SeC residues (suggesting a substantial Se requirement), Se may be an esential lymphocyte nutritional factor that plays a significant role in T cell function and proliferation. This is consistent with reports that Se supplementation in culture increases the cytotoxicity of killer T cells as well as the proliferation of T cells in response to mitogens and antigens, whereas Se deficiency does the opposit and is associated with impaired immune function.

Se may be able to reverse age related declines in immune responses in the elderly. In a group of 22 institutionalized elderly subjects supplemented with 100 ug Se-enriched yeast or placebo for 6 months, response to mitogen challenge in those receiving the Se was restored to the level of that in healthy young individuals.

Effect on Viral Infection: Se deficiency induces progression of some viral diseases not only by reducing the function of the IS, but also by increasing the virulence of the infectious agents. Se also appears to be a key nutrient in counteracting certain viral infections. In Se-deficint host harmless viruses can become virulent. A case in point for this was a study using a mouse model. Coxsackieviruses are small RNA enteroviruses in the Picornaviridae which are known to infect the heart and can cause myocarditis, or inflamatory heart disease. Mice are well-established models for coxsackievirus-induced myocarditis and develop a pattern of heart inflammation similar to that found in human.Both myocarditic and amyocarditic mice are available.

In this study, mice were fed a diet deficient in Se begining at the time of weaning. After a period of 4 weeks, glutathione peroxide activity, a marker of Se status, was 1/5 of the activity in Se-adequate mice. Se-deficient an d Se-adequate mice were infected with a normally amyocarditic strain of coxsackievirus B 3 (CVB3/0). At various times post infection, the mice were killed and tissues removed for study. Se-adequate mice did not develop myocarditis when infected with the amyocarditic strain of virus. However, the Se-deficient animals did develop a moderate level of myocarditis, characterized by inflammatory foci scattered through the myocardium. Heart virus titers also revealed that the De-deficient mice had a 10-100 fold higer levels of virus in the heart post infection compared with the Se-adequate mice. The immune response of the Se-deficient mice was also found to be altered. Although the production of neutralizing antibody resposnes was not affected, the proliferative response of T cells to both mitogen and antigen were decreased. Because inflammation is the hallmark of coxsakieviru-indued myocarditis, expression of mRNA for several inflammatory chemokines was examined. MCP-1 was highly expressed at day 10 in the De deficient animals as compared with the Se-adequate animals which could explain the inflammation found in the infected Se-deficient mice. In addition, expression of mRNA for y-interferonwas greatly decreased in the Se-deficient mice.

This important study meant that either an altered immune response might have been responsible for the myocarditis that developed in the Se-deficient mice infected with an amyocarditic strain of CVB3 or the viral pathogen might have been affected or both. To determine if host factors alone were responsible for the devleopment of myocarditis in the Se-deficient CVB3/0 infected mice, a passage experiment was performed. Se-adequate and Se-deficient mice were infected wtih CDB3/0. Seven days later, their hearts were removed and the virus isolated. This isolated virus was then passed back into Se-adequate mice. If the inductin of myocarditis was due solely to host conditions, then the Se-adequate mice should not devlop myocarditis from infection from either the virus isolated from the Se-adequate or deficient mice. Surprisingly however, Se-adequate mice infection with the virus isolated from Se-deficient aniamls developed myocarditis wehreas the Se-adequate mice infected with the Se-adeqaute passed virus did not. These resutls strongly suggested that the virus that replicated in the Se-deficient mice underwent a genomic change. To confirm that a change in viral genome had occured, viruses recovered from both Se-adequate and Se-deficient mice were sequenced. The sequence of the virus recvoered form Se-adequate mice was identical to the orignal stock virus used to inculate the mice. However, the sequence of the virus recovered from Se-deficient mice had 6 point muations. Thus replication of coxsackievirus in a Se-deficient host leads to changes in the viral genome. Once these genomic changes occur, even mice with normal nutriture are susceptible to the newly pathogenic strain of virus.

A second case in point is a similar study done with influenza virus. Influenza virus is a segmented RNA virus in the Orthomyxoviridae family. These viruses are responsible for many deaths each year and older adults are particularly susceptible. Influenza viruses alter their surface proteins in order to escape early detection by the immune system. To determine if a deficiency in Se affects the pathogenicity of an influenza virus, Se-deficient and Se-adquate mice were infected with a mild strain of influenza (A/Bangkok/1/29). At various times post infection, mice were killed and tissues harvested. Again, Se-deficient mice developed much more severe lung inflammation post influenza infection when compared with the infected Se-adequate mice. Se-deficient mice also had decreased percetnages of CD8+ cells infiltrating the lungs, compared with Se-adequate mice. In the draining lymph nodes, Se-deficient mice had an increased in the production of proinflammatory cytokines and chemokines. In addition, the Th2-like as opposed to the more Th1 like found in infected Se adequate animals. What was even more interesting, sequencing of the mRNA segments that code for viral surface prtoeins (HA-hemagluttinin and NA-neurominidase) revelealed little diference between Se deficient and adequate naimals. However, the mRNA that codes for teh amtrix protein revealed 29 nucleotide chagnes of which sex led to amino acid changes. Virus recovered from Se adequa

te animals, on the other hand, had two nucletoide chagnes of which one led to an amino acid chagne.

The relationship between selenium and AIDS is well documented with progressive depletion of Se in AIDS related complex (ARC) and AIDS patietns, depletion of thyroid T3, impairment of glutatione function and low whole blood and plasma GSH-Px activity. Selenium is a critical part of the antioxidant enzyme glutathione peroxidase. In a study of  infected drug using men and women in Miami, low plasma levels of selenium were association with a 10 fold higher risk of death and a 3 fold increase of risk for development of mycobacterial disease. Several small intervention studies also provide evidence of the beneficial effects of selenium supplementation. For example, in one randomized trial in Florida (n=186), selenium (200 ug/d) resulted in significant decrease in total hospital admission rates (P=0.002) and in the percentage of hospitalizations due to infections (P=.001). However, fewer placebo treated participants were using antiretroviral drugs at baseline. In another study among 949 HIV-1 infected Tanzanian women who were pregnant, 306 of 949 women died over a 5.7 year median follow up time. Lower plasma selenium levels were significantly associated with an increased in mortality (P=.01). Plasma selenium levels were not associated with time to progression to CD4 count <200 cells/mm3 but were weakly and positively related to CD4 cell count in the first years of follow up. Thus while there is a body of oberservational evidence and several small trials which implicate selenium deficiency as an independent predictor for the accelerated progression of HIV disease, more data is needed from randomized controlled trials.

The high tunover rate in T cells in HIV infected subjects could significantly contribute to the observed decline in plasma Se levels. The mRNA of several T cell assocaited genes (CD4, CD8, HLA-DRP33) may encode selenoproteins. If this is true, bhte billions of CD4+ T cells lost daily in AIDS pateints may contribute to the progressive Se depletion.

In AIDS patients, selenium deficiency may be associated with myopaty, cardiomyopathy and immune dysfunction including oral candidiasis, imparied phagocytic function and decreased CD4 T cells.

Effect of Selenium supplementation:

Supplementation with selenium, even in selenium-replete individuals has reported immunostimulant effects. This includes an enhancement of activated T cell proliferation. For example, lymphocytes from volulnteers supplemented with Se at 200 ug per day showed an enhanced response to antigen stimulation and an increased ability tod evelop into cytotoxic lymphocytes. NK cell activity was also reportedly increased. The mechanism appears to be related to upregulation of receptors for the growth regulatory cytokine IL-2 on the surface of activated lymphocytes and NK cells.

Se supplementation inhibits both the activation of HIV1 by oxidative stress, and the activaiton of NF-kB, an important cellular transactivator of HIV-1.

What they are and Where they are found

Red wines contain a large array of polyphenolic constituents that have been shown to block carcinogenesis and to inhibit the growth of tumors in whole animals, or in cell culture by altering the activity of certain enzymes or the epxression of specific genes.

Research in the Massachusetts Institute of Technology laboratory of Leonard Guarente has shown that increasing the activity of a single gene, called SIR2, can extend the life span of yeast and that without the gene, calorie restriction does not prolong life. The Sir2 enzyme belongs to a large family of evolutionarily conserved molecules termed sirtuins. In lower organisms, such as yeast and worms, these enzymes regulate a wide range of cellular activities that affect lifespan, including modulating how tightly DNA is packaged inside cells. In mammalian cells, sirtuins act as regulators of programmed cell death and differentiation. 

Certain molecules also activate SIR2 in yeast, as well an an analogous gene, SIRT1, in human cells. These compounds include the following:

• quercetin a polyphenol found in apples and tea
• piceatannol a polyphenol
• resveratrol is a phytoalexin, one of a group of compounds that are produced in plants during times of environmental stress or pathogenic attack. Resveratol has been found in at least 72 plant species, a number of which are components of the human diet, including  mulberries, peanuts, and grapes. Resveratrol found in grapes and red wine has been shown to increase SIRT1 activity 13-fold (24 August, Nature). Many studies report that resveratrol exerts its anti-cancer effects by causing cell cycle arrest and inducing apoptosis in many different human cancers. In non-Hodgkin’s lymphoma and multiple myeloma, resveratrol not only induced apoptosis but also potentiated the effects of paclitaxel-induced apoptosis. Resveratrol was also shown to sensitize tumor cells, but not normal human fibroblasts, to TRAIL-induced apoptosis. In 2003, David sinclar of Harvard medical School in Boston and his colleagues reported that yeast dosed with resveratrol lived 60% longer than yeast that did not receive the compound. 

 are a type of polyphenol found in natural substances like .

Capsaicin: is a major phenolic compound from chili peper. It has been shown to induce cell apoptosis in vitro.

Curcumin (1.7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) is a phenolic natural product isolated from the rhizome of Curcuma longa (turmeric). Curcumin, the active component of tumeric, has been shwon to exhibit anti-inflammatory and antimutagenic and anticarcinogenic activity. Studies report that curcumin stronlgy inhibits the initiation and promotion of chemical carcinogen-induced tumor formation in mice and the proliferation of various cultured tumor cells. Thes activities may be attributed to the inhibition of certain signal transduction pathways critical to tumor cell growth, such as AP0-1, NF-kB and protein kinase c.

Hypericin from St. John’s Wort is best known in the treatment of depression. It is also known to induce apoptosis in different enoplastic cell lines. There are also some reports of anti-inflammatory potential  such as inhibition of phorbol ester-induced NF-kB activation.

Giner has been used in China for over 2500 years for colds, nasea and headaches. Ginger and its constituents have been shown to inhibit tumor promotion in mouse skin.

Gingko biloba is known to be enriched with falvonoids and has demonstrated benefits for Alzheimer’s disease. These findings are supported by in vitro studies, where the catechin EGCG or the Ginkgo biloba extract were shown to prevent amylooid B peptide (Ab)-induced neurotoxicity in cultured hippocampal neurons.

Milk contains beneficial components. Butterfar, casein and lactose are the most common. Other components include lactoferrin, lactoperoxidase, immunoglobulins, sialyllactose, phospholipids. The two major categories of milk proteins is casein and whey protein.

Cheese manufacturing; (separation of Casein from Whey): involves separation of casein, an insoluble protein contained in whole milk, from other components by precipitation. When milk is acidified (becomes sour) the casein is altered such that “curd” is formed. Curd is then used to make cheese. The liquid portion of the soured milk is the “whey” which is a by-product of the cheesemaking process, although whey made by acid coagulation and high heat (e.g., during the making of cheddar, Swiss or provolone cheeses) may be used to make recotta cheese 9A.M. Pearl et al. Completely Cheese: The Cheeselover’s Companion, Jonathan David Publishers, Inc., Middle Village, N.Y. 1978) Other cheeses made principally from whey include such Scandinavian cheeses as Gjetost, made from goat’s milk whey, and Mysost, made form cow’s milk whey, as well as Sapsago, a cheese made in Switzerland from cow’s milk whey.

Infant formulas of Milk: Bovine milk and human milk have a number of differences in the protein composition. For example, bovin milk contains beta-lactoglobulin which is not in human milk. Some infants show different degrees of intolerance to bovine milkd and compositions of non-allergenic milk products which lacks the beta-lactoglobulin exist. 

Iron is an essential trace element required for growth and development of all lving organisms. 

Regulation of Iron (homeostasis)

Iron content is reuglated by controlling iron absorption, Iron recycling and release of iron from the cells in which it is stored.

Hepcidin: is an important regulator of iron homeostasis. High levels of human hepcidin result in reduced iron levels and vice vera. Mutations in the hepcidin gene which result in lack of hepcidin activity are associated with juvenile hemochromatosis, a severe iron overload disease. (Foltz, US12/990137)

Increasing evidence suggests that hepcidin is involved in iron sequestration during inflammation. Hepcidin gene expression has been observed to be robustly upregulated after inflammatory stimuli, such as infections. A strong correlation between hepcidin expression and anemia of inflammation was also found in patients with chronic inflammatory diseases, including bacterial, fungal and viral infections. (Foltz, US12/990137).

Human hepcidin is a 25 amino acid peptide. Its cDNA encodes a 83 amino acid pre-propeptide in mice and an 84 amino acid pre-propeptide in rat and human. The 24 residue N terminal signal peptide is first cleaved to produce pro-hepcidin, which is then further processed to produce mature hepcidin. (Foltz, US12/990137)

Ferritin is an iron storage protein that plays a key role in iron homeostasis and cellular antioxidant activity. The amino acid sequences of ferritins isolated from different species are very different; mammalian ferritins are mainly composed of structurally similar heavy (H)-chain (21 kDa) and light (L)-chain (19 kDa) subunits. (Du, “Potential of Ferritin-Based Platforms for Tumor Immunotherapy” Molecules, 27(9), 2022). 

Iron Absorption: Iron is absorbed predominantly in the duodenum and upper jejunum by enterocytes. A feeback mechaism exists that enhances iron absorption in individuals who are iron deficient and that reduces iron absorption in people with iron overload. (Andrews, Ann. Rev. Genomics Hum. Genet., 1: 75 (2000).

Iron Recylcing: 

Iron is recycled from degraded red cells by reticuloendothelial macrophages in bone marrow, hepatic Kupffer cells and spleen. 

Iron Release: 

–Ferroportin: Iron release is controlled by ferroportin, a major iron export protein located on the cell surface of enterocyctes, macrophages and hepatocytes, the main cells capable of releasing iron into plasma. Hepcidin binds to ferroportin and decreases its functional activity by causing it to be internalized form the cell surface and degraded. (Foltz, US12/990137)

Disorders of Iron Hoemeostasis

Common disorders of iron homeostasis include anemia, spesis, anemia of inflammation, anemia of cancer, chemotherpay induced anemia, chronic inflammatory anemia, congestive heart failure, end stage renal disorder, chronic kidney disease, iron deficiency anemia, ferroportin disease, diabetes, rheumatodi arthritis, arteriosclerosis, tumors, and red blood cell disorders. 

Treatment of Anemia/iron disorders

(Foltz, US12/990137) teaches methods of treating a human with elevated levels of hepcidin by adminstiering anti-hepcidin antibodies either alone or in combination with an erythropoiesis stimular such as erythropoietin. (see therapeutic applications of antibodies). 

Antioxidants are a highly effective group of protective agents that act to regulate oxidative reactions. Essential antioxidants are either endogenous (internally synthesized) or exogenous (consumed). They are often categorized as scavenger antioxidants and prevention antioxidants.

Scavenger antioxidants remove ROS and include small molecule antioxidants such as water soluble compounds like Vitamin C or glutathione and lipid soluble compounds such as vitamin E, carotenes, lipoic acid and Coenzyme Q. They also include large molecule enzyme antioxidants such as superoxide dismutase (SOD) that detoxifies the superoxide ion, catalase, which deals with hydrogen peroxide and glutatione peroxidase (GPx) which detoxifies cellular peroxides. These enzymes must be synthesized by cells and are subject to genetic and/or macromolecular regulatory mechanisms.

SOD first reduces (adds an electron) to the radical superoxide (O2-) to form hydrogen peroxide (H2O2) and Oxygen (O2). 2O2- + 2H —SOD >>>>>H2O2 + O2

Catalase and GPx then work with the protein glutathione to reduce hydrogen peroxide and produce water.

2H2O2 —CAT >>>>>H2O2 + O2

H2O2 + 2glutathione –GPx >>>>>oxidized glutathione + 2H2O

Preventative antioxidants hinder the formation of new ROS. These are proteins that bind ROS to protect essential proteins and include albumin, metallothionine, transferrin, cerulplasmin, and myoglobin.

It is important to note that many of these vitamins do not act in isolation from other antioxidants; rather, they are part of an interlinking set of redox aminoxidant cycles, termed the “antioxidant network.” For example, Vitamin E is efficiently reduced from its free radical form (tocotrienoxyl to tocopheroxyl) that arises after quenching lipid radicals to retun back to its native state (tocotrienol and tocopherol) by vitamin C. Vitamin C can regenerate vitamin E directly, while thiol antioxidants, such as glutatione and lipoic acid, can also regenerate vitamin E indirectly via vitamin C.

Oxidative stress is worsened in infection if micronutrients are deficient.

Markers for oxidative stress include 8-hydroxy-2′-deoxyguanosine.

Carotenoids are a class of yellow, orange and red plant derived compounds. All of the more than 600 known carotenoids are antioxidancts and about 50 are vitamins because they have provitamin A activity. Vitamin A refers to preformed retinol and the carotenoids that are coverted to retinol by cleavage of a central bond.

Flavonoids: are naturally occuring plant polyphenols found in abundance in diets rich in fruits, vegetables, and plant-derived beverages such as tea. They are well known to have antioxidant effects. Plant polyphenols have phenol rings that act as electron traps to scavenge peroxy radicals, superoxide anions, and hydroxyl radicals.

The antioxidant effects of tea polyphenols are considered to be associated with their ability to stimulate antioxidant defense metabolism through the redox-regulated transcription factors and mitogen-activated protein kinases (MAPK)-dependent cell cycle regulation.

–Blueberries: are very high in antioxidants.

–cranberry falvonoid contain anthocyanins and favonols, and have been found useful in the immune response to oxidize low-density lipoprotein (LDL) and its uptake by endothelial macropahges.

-Chili peppers are a food item found with many essential nutrients such as vitamin C, provitimains A and E and several B vitamins.

—Mushrooms: a high in antioxidants.

—Pure Cocoa: contains an abundance of polyphenols. However, there is also a lot of sufar and saturated fat found in chocalet bars.

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Vitamin E was discovered as a mcironutrient that is indispensable for reproduction in female rates. In humans, vitamin E deficiency can result in various neurological lesions.

Vitamin E is a fat soluble, like vitaimin A, and composed of a family of 8 related compounds, the tocopherols and tocotrienols. Vitamin E is a strong antioxidant that can support monocyte/macrophage mediated responses. Vitamin E can scavenge free radicals. It is considered one of the most potent fat soluble antioxidants due to its ability to donate electrons, hence interfering with the damaging effects of the oxidation process. It is needed in immune function and supplementation enhances cell mediated immunity in elderly patients. Research shown it plays an important role in the differentiation of immature T cells in the thymus, inducing higher differentiation that results in improved cellular immunity.

Vitmain E influances T cell function by downmodulating prostaglandin E2 in elderly subjects.

Viramin E can decrease serum levels of TNF-alpha and protein kinase C. TNF-alpha incdreases the activity of phospholipase A2. In monocytes, phospholipase A2 stimulates the replicaiton of HIV.

When supplementing with vitamin E, one should always consider selenium since these two nturients act synergistically.

The current RDI is 20 mg. Major dietary sources include salid oils, margarine, legumes and nuts. The immunostimulating effect of vitamin E can usually be acheived by administering 200-800 mg of vitamin E daily. Vitamin E reduces hydrogen peroxide which is used especially by neutrophils to kill microorganisms. So that excessively high use could reduce bactericidal and proliferative activity of periopheral leukocytes.

Links: Vitamin university  MedlinePlus  axcella  (amino acids as food)

Drug Interactions

Companies engaged in Nutritional Research:  Asha Nutricion Sciences 

Nutritional deficiencies can lead to increased susceptibility to infectious diseases. Many viral infections such as rotavirus, measles and parinfluenza virus, for example, are much more severe in malnourished hosts as compared with well noruished hosts. Vitamin A, beta-caroteine, folic acid, vitamin B12, vitamin C, riboflavin, iron, zinc and selenium have immunomodulating functions and influence both the susceptibility of the host to infectious diseases and the course and outcome of these diseases. 

Not only may the immune response be impaired in nutritionally deficient hosts, but the viral pathogen itself may be affected by nutritional deficiency. Several viruses have been shown to develop increased virulence due to changes in their genomes as a result of replicating in a nutritionally deficient host. The mechanism for this is not well understood but appears to be related to increased oxidative stress in the deficient host. Thus the host as well as the pathogen itself can be influenced by the nutritional status of the host.

When supplementing your diet with vitamins be alert to possible drug nutrient interactions. Such interactions can occur directly between the drug and vitamin, typically during digestion and absorption. The binding of metals by tetracycline is an example of such direct interaction. In the alternative, functional interactions can occur in the gastrointestinal tract which alter GI function and affect digestion and absorption of both the drug and the nutrients. An example is grapefruit jice which increases the amount of drug that enters the bloodstream because it inhibits the an enzyme of interstinal cytochrome P450. This enzyme CYP3A4 is in the cells that line the samll intestine and helps to break down about 1/2 of all marketed drugs.

Vitamin A refers to a family of fat soluble compounds called retinoids, which have vitamin A activity. About 50 of the more than 600 carotenoids can be converted to vitamin A. It is essential in vision, particularly night vision. The current RDI is 1500 ug/L. Natural sources of vitamin A are solely animal sources and include organ meats, fish, egg yolks and fortified milk. Vitamin A deficiency imparis mucosal barriers and diminishes the function of neutrophils, macrophages and NK cells.

Amino Acids

Amino acids are important in disease. Axcella has a database of food and food proteins which may help in disease. 

Vitamin A supplementation is recommended as a tratment for severe measles infection and also as a supplementation at the time of vaccination for measles infection. Viramin A deficiency is associated with the development of severe measles infections, leading to a high rate of mortality.

Orange fruits and vegetables such as carrots and sweet potatoes are rich in beta carotene which is converted to vitamin A. 

Vitamin C  see outline

Vitamin D see outline

Vitamin E: is an antioxidant. Trolox, Hoffman-LaRoche’s trade name for 6-hydroxy-2,5,7,8-tetramethylchorman-2-carboxylic acid, is a water soluble derivative of vitamin E and used in biological or biochemical applications to reduce oxidative stress or damage. Trolox equivalent antioxidant capacity (TEAC) is a mesurement of antioxidant strength based on Trolox. Due to the difficulties in measuring individual antioxidant components of a complex mixture such as green tea, Trolox equivalency is used as a benchmark for the antioxidant capacity of such a mixture.

Sunflower seeds are good sources for Vitamin E.

Sacha inchi (Plukenetia volubilis) is a plant native to Peru which is rich in vitamin E.  The term “sacha inchi” typically refers to edible seeds produced by the sacha inchi plant. Also known as sacha peanut, mountain peanut, or Inca peanut, these seeds have a nut-like flavor when roasted.

Vitamin K is fat solube and essential for normal clotting, specifically for production of prothrombin factors VII, IX and X and proteins C and S. The RDI is 80 ug/L. Dietary sources include dark green vegetable, aprticularly spinach, but it is also synthesized by intestinal bacterial.

Folate, vitamins B6, B12 effect homocysteine. Elevated plasma total homocysteine level is a mjaor risk factor for coronary disease. Folate is a water solube B vitamin that is necessary in forming coenzymes fo rpurine and pyrimidine synthesis, erythropoiesis and methionine regeneration. The current RDI is 400 ug. The richester food sources are darkened green leafy vegetables, whole gran cereals, fortified grain products and animal products. Since 1996 in the US all flour and uncooked cereal grains have been supplemented with 140 ug of folate per 100 g of flour. Interest has grown in the effects of folate supplementaiton in cancer prevention since higher intake appears to reduce the risk of colon and breast cancer, particularly among moderate consumers of alcohol.

Iron: is an essential element that is required for numerous cellular functions. In mammals, the supply of iron to the body is regulated to match the body’s iron requirements at the level of iron absorption by duodenal enterocytes.

Calcium: is a mineral that is critical to bone strenght. But calcium does not work by itself. Healthy bones require a mix of calcium, phosphorus and magnesium. They also need adequate protein to form their basic framework, vitamin K to maintain structural proteins, vitamin D for calcium absorption and exercise to stimulate bone building cells. Recommended intake is 10,000 milligrams a day for adults–1,200 for wormen older than 50 and 1,300 for teens.

OMEGA-3 fatty acids: may beneift not just the heart but apsychiatric and neurological problems. This includes bipolar disorder, schizophrenia, depression, ADHD, Alzheimer’s. The brain is 60% and need omega-3s for optimal function. Studies suggest they help build cell membranes, boose levels of serotonin and incease the number of connections between neurons.

The short-chian omega-3s can be found in walnuts, flaxseed, canola oil and lefy green. The long-chain versions (which may be most beneficial for the brain) can be found in seafood and omega-3-enriched eggs. The American Heart Association also recommends eating fatty fish at least twice a week for the prevention of heart disease.

–Krill Oil:

Krill oil is a good source of omega-3 fatty acids. SuperBaKrill

Chromium: is a mineral that is involved in sugar metabolisms. Whenever your body mobilizes stored glucose, it requires chromium to do that. Research shows that it may help diabetic and pre-diabetic patients boost their insulin sensitivity by increasing both the number of insulin receptors on cells and activity of those receptors.

Chromium can be found in broccoli, apples. The current recommendation is 25 to 35 micrograms a day.

Zinc and essential nutrients

Zine is regarded as one of the most important nutrients required for immune health–it is involved in over 60 enzyme systems in the body, many of which are part of the immune system. Zinc intervenes in immune processes mainly through its influence on the maturation of lymphocytes, production of cytokines, generation of free radicals, regulation of apoptosis and gene transcription. Zn deficiency brings about a decrease in the ability of macrophages to kill intracellular parasites, a decreased production of various cytokines (IL-2, IL-12, IFNy, TNF) and antigen-mature cells (CD4+, CD45RO+), reduced levels of Th lymphocytes and a decreased NK activity. Essential nutrients (methionine, cystein, arginine, vitamins A, B, C, E, selenium and Zinc) deficiency can lead to a premature transition from efficient Th1 dependent cellular antiviral immune functions to Th2 dependent humoral immune functions which has implications for many diseases such as cancers and AIDS. For example, under Th2, levels of IL-4, IL-6, Il-10, leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) are raised, while levels of Il-2, Zn++, NO and other substances are lowered. This makes it easier for viruses like which multiple more efficiently in Th2 cells. The cell surface receptor for LTB4 also seems to be a co-receptor for CD4, which helps  to infect under Th2. In respect to Zinc, however, higher levels of zinc intake were actually associated with faster disease progression, so the verdict may not be in on the effectiveness of zinc with respect to HIV.

Zn shortage brings about an increase in the level of the plasma corticosterone which contributes to T cell immunosupression. The presence of minerals including zinc and copper is also important to production of superoxide dismutase (SOD), an endogenous enzyme that provides various antioxidant protections to cells.

Zinc deficiency promotes cancer. Under the influence of Th1 cells, zinc inhibits the growth of tumors by activating the endogenous tumor suppressor endostatin, which inhibits angiogenesis.

The recommended daily Zn dose is 15 mg. In old individuals, Zn supllementation can have preventive or even therapeutic effects against influenza and possibly other infections. However, such supplementation should not exceed the recommended daily allowance and show not last more than 1-2 months.

In patients withe the fourth clincial stage of AIDS, a daily Zn suplment of 45 mg over a period of 1 month together with a Zidovudine therapy induced a total elimination of opportunistic infections by Candida aesophageo and Pneumocystis carinii in comparison to patients with the same stage of AIDS treated only with Zidovudine.

Foods rich in Zinc: Oysters contain an abundance of zinc.

FDA weight loss drugs

Stimulants:

Amphetamines:

Amphetamines such as Adderall, Adderall XR, Dextroamphetamine and Mydasis are stimulates which can help people with ADHD. Some people use amphetamines for weight loss or to boost energy and alertness. High doeses can cause a rise in body temperature, irregular heartbeat and even cardiac arrest. Nicknames for amphetamines include “speed”, “black beauties” or “bennies”. 

Methyphenidate: is a stimulate in ADHD drugs such as Concerta, Daytrana, Metadate, Methylin and Rtalin. 

FDA Approved Medicines for weight loss

Contrave: (AKA/ naltrexone/Bupropion): Nalpropion Pharmaceuticals, Inc. holds New Drug application No. 200063 for and markets Contrave for weight management in overweight or abese adults. Nalpropion also holds three patents: US Patents No: 7,462,626 drawn to a method for treating overweight or obesity by adminsitering bupropion in an amount effective to induce weight and adminsitering naltrexone in an amount effective to enhance the weight lowss activity of buropion. However, these patents were held to be invalid for obviousness given the prior art literature below. The court holding that the combination of the drugs could not have been unexpected given that the combination of the two drugs was already known and that both drugs were understood to be useful for the purpose of inducing weight loss. 

O’Malley (US Patent No: 6,541,478) entitled “Smoking Cessation Treatment Using Naltrexone and Related Compounds” discloses that weight gain is a significant problem with smoking cessation and that the use of opinoid antagnonist, including naltrexone, alone or with other withdrawal attenuating agents minimizes weight gain during treatment. 

Jain “Bupropion SR vs. Pacebo for weigth loss in obese patients with depressive symptoms” 10 Obesity Res. 1049-56 (2002), J.A. 7171-78) discloses that studies suggest that bupropion SR is also effective for weight loss)

Atkinson (“Bupropian SR Enhances Weight Loss: A 48-week double-blind, placebo-controlled trial, 10 Obesity Res. 633-41 (2002), J.A. 7160-68) discloses a small but significant weight loss in women but no significant effect in mean with long-term naltrexone administration. 

Dante (US Patent no: 5,817,665) discloses that a woman in her thirites who was started on naltrexone without making any other changes rapidly lost her craving for sweets and lost thrity pounds in three weeks. 

Using Bacteria to Control Weight Loss

Arla Foods amda, the largest producer of dairy produces in Scandanavia, has patnet 9,113,641 which relates to a composition of L. paracasei and a milk product used to regulate fat uptake. 

Jiinis Biopharmaceuticals has a patent directed to mutagenized L. acidophilus strains. 

Nestec S.A. has a number of patents relacting to formulations of lactic acid bcteria used to prevent weight gain. Patent Nos. 8,318,150, 8318,151 describe the use of two strains of the same probiotic species, Lactobacillus rhamnosus whereas Patent No. 8,440, 178 describes the use of two additional L. rhamnosus strains and Patent No. 8,454,949 related to the use of similar probiotic species, L. helveticus. Another patent 9,101,651 is for the use of probiotic L. rhamosus strain.  

Foods for Weight Loss: 

The benefits of a diet rich in fruits, vegetables, legumes, nuts and whole grains is hard to dispute. Combined with exercise, an ideal body weight and a bit of alcohol, that kind of diet is your best bet against chronic ill health.

Other ways to deliver Nutraceuticals

Chewing Gum:

Fertin Pharma has weight loss products in the form of chewing gum. 

Micro-Laser

Sono-Bello