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Plasma transport proteins such as transferrin discount sarafem 10 mg online menstrual epilepsy, retinol-binding protein discount sarafem online visa women's health clinic topeka ks, and thyroid-binding prealbumin have a shorter half-life and smaller pool size than albumin and are consequently better indicators of current protein status buy sarafem overnight 4 menstrual cycle stages. Because they are negative acute- phase reactants, their levels tend to be lowered by infection. Retinol-binding protein tends not to respond to depletion if there is vita- min A or zinc deficiency, and transferrin is affected by iron status. Pregnancy, exercise, and insulin level may also affect plasma transport 156 Part One / Principles of Nutritional Medicine protein levels. Urinary 3-methylhistidine and urinary creatinine values are not very use- ful markers but insulin-like growth factor I may prove to be a sensitive indi- cator of protein status. The meaningful interpretation of amino acid profiles, either plasma or urinary, is exceedingly complex, and practitioners need to form liaisons with laboratories that specialize in such analyses. Information relevant to a num- ber of areas can be obtained by such investigation. Blood lev- els, on the other hand, obviate the compounding effects of kidney function (normal and abnormal) and may be a better measure of the nutritional sta- tus of individual amino acids, especially those like methionine and trypto- phan, which may be barely present in urine. This implies that in the population as a whole, there is a set of amino acid phenotypes that have different requirements for amino acid intake, including “semi-essential” amino acids. The emphasis of this research on assessing metabolic profiles as opposed to seeing amino acids as individual entities is important and highlights the necessity for systemic thinking in the area of organismic homeostasis. Alanine, glycine, glutamine/glutamic acid, and serine are the principal metabolites used by the clustering technique to divide the groups. Tyrosine, 3-methylhistidine, and 1-methylhistidine were excluded from the profiles because they are catabolic markers often increased in exercise, psychologic stress, trauma, or infection. Organic Acid Analysis Like amino acid analysis, organics profiling is a nascent science in which rig- orous research has not yet caught up with clinical use and commercial hype. However, with the inclusion of neutral compounds of fungal origin, we are better advised to use the term organics profiling. In the recent history of clinical biochemistry, a significant impetus to the study of organic acids came through attempts to elucidate inborn errors of metabolisms. Lonsdale21 has given us a fascinating and highly readable account of the evolution of his clinical philosophy from his early days as a researcher and pediatrician working with inborn errors to his later experi- ence as a fully fledged practitioner of nutritional medicine. In common with other nutritional pioneers, he realized that nutritionally responsive, inher- ited disorders were but one end of a spectrum of biochemical competence and that many individuals had conditions that could be viewed as attenu- ated versions of the fully blown classical picture. His earlier account of thi- amine dependency and the role of energy metabolism in the protean manifestations of dysautonomia is a modern medical classic. Assay of citric acid cycle intermediates may provide insight into metabolic deficits that are potentially correctable by supplying nutrient cofactors. Thus high citrate and cis-aconitate levels with low or lownormal isocitrate levels could imply an inefficiency in the enzyme aconi- tase, which affects the two-step conversion from citrate to isocitrate. This defect might be ameliorated by cysteine (as a glutathione enhancer), iron, or both. This means that a low level of α-ketoglutarate, for example, can potentially be corrected by added glutamine. Fatty acid transport into mitochondria for oxidation may be impaired as a result of carnitine deficiency. This results in an alternative oxidation path- way, which leads to the production of adipic and suberic acids. Methylmalonic acid is probably the best known exam- ple of an organic acid marker of vitamin deficiency. In this case, a lack of vitamin B12 compromises the activity of methylmalonyl-CoA mutase, which converts methylmalonyl coenzyme A to succinyl coenzyme A.

An accepted regime for treating vitamin B12 deficiency is to initially administer 1000 μg of vitamin B intramuscularly each week cheap sarafem uk menstrual seizures. Patients with overt atrophic gastritis require regular injections to avoid vitamin B12 deficiency purchase sarafem without prescription menstruation 6 weeks postpartum. Strict vegetarians who fail to take vitamin B12 supplements are similarly at risk of neurologic disorders buy sarafem 20mg online menopause foggy brain. An infor- mal study found that a substantial proportion of patients with normal serum B12 concentrations did indeed feel better following injections of hydroxy- cobalamin, but not following injections of sterile water. Although a longitudinal, multicenter study of an elderly population found no significant correlations between mental health and vitamin B or folate,8 12 there is a persistent belief that vitamin B12 may affect mental alertness. A study of vegans did suggest that cobalamin deficiency, in the absence of hematologic signs, may lead to impaired cognitive performance in adoles- cents. However, a dou- ble-blind study found 3 mg methylcobalamin administered over 4 weeks was not an effective treatment for sleep-wake rhythm disorders. A randomized, prospec- tive clinical trial concluded that a vitamin B12 cream containing avocado oil had considerable potential as a well-tolerated, long-term, topical therapy of psoriasis. Further investigation into a role for vitamin B12 in treatment of multiple sclerosis and prevention of ischemic heart disease also deserves con- sideration. Of more concern is that high doses of folic acid may mask a vitamin B12 deficiency. Absorption of vitamin B12 may be impaired by drugs that reduce hydrochloric acid secretion (e. Alcohol, antibiotics, colchicine, methyldopa, and metformin are among the drugs that reduce absorption of this vitamin. Treatment of pernicious anemia with folic acid improves the blood picture but neural damage progresses. Selhub J: Folate, vitamin B12 and vitamin B6 and one carbon metabolism, J Nutr Health Aging 6(1):39-42, 2002. Brighthope I: Nutritional medicine tables, J Aust Coll Nutr Env Med 17:20-5, 1998. Wynn M, Wynn A: The danger of B12 deficiency in the elderly, Nutr Health 12(4):215-26, 1998. SoRelle R: Fortification of food with vitamin B12 in addition to folic acid might reduce cardiovascular disease risk, Circulation 105(4):E9070, 2002. Eussen S, Ferry M, Hininger I, et al: Five year changes in mental health and associations with vitamin B12/folate status of elderly Europeans, J Nutr Health Aging 6(1):43-50, 2002. Ito T, Yamadera H, Ito R, et al: Effects of vitamin B12 and bright light on cognitive and sleep-wake rhythm in Alzheimer-type dementia, Psychiatry Clin Neurosci 55(3):281-2, 2001. Mayer G, Kroger M, Meier-Ewert K: Effects of vitamin B12 on performance and circadian rhythm in normal subjects, Neuropsychopharmacology 15(5):456-64, 1996. Okawa M, Takahashi K, Egashira K, et al: Vitamin B12 treatment for delayed sleep phase syndrome: a multi-center double-blind study, Psychiatry Clin Neurosci 51(5):275-9, 1997. Takahashi K, Okawa M, Matsumoto M, et al: Double-blind test on the efficacy of methylcobalamin on sleep-wake rhythm disorders, Psychiatry Clin Neurosci 53(2):211-3, 1999. Stucker M, Memmel U, Hoffmann M, et al: Vitamin B12 cream containing avocado oil in the therapy of plaque psoriasis, Dermatology 203(2):141-7, 2001. The cost and safety profile of vitamin C favors its empiric use in recom- mended doses.

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A number of organic acids may arise from the metabolic activities of gut microflora order sarafem line women's health clinic utah. Shaw24 has drawn attention to abnormal products from yeast or fungal overgrowth order sarafem 10mg without a prescription omega 7 menopause, which may interfere with glucose metabolism buy sarafem 20mg overnight delivery women's health center york pa, citric acid cycle activity, protein synthesis, and cofactor binding. These substances include arabinose, tartaric acid, citric acid, and citramalic acid. Hippuric acid levels may be elevated with toluene exposure (but can be abnormal as a result of gut dysbiosis), and orotic acid is a sensitive measure of poor ammonia disposal. Organic profiles usually contain far more compounds than have been listed here, but the clinical utility of many of these measurements has yet to be established. We should be cautioned by the years of research expended on neurotransmitter metabolites such as 5-hydroxyindoleacetic acid (from serotonin). Originally mooted as a possible marker of brain 5-hydroxytryptamine activity, the test came under increasing scrutiny with the discovery that cerebral spinal fluid 5-hydroxyindoleacetic acid seemed largely to be a product of the spinal cord and to reflect general activity level rather than brain serotonin release. How much less valid then is the idea that urinary 5-hydroxyindoleacetic acid may reflect something about the central nervous system and mood? Vitamins and Minerals The body, with its hierarchy of systems, is like a community of citizens. Events such as famine or epidemic disease that have adverse consequences for the community as a whole will have different effects on individual mem- bers; some will be affected greatly and some, minimally. The part can never reliably reflect the whole, and so it is with biochemical testing. A number of tests are potentially available for each nutrient, and we are concentrating on those that are endorsed by scientific consensus as repre- senting best current practice. However, these do not necessarily reflect the current pattern of use among a majority of clinicians or the profile of tests offered by laboratories. Chapter 6 / Assessment of Nutritional Status 159 It is also important to remember that the sum value of two poor or mediocre tests does not provide a result of superior inferential validity (e. Direct assessment of vitamin A stores by means of liver biopsy is the most accurate, although usually undesirable, method. Plasma meas- urements are not helpful because levels tend to be maintained until liver reserves are exhausted. Conjunctival impression cytology is a rapid, cheap, and non-invasive way of screening populations at risk (e. It evaluates the development of squamous metaplasia and loss of goblet cells from the conjunctiva but may be con- founded by eye infections or other sources of irritation. The relative dose- response test has also been successfully used in human population studies. It depends on the release of holo–retinol-binding protein by the liver after the administration of a large dose of retinyl acetate; the difference between baseline and 5-hour levels of serum retinol gives an index that is elevated in deficiency states. Thiamine level is best estimated by the erythrocyte transketo- lase stimulation test with stimulation in vitro by addition of thiamine pyrophosphate. Confounding variables include long-term alcohol consump- tion, diabetes, pernicious anemia, negative nitrogen balance, and infection. Riboflavin level is usually measured by erythrocyte glu- tathione reductase activity with stimulation by flavin adenine dinucleotide.