Research on Salicylate Sensitivity

For every article referenced I tried my very best to track down the open-sourced full text pdf to post. If only an abstract is linked, I am unable to post the full text article for you for copyright reasons. However, I likely have it in my personal collection. Please feel free to contact me (form at bottom) if you have a question about an article. I will be doing my best to talk about research articles on YouTube, especially when the full-text is unavailable for the public. Many scientists don't mind if you contact them directly (find their lab, clinic, or university) and ask them for the full article. They often have the ability to send it to you. I am adding to this list weekly. Oh, and by the way, I don't think one should have to pay for information, but that's another conversation for another day.


Getting started

These resources below were probably some of the most important when I first got started.


Tested Foods - Research Studies Testing Levels of Salicylates

  • Malakar S, Gibson P R, Barrett J, Muir J G. Naturally occurring dietary salicylates: A closer look at common Australian foods. Journal of Food Composition and Analysis. 2017; 57:31-39. View full pdf at:
  • Swain AR, Dutton SP, Truswell AS. Salicylates in foods. J Am Diet Assoc. 1985;85(8):950–960. View full pdf at:
  • Kęszycka PK, Szkop M, Gajewska D. Overall Content of Salicylic Acid and Salicylates in Food Available on the European Market. J Agric Food Chem. 2017;65(50):11085-11091. doi:10.1021/acs.jafc.7b04313
  • Wood A, Baxter G, Thies F, Kyle J, Duthie G. 2011. A systematic review of salicylates in foods: estimated daily intake of a Scottish population. Mol Nutr Food Res. 55 Suppl 1(S1):S7–S14. doi:10.1002/mnfr.201000408. View abstract:
    Identified that salicylates are found in alcoholic drinks, herbs and spices, fruit, juices, tomato based sauces and vegetables. Provides the levels of salicylic acid found in each food tested.
  • Scotter MJ, Roberts DP., Wilson LA, Howard FA., Davis J, Mansell N. Free salicylic acid and acetyl salicylic acid content of foods using gas chromatography–mass spectrometry. Food Chemistry. 2007;105(1):273-279. doi:10.1016/j.foodchem.2007.03.007
  • Venema, D P, Hollman, P C, Janssen, K P, Katan, M B. Determination of acetylsalicylic acid and salicylic acid in foods, using HPLC with fluorescence detection. Journal of Agricultural and Food Chemistry. 1996; 44(7):1782–1787. Read abstract at:
  • Robertson, G and Kermode, W. Salicylic acid in fresh and canned fruit and vegetables. Journal of Science and Food and Agriculture. 1981; 32: 833-836. doi:10.1002/jsfa.2740320813.
  • Edyta Protasiuk, Małgorzata Olejnik. Residues of salicylic acid and its metabolites in hen plasma, tissues and eggs as a result of animal treatment and consumption of naturally occurring salicylates. Food Additives & Contaminants: Part A 2020, 51 , 1-9.




Research articles supporting that salicylates (including other food chemicals) may negatively impact health

General poor symptoms

  • Azuma K, Uchiyama I, Katoh T, Ogata H, Arashidani K, Kunugita N. 2015. Prevalence and characteristics of chemical intolerance: A Japanese population-based study. Arch Environ Occup Health. 70(6):341–353. doi:10.1080/19338244.2014.926855. View abstract: . Japanese study estimates that 7.5% of population is sensitive to natural food chemicals.
  • Baenkler HW. Salicylate intolerance: pathophysiology, clinical spectrum, diagnosis and treatment. Dtsch Arztebl Int. 2008;105(8):137–142. doi:10.3238/arztebl.2008.0137.
  • George, R et al. Frequency of reactions to foods containing natural salicylates in aspirin sensitive patients. Journal of Allergy and Clinical Immunology. 2000; 105(1):S135. doi: Read conference summary:
    44% of patients screened who have had hives or asthma from aspirin reaction also declare sensitivity to foods high in natural salicylates (natural aspirin compounds). Symptoms manifest as respiratory issues, urticaria (hives and skin issues), Oral Allergy Syndrome, throat swelling, flushing, and general feeling of being unwell. Many patients reacted to more than just one food. This is a conference summary/feasibility study to launch more research.
  • Maintz L, Novak N. 2007. Histamine and histamine intolerance. Am J Clin Nutr. 85(5):1185–1196. doi:10.1093/ajcn/85.5.1185. [accessed 2022 Feb 28]. Full text article:
  • Kęszycka PK, Lange E, Gajewska D. 2021. Effectiveness of personalized low salicylate diet in the management of salicylates hypersensitive patients: Interventional study. Nutrients. 13(3):991. doi:10.3390/nu13030991. [accessed 2022 Feb 28].
  • Skypala IJ, Williams M, Reeves L, Meyer R, Venter C. Sensitivity to food additives, vaso-active amines and salicylates: a review of the evidence. Clin Transl Allergy. 2015;5:34. Published 2015 Oct 13. doi:10.1186/s13601-015-0078-3 Full text at:

Asthma/Lung Issues

  • Hodge L, Yan KY, Loblay RL. Assessment of food chemical intolerance in adult asthmatic subjects. Thorax. 1996;51(8):805–809. doi:10.1136/thx.51.8.805. Full article:
    Identification of food chemical intolerance in asthmatic subjects can be reliably assessed by changes in the forced expiratory volume in one second (FEV1). Strict dietary elimination prior to testing and then measurement of FEV1 after double blind food chemical challenge remains the most reliable method for the detection of food chemical intolerance in asthmatic subjects. Chemicals test included: metabisulphite, aspirin, monosodium glutamate, artificial food colours, and sodium nitrite/ nitrate.
  • Park HS, Lim YS, Suh JE, Rhu NS, Cho DI, Kim JW. Sodium salicylate sensitivity in an asthmatic patient with aspirin sensitivity. J Korean Med Sci. 1991;6(2):113‐117. doi:10.3346/jkms.1991.6.2.113. Read article:

Digestion (unrelated to gluten-sensitivity)

  • Malakar S. Bioactive food chemicals and gastrointestinal symptoms: a focus of salicylates. J Gastroenterol Hepatol. 2017;32 Suppl 1:73-77. doi:10.1111/jgh.13702
  • Stein, Herbert L. MD (Retired) Annatto and IBS, Journal of Clinical Gastroenterology: November-December 2009 - Volume 43 - Issue 10 - p 1014-1015 doi: 10.1097/MCG.0b013e3181ae4e1b
    • Wife had IBS for 40 years and after a trip to Europe with no symptoms they figured out it was annatto in her foods.
    • Marlene Stein's video she made:
  • Tuck CJ, Malakar S, Barrett JS, Muir JG, Gibson PR. 2021. Naturally-occurring dietary salicylates in the genesis of functional gastrointestinal symptoms in patients with irritable bowel syndrome: Pilot study. JGH Open. 5(8):871–878. doi:10.1002/jgh3.12578. Read full article at:
    An elimination-rechallenge dietary approach targeting naturally-occurring bioactive chemicals has been proposed to alleviate functional gastrointestinal symptoms. A major focus of this approach is salicylates. This study aimed to address the potential role of dietary salicylates in the induction of symptoms in patients with irritable bowel syndrome (IBS). A pilot, double-blind, randomized, cross-over trial of 2-week low- versus high-salicylate diets (6.6 and 27.9 g/day salicylate, respectively) was undertaken. All foods were provided containing minimal quantities of other potential food triggers.
  • Raithel M, Baenkler HW, Naegel A, et al. Significance of salicylate intolerance in diseases of the lower gastrointestinal tract. J Physiol Pharmacol. 2005;56 Suppl 5:89-102. Full text article:

Gluten-related articles

  • Faulkner-Hogg KB, Selby WS, Loblay RH. Dietary analysis in symptomatic patients with coeliac disease on a gluten-free diet: the role of trace amounts of gluten and non-gluten food intolerances. Scand J Gastroenterol. 1999;34(8):784–789. doi:10.1080/003655299750025714. Read abstract:
    31 Celiac Disease patients with continued GI symptoms while following a strict gluten-free diet, participated in an open and double blind study by going on a strict food chemical elimination diet. 77% (24 participants) had improvement in their symptoms and they discovered that amines, salicylates, and soy provoked their symptoms. 

Skin issues including hives (urticaria)

  • Thune P, Granholt A. Provocation tests with antiphlogistica and food additives in recurrent urticaria. Dermatologica. 1975;151(6):360‐367. doi:10.1159/000251361. Abstract from:
    100 patients (53 women, 47 men) suffering from recurrent urticaria were tested with different food additives such as 8 dye additives, 7 preservatives and 7 antiphlogistica. In total did 62 patients react with urticaria and/or angio-oedema.
  • Ros AM, Juhlin L, Michaëlsson G. A follow-up study of patients with recurrent urticaria and hypersensitivity to aspirin, benzoates and azo dyes. Br J Dermatol. 1976;95(1):19‐24. doi:10.1111/j.1365-2133.1976.tb15532.x. View Abstract:
    We have studied seventy-five patients with recurrent urticaria and angio-oedema of more than 4 months duration and with positive provocation tests to aspirin, azo dyes, and/or benzoates. Cross-reactions between the test compounds were common. The patients were recommended to be on a diet free from salicylates, benzoates, and azo dyes. They were then followed for 6-24 months. At the follow-up, 24% were free from symptoms, 57% considered themselves much better and 19% stated that they were slightly better or unchanged. All patients had followed the diet for at least 1-3 months. Most of those who became totally free of symptoms did not continue with the diet, while most of the patients who considered themselves much better found that it was necessary to continue on the recommended diet. They usually developed symptoms as soon as they ingested something containing azo dyes or benzoates.
  • Juhlin L, Michaëlsson G, and Zetterström O. Urticaria and asthma induced by food-and-drug additives in patients with aspirin hypersensitivity. Journal of Allergy and Clinical Immunology. 1972; 50(2): 92-98. ISSN 0091-6749. doi: 10.1016/0091-6749(72)90004-8. Read abstract:
    Seven of 8 recently investigated aspirin-sensitive patients reacted with asthma, urticaria, or both after 1 to 2 mg. of the azobenzene dye, tartrazine. Tartrazine is commonly used as a food and drug color and a daily intake of several milligrams is possible. The patients also reacted to some benzoic acid derivatives. All of these food-and-drug additives may be difficult to avoid. It is important, therefore, that they are properly identified since they are dangerous for certain patients with asthma and urticaria.


Coming soon


  • Shelley WB. 1964. Birch pollen and aspirin psoriasis: A study in salicylate hypersensitivity. JAMA. 189(13). doi:10.1001/jama.1964.03070130005001.
  • Zelickson BD, Muller SA. 1991. Generalized pustular psoriasis in childhood. Report of thirteen cases. J Am Acad Dermatol. 24(2 Pt 1):186–194. doi:10.1016/0190-9622(91)70025-w.


coming soon


Anderson J. Food-chemical intolerance in the breastfed infant. Breastfeed Rev. 2013;21(1):17–20. Read abstract:
The investigation of adverse food reactions can be complex and ideally should be guided and monitored by a dietitian experienced in the field. Maternal elimination diets require high motivation and must include all important nutrients.

Studies that promote hope for healing and treatments - please check with your doctor!

What can you consume for a treatment or management?

  • Cruz L, Castañeda-Hernández G, Navarrete A. Ingestion of chilli pepper (Capsicum annuum) reduces salicylate bioavailability after oral aspirin administration in the rat. Can J Physiol Pharmacol. 1999;77(6):441-446. View abstract:
    To my knowledge, there are no clinical studies on people demonstrating this concept works in humans. Please make note, that there is lots of research showing that animals (even when closely related) metabolize salicylates in different ways as shown in Protasiuk and Olejnik 2020 on aspirin consumption in chickens (listed below under food production).
  • Healy E, Newell L, Howarth P, Friedmann PS. 2008. Control of salicylate intolerance with fish oils. Br J Dermatol. 159(6):1368–1369. doi:10.1111/j.1365-2133.2008.08830.x.
    We report three patients with disabling salicylate-induced intolerance who experienced abrogation of symptoms following dietary supplementation with omega-3 polyunsaturated fatty acids (PUFAs). All three patients experienced severe urticaria, asthma requiring systemic steroid therapy and anaphylactic reactions. After dietary supplementation with 10 g daily of fish oils rich in omega-3 PUFAs for 6-8 weeks all three experienced complete or virtually complete resolution of symptoms allowing discontinuation of systemic corticosteroid therapy. Symptoms relapsed after dose reduction. Fish oil appears a safe and effective treatment for this difficult and often serious condition.
  • Moss M, Waring RH. 2003. The plasma cysteine/sulphate ratio: A possible clinical biomarker. J Nutr Environ Med. 13(4):215–229. doi:10.1080/13590840310001642003. Read full article at:
    Patients with chronic conditions including myalgic encephalomyelitis, irritable bowel syndrome, migraine, arthritis, multiple chemical sensitivity and depression are likely to benefit from tests for cysteine and sulphate, and from treatment designed to improve these levels. Oral fish oil, vitamin B2, pantothenate and molybdenum, and Epsom salt baths may help patients with low sulphate. Vitamins B2 and B6, zinc and magnesium, and a low protein diet may reduce high cysteine levels. N‐acetyl cysteine, zinc and vitamin C may help those with low cysteine levels. Patients with abnormal levels of sulphate might be counselled against working in polluted conditions, where efficient sulphate conjugation is required, and against using pesticides.

Metabolism of Salicylates

  • Badenhorst CPS, Erasmus E, van der Sluis R, Nortje C, van Dijk AA. 2014. A new perspective on the importance of glycine conjugation in the metabolism of aromatic acids. Drug Metab Rev. 46(3):343–361. doi:10.3109/03602532.2014.908903.
    In this review it will be argued that the major role of glycine conjugation is to dispose of the end products of phenylpropionate metabolism. Furthermore, glucuronidation, which occurs in the endoplasmic reticulum, would not be ideal for the detoxification of free benzoate, which has been shown to accumulate in the mitochondrial matrix. Glycine conjugation, however, prevents accumulation of benzoic acid in the mitochondrial matrix by forming hippurate, a less lipophilic conjugate that can be more readily transported out of the mitochondria. Finally, it will be explained that the glycine conjugation of benzoate, a commonly used preservative, exacerbates the dietary deficiency of glycine in humans. Because the resulting shortage of glycine can negatively influence brain neurochemistry and the synthesis of collagen, nucleic acids, porphyrins, and other important metabolites, the risks of using benzoate as a preservative should not be underestimated.

Broader Studies that can include Salicylates

Chemical Sensitivity

  • Steinemann, Anne. National Prevalence and Effects of Multiple Chemical Sensitivities, Journal of Occupational and Environmental Medicine: March 2018 - Volume 60 - Issue 3 - p e152-e156
    doi: 10.1097/JOM.0000000000001272. Full pdf available from:
    The aim of this study was to assess the prevalence of multiple chemical sensitivities (MCS), its co-occurrence with asthma and fragrance sensitivity, and effects from exposure to fragranced consumer products. Among the population, 12.8% report medically diagnosed MCS and 25.9% report chemical sensitivity. Of those with MCS, 86.2% experience health problems, such as migraine headaches, when exposed to fragranced consumer products; 71.0% are asthmatic; 70.3% cannot access places that use fragranced products such as air fresheners; and 60.7% lost workdays or a job in the past year due to fragranced products in the workplace. Prevalence of diagnosed MCS has increased over 300%, and self-reported chemical sensitivity over 200%, in the past decade. Reducing exposure to fragranced products could help reduce adverse health and societal effects.
  • Anne Steinemann. Prevalence and effects of multiple chemical sensitivities in Australia, Preventive Medicine Reports: Volume 10, 2018, Pages 191-194, ISSN 2211-3355, Full pdf available from:
    The aims of this study are to assess the prevalence of MCS, its overlaps with asthma and fragrance sensitivity, and its health and societal effects in Australia. Data were collected in June 2016 using an on-line survey with a representative national sample (N = 1098) of adults (ages 18–65) in Australia. Results found that, across the country, 6.5% report medically diagnosed MCS, 18.9% report chemical sensitivity (being unusually sensitive to everyday chemicals and chemically formulated products), and 19.9% either or both. Among people with MCS, 74.6% also have diagnosed asthma or an asthma-like condition, and 91.5% have fragrance sensitivity, reporting health problems (such as migraine headaches) when exposed to fragranced consumer products (such as air fresheners and cleaning supplies). In addition, among people with MCS, 77.5% are prevented from access to places because of fragranced products, 52.1% lost workdays or a job in the past year due to fragranced product exposure in the workplace, and 55.4% report health effects considered potentially disabling. Results indicate that MCS is a widespread disease, affecting an estimated 1 million adult Australians, with chemical sensitivity affecting another 2 million. Reducing chemical exposure to problematic sources, such as fragranced consumer products, is critical to reduce adverse effects.
  • Steinemann, A. Chemical sensitivity, asthma, and effects from fragranced consumer products: National Population Study in the United Kingdom. Air Qual Atmos Health 12, 371–377 (2019). Read full abstract at:
    This national study in the United Kingdom (UK) investigated the prevalence of chemical sensitivity, a condition associated with chemical pollutant exposures, and the medical diagnosis of multiple chemical sensitivities (MCS). In addition, it investigated the co-occurrence of chemical sensitivity with asthma and asthma-like conditions, and with fragrance sensitivity (adverse health effects from fragranced consumer products). Results indicate that chemical sensitivity is widespread in the UK, affecting over 5.7 million adults, with over 2.3 million diagnosed MCS, 8.9 million asthmatics, and 9.8 million fragrance sensitive. Reducing chemical exposure to problematic sources, such as fragranced consumer products, is a critical step to reduce adverse health and societal effects.
  • Steinemann, A. Chemical sensitivity, asthma, and effects from fragranced consumer products: national population study in Sweden. Air Qual Atmos Health 12, 129–136 (2019). Read full abstract from:
    Common chemical products and pollutants—such as pesticides, solvents, new building materials, and fragranced consumer products—have been associated with adverse health and societal effects. For some, the effects can be severe and disabling. This national population study in Sweden examined the prevalence and effects of chemical sensitivity, a condition characterized by health problems from chemical pollutant exposures. In addition, it examined the prevalence of medically diagnosed multiple chemical sensitivities (MCS), and the co-occurrence of chemical sensitivity with asthma and asthma-like conditions, and with fragrance sensitivity (health problems from fragranced consumer products). Results indicate that chemical sensitivity is a widespread condition, affecting more than 1 million adults in Sweden, with fragrance sensitivity affecting nearly 2 million. Reducing chemical exposure to problematic sources, such as fragranced consumer products, is critical to reduce adverse health and societal effects.

Food Production

  • Protasiuk, E., & Olejnik, M. (2020). Residues of salicylic acid and its metabolites in hen plasma, tissues and eggs as a result of animal treatment and consumption of naturally occurring salicylates. Food additives & contaminants. Part A, Chemistry, analysis, control, exposure & risk assessment, 37(6), 946–954. Abstract at:
    Study looks at salicylate levels in eggs, liver, and muscle meat after chickens are given salicylates in their drinking water over the course of seven days. Levels were tested intermittently over 72 hours. The exposure of hens to the salicylates at feed additive levels and to naturally occurring salicylates results in low residue concentrations and fast depletion of salicylic acid. The eggs do not pose any risk to consumers sensitive to salicylates.
  • Aghdam MS, Asghari M, Khorsandi O, Mohayeji M. 2014. Alleviation of postharvest chilling injury of tomato fruit by salicylic acid treatment. J Food Sci Technol. 51(10):2815–2820. doi:10.1007/s13197-012-0757-1. Full article at


Fragrance Studies

Also see Chemical Sensitivity since most of these overlap.

  • Goodman N, Nematollahi N, Steinemann A. 2020. Fragranced laundry products and emissions from dryer vents: implications for air quality and health. Air Qual Atmos Health. doi:10.1007/s11869-020-00929-0. Read abstract at:
    Fragranced laundry products emit numerous volatile organic compounds (VOCs), including terpenes such as limonene. Fragrance emissions have been associated with adverse health effects such as asthma attacks and breathing difficulties. Further, fragrance terpenes are primary indoor air pollutants that can react with other compounds and contribute to both indoor and outdoor air pollution. This paper examines volatile emissions and exposures from fragranced laundry products, and the implications for air quality and health.

  • Goodman NB, Wheeler AJ, Paevere PJ, Agosti G, Nematollahi N, Steinemann A. 2019. Emissions from dryer vents during use of fragranced and fragrance-free laundry products. Air Qual Atmos Health. 12(3):289–295. doi:10.1007/s11869-018-0643-8. Read full article:
    Fragranced laundry products emit a range of volatile organic compounds, including hazardous air pollutants. Exposure to fragranced emissions from laundry products has been associated with adverse health effects such as asthma attacks and migraine headaches. Little is known about volatile emissions from clothes dryer vents and the effectiveness of strategies to reduce concentrations and risks. This study investigates volatile emissions from six residential dryer vents, with a focus on d-limonene. It analyses and compares concentrations of d-limonene during use of fragranced and fragrance-free laundry products, as well as changes in switching from fragranced to fragrance-free products.

  • Steinemann AC, Gallagher LG, Davis AL, MacGregor IC. 2013. Chemical emissions from residential dryer vents during use of fragranced laundry products. Air Qual Atmos Health. 6(1):151–156. doi:10.1007/s11869-011-0156-1. Read abstract at:
    Common laundry products, used in washing and drying machines, can contribute to outdoor emissions through dryer vents. However, the types and amounts of chemicals emitted are largely unknown. To investigate these emissions, we analyzed the volatile organic compounds (VOCs) both in the headspace of fragranced laundry products and in the air emitted from dryer vents during use of these products. In a controlled study of washing and drying laundry, we sampled emissions from two residential dryer vents during the use of no products, fragranced detergent, and fragranced detergent plus fragranced dryer sheet. Our analyses found more than 25 VOCs emitted from dryer vents, with the highest concentrations of acetaldehyde, acetone, and ethanol. Seven of these VOCs are classified as hazardous air pollutants (HAPs) and two as carcinogenic HAPs (acetaldehyde and benzene) with no safe exposure level, according to the US Environmental Protection Agency. As context for significance, the acetaldehyde emissions during use of one brand of laundry detergent would represent 3% of total acetaldehyde emissions from automobiles in the study area.

  • Marín I, Sayas-Barberá E, Viuda-Martos M, Navarro C, Sendra E. 2016. Chemical composition, antioxidant and antimicrobial activity of essential oils from organic fennel, parsley, and lavender from Spain. Foods. 5(1):18. doi:10.3390/foods5010018. [accessed 2023 Apr 22]. Full text at: The aim of this work was to (i) determine the chemical composition of the essential oils of three spices widely cultivated in Spain from organic growth: Foeniculum vulgare, Petroselium crispum, and Lavandula officinalis; (ii) determine the total phenolic content; (iii) determine the antioxidant activity of the essentials oils by means of three different antioxidant tests and (iv) determine the effectiveness of these essentials oils on the inhibition of Listeria and Pseudomonas. This study shows that the main ingredients in Spanish organic lavender Essential oil was  linalool (34.44%) followed by linalyl acetate (34.19%) accounting up to 69% of the total composition. Neither of these chemicals are remotely close to a salicylate (fortunately). They did not show a line item for salicylates, It did talk a lot about phenols.

  • Nematollahi N, Ross PA, Hoffmann AA, Kolev SD, Steinemann A. 2021. Limonene emissions: Do different types have different biological effects? Int J Environ Res Public Health. 18(19):10505. doi:10.3390/ijerph181910505. [accessed 2022 Feb 28]. View full text:
    Limonene is one of the most abundant pollutants indoors, and it contributes to the formation of additional pollutants, such as formaldehyde and photochemical smog. Limonene is commonly used in fragranced consumer products, such as cleaning supplies and air fresheners, which have also been associated with health problems. Limonene can exist in different enantiomeric forms (R-limonene and S-limonene) and be derived from different sources. However, little is known about whether different forms and sources of limonene may have different effects. This research explored whether different types of limonene, at the same concentrations, could elicit different biological effects. To investigate this question, the study employed Aedes aegypti mosquitoes

  • Ross PA, Nematollahi N, Steinemann A, Kolev SD, Hoffmann AA. 2022. Differential toxicological effects of natural and synthetic sources and enantiomeric forms of limonene on mosquito larvae. Air Qual Atmos Health. 15(1):31–34. doi:10.1007/s11869-021-01106-7.  Full pdf:
    Common fragranced consumer products, such as cleaning supplies and personal care products, emit chiral compounds such as limonene that have been associated with adverse effects on human health. However, those same compounds abound in nature, and at similar concentrations as in products, but without the same apparent adverse human health effects. We investigated whether different types of limonene may elicit different biological effects.

  • Steinemann, Anne. Ten questions concerning fragrance-free policies and indoor environments. Building and Environment, Volume 159, 2019, 106054.
    Full pdf from:
    Indoor air quality is an international concern, linked with adverse effects on health and productivity. A common source of indoor air pollutants is fragranced consumer products, such as air fresheners, cleaning supplies, and personal care products. Exposure to fragranced products has been associated with health problems, such as breathing difficulties and migraine headaches, as well as lost workdays and loss of access in society. This paper presents and answers ten questions to explore fragrance-free policies within indoor built environments. Using a set of 60 fragrance-free policies, it analyzes who, what, where, when, why, and how policies are implemented. It then examines potential benefits of fragrance-free policies, such as avoided costs from illness and lost workdays, as well as challenges. The paper concludes with guidance and research directions for the future.
  • Steinemann, A. International prevalence of fragrance sensitivity. Air Qual Atmos Health 12, 891–897 (2019). Full pdf from:
    This study investigates effects of fragranced consumer products on the general population in four countries: United States, Australia, United Kingdom, and Sweden. Nationally representative population surveys (n = 1137; 1098; 1100; 1100) found that, across the four countries, 32.2% of adults (34.7%, 33.0%, 27.8%, 33.1% respectively) report fragrance sensitivity; that is, adverse health effects from fragranced consumer products. For instance, 17.4% report health problems from air fresheners or deodorizers, and 15.7% from being in a room cleaned with scented products. Commonly reported health problems include respiratory difficulties (16.7%), mucosal symptoms (13.2%), migraine headaches (12.6%), skin rashes (9.1%), and asthma attacks (7.0%). For 9.5% of the population, the severity of health effects can be considered disabling. Further, 9.0% of the population have lost workdays or lost a job, in the past year, due to illness from fragranced product exposure in the workplace. Personal estimated costs due to these lost workdays and lost jobs, across the four countries in one year, exceed $146 billion (USD). A majority of people across the countries would prefer that workplaces, health care facilities and professionals, hotels, and airplanes were fragrance-free rather than fragranced. The study highlights a concern for public health and societal well-being, as well as an approach to reduce risks and costs: reduce exposure to fragranced products.
  • Steinemann, A., Nematollahi, N., Rismanchi, B. et al. Pandemic products and volatile chemical emissions. Air Qual Atmos Health (2020). Full pdf available at:
    The recent pandemic (COVID-19) has seen a sweeping and surging use of products intended to clean and disinfect, such as air sprays, hand sanitizers, and surface cleaners, many of which contain fragrance. However, exposure to fragranced cleaning products has been associated with adverse effects on human health. Products can emit a range of volatile chemicals, including some classified as hazardous, but relatively few ingredients are disclosed to the public. Thus, relatively little is known about the specific emissions from these products. This study investigates the volatile organic compounds (VOCs) emitted from “pandemic products” that are being used frequently and extensively in society. In addition, among these emissions, this study identifies potentially hazardous compounds, compares so-called green and regular versions of products, and examines whether ingredients are disclosed to the public. All products emitted potentially hazardous compounds. Comparing regular products and green products, no significant difference was found in the emissions of the most prevalent compounds. Further, among the 399 compounds emitted, only 4% of all VOCs and 11% of potentially hazardous VOCs were disclosed on any product label or safety data sheet. This study reveals that pandemic products can generate volatile emissions that could pose risks to health, that could be unrecognized, and that could be reduced, such as by using fragrance-free versions of products.
  • Steinemann, A. The fragranced products phenomenon: air quality and health, science and policy. Air Qual Atmos Health (2020). Full pdf available at:
    This paper examines the issue of fragranced consumer products and its science and policy dimensions, with a focus on the implications for air quality and human health. Results include new findings and new questions for future research directions.
  • Steinemann, A. International prevalence of chemical sensitivity, co-prevalences with asthma and autism, and effects from fragranced consumer products. Air Qual Atmos Health 12, 519–527 (2019). Full pdf from:
    This study investigated the prevalence of chemical sensitivity in four countries—the United States (US), Australia (AU), Sweden (SE), and the United Kingdom (UK). In addition, it investigated the co-prevalence of chemical sensitivity with medically diagnosed multiple chemical sensitivities (MCS), fragrance sensitivity (health problems from fragranced products), asthma/asthma-like conditions, and autism/autism spectrum disorders (ASDs). Results found that, across the four countries, 19.9% of the population report chemical sensitivity, 7.4% report medically diagnosed MCS, 21.2% report either or both, and 32.2% report fragrance sensitivity. In addition, 26.0% of the population report asthma/asthma-like conditions, of which 42.6% report chemical sensitivity and 57.8% fragrance sensitivity. Also, 4.5% of the population report autism/ASDs, of which 60.6% report chemical sensitivity and 75.8% fragrance sensitivity. Among individuals with chemical sensitivity, 55.4% also report asthma/asthma-like conditions, 13.5% autism/ASDs, and 82.0% fragrance sensitivity. Although the prevalence of chemical sensitivity across the countries is statistically different, its co-prevalences with other conditions are statistically similar. Results also found that, for 44.1% of individuals with chemical sensitivity, the severity of health effects from fragranced products can be potentially disabling. Further, 28.6% of those with chemical sensitivity have lost workdays or a job, in the past year, due to exposure to fragranced products in the workplace. Results indicate that chemical sensitivity is widespread across the four countries, affecting over 61 million people, that vulnerable individuals such as those with asthma and autism are especially affected, and that fragranced consumer products can contribute to the adverse health, economic, and societal effects.
  • Steinemann, A., Nematollahi, N. Migraine headaches and fragranced consumer products: an international population-based study. Air Qual Atmos Health 13, 387–390 (2020). Read abstract:
    Fragranced consumer products, such as air fresheners and cleaning supplies, have been associated with health problems including migraine headaches. This study investigates the prevalence of migraines associated with exposure to fragranced products. Nationally representative population surveys (n = 4435) across four countries—the United States (US), Australia (AU), the United Kingdom (UK), and Sweden (SE)—found that, on average, 12.6% of adults report migraine headaches when exposed to fragranced products (15.7% US, 10.0% AU, 8.4% UK, 16.1% SE). Among those individuals, 43.2% report migraines from air fresheners or deodorizers, 15.0% from the scent of laundry products coming from a dryer vent, 39.9% from being in a room cleaned with scented products, 53.7% from being near someone wearing a fragranced product, and 45.7% from other types of fragranced products. Furthermore, 30.6% of these individuals have lost workdays or lost a job, in the past year, due to fragranced product exposure in the workplace. Findings from this study indicate that migraine headaches can be associated with fragranced consumer products, and that reducing exposure could reduce adverse health and societal effects.
  • Steinemann, A., Goodman, N. Fragranced consumer products and effects on asthmatics: an international population-based study. Air Qual Atmos Health 12, 643–649 (2019). Read full article:
    This study investigates the health and societal effects of fragranced products on asthmatics in four countries: United States, Australia, United Kingdom, and Sweden. Nationally representative population surveys (n = 1137; 1098; 1100; 1100) found that, across the four countries, 26.0% of adults (n = 1151) are asthmatic, reporting medically diagnosed asthma (15.8%), an asthma-like condition (11.1%), or both. Among these asthmatics, 57.8% report adverse health effects, including asthma attacks (25.0%), respiratory problems (37.7%), and migraine headaches (22.6%), from exposure to fragranced products. In particular, 36.7% of asthmatics report health problems from air fresheners or deodorizers, 18.1% from the scent of laundry products coming from a dryer vent, 32.9% from being in a room cleaned with scented products, 38.7% from being near someone wearing a fragranced product, and 37.5% from other types of fragranced products. For 24.1% of asthmatics, health problems from fragranced products are potentially disabling. Further, 20.6% of asthmatics have lost workdays or lost a job, in the past year, due to fragranced product exposure in the workplace. Fragrance-free environments received widespread support. More than twice as many individuals, both asthmatics as well as non-asthmatics, would prefer that workplaces, health care facilities and professionals, airplanes, and hotels were fragrance-free rather than fragranced. This study provides evidence that asthmatics can be profoundly, adversely, and disproportionately affected by exposure to fragranced consumer products. Moreover, the study points to a relatively straightforward and cost-effective approach to reduce risks; namely, to reduce exposure to fragranced products.
  • Steinemann, A. Fragranced consumer products: effects on asthmatics. Air Qual Atmos Health 11, 3–9 (2018). Full pdf available at:
    This study investigates the prevalence and types of effects of fragranced products on asthmatics in the American population. Using a nationally representative sample (n = 1137), data were collected with an on-line survey of adults in the USA, of which 26.8% responded as being medically diagnosed with asthma or an asthma-like condition. Results indicate that 64.3% of asthmatics report one or more types of adverse health effects from fragranced products, including respiratory problems (43.3%), migraine headaches (28.2%), and asthma attacks (27.9%). Overall, asthmatics were more likely to experience adverse health effects from fragranced products than non-asthmatics (prevalence odds ratio [POR] 5.76; 95% confidence interval [CI] 4.34–7.64). In particular, 41.0% of asthmatics report health problems from air fresheners or deodorizers, 28.9% from scented laundry products coming from a dryer vent, 42.3% from being in a room cleaned with scented products, and 46.2% from being near someone wearing a fragranced product. Of these effects, 62.8% would be considered disabling under the definition of the Americans with Disabilities Act. Yet 99.3% of asthmatics are exposed to fragranced products at least once a week. Also, 36.7% cannot use a public restroom if it has an air freshener or deodorizer, and 39.7% would enter a business but then leave as quickly as possible due to air fresheners or some fragranced product. Further, 35.4% of asthmatics have lost workdays or a job, in the past year, due to fragranced product exposure in the workplace.
  • Steinemann, A., Wheeler, A.J. & Larcombe, A. Fragranced consumer products: effects on asthmatic Australians. Air Qual Atmos Health 11, 365–371 (2018).  View full pdf at:
    This study investigated the prevalence and types of health problems associated with exposure to fragranced products among asthmatic Australians. Nationally representative cross-sectional data were obtained in June 2016 with an online survey of adult Australians (n = 1098), of which 28.5% were medically diagnosed with asthma or an asthma-like condition. Nationally, 55.6% of asthmatics, and 23.9% of non-asthmatics, report adverse health effects after exposure to fragranced products. Specifically, 24.0% of asthmatics report an asthma attack. Moreover, 18.2% of asthmatics lost workdays or a job in the past year due to fragranced products in the workplace. Over 20% of asthmatics are unable to access public places and restrooms that use air fresheners. Exposure to fragranced products is associated with health problems, some potentially serious, in an estimated 2.2 million asthmatic adult Australians. Asthmatics were proportionately more affected than non-asthmatics (prevalence odds ratio 3.98; 95% confidence interval 3.01–5.24).
  • Steinemann, A. Fragranced consumer products: effects on autistic adults in the United States, Australia, and United Kingdom. Air Qual Atmos Health 11, 1137–1142 (2018). Full pdf article available at:
    This study investigates the effects of fragranced products on autistic individuals ages 18–65 in the United States, Australia, and United Kingdom. Nationally representative population surveys (n = 1137; 1098; 1100) found that, across the three countries, 4.3% of adults (n = 142) report medically diagnosed autism (2.3%), an autism spectrum disorder (2.4%), or both. Of these autistic adults, 83.7% report adverse health effects from fragranced products, including migraine headaches (42.9%), neurological problems (34.3%), respiratory problems (44.7%), and asthma attacks (35.9%). In particular, 62.9% of autistic adults report health problems from air fresheners or deodorizers, 57.5% from the scent of laundry products coming from a dryer vent, 65.9% from being in a room cleaned with scented products, and 60.5% from being near someone wearing a fragranced product. Health problems can be severe, with 74.1% of these effects considered potentially disabling under legislation in each country. Further, 59.4% of autistic adults have lost workdays or lost a job, in the past year, due to fragranced product exposure in the workplace.
  • More articles by Dr. Anne Stinemann


Related Medical Conditions

Aspirin "Allergy" of NSAID Allergy

  • Are those who have aspirin or NSAID allergy also allergic to Bismuth subsalicylate which are the ingredients of "Pepto- Bismol"?
    Explaining AERD/NERD and COX-1 Inhibition issues. Explains how aspirin allergy is not a true allergy, and how people are actually affected.
  • Is it Possible to be Allergic to Aspirin? AAAAI:
    Explains that it is possible to have a true allergy to aspirin, but only explains the more common version which is a sensitivity. An allergic-type reaction is probably the best way to explain it.  Also covers that a person can be sensitive to aspirin, NSAIDS, and tylenol, and another person may only be sensitive to one of them.
  • Feinman SE. Beneficial and Toxic Effects of Aspirin. Boca Raton: CRC Press; 1994. (book)
    130 pages - Beneficial effects -- History, uses, labeling and poison prevention packaging by Bharat Bhooshan; Prostaglandins, other lipid mediators and the mechanism of action of aspirin by Adam K. Myers, Peter W. Ramwell; Risks -- Aspirin toxicity by Susan E. Feinman; Aspirin and gastrointestinal toxicity by Susan E. Feinman; Aspirin sensitivity in the respiratory system by Donald D. Stevenson; Aspirin-related urticaria and angioedema by Emil J. Bardana, Jr., Anthony Montanaro; Benefit-risk assessment -- Role of aspirin in chemoprevention of cancer and its effect on mutagenicity by Susan E. Feinman; Effects of aspirin on female reproductive function and on in utero development by Irva Hertz-Picciotto; Biochemical manifestations of Reye Syndrome: the role of aspirin by Laurie E. Kilpatrick; Aspirin and the elderly: therapeutic implications by Jacob Karsh; Veterinary use and misuse by Thomas R.B. Barr.
  • Speer F. Aspirin allergy: a clinical study. Southern medical journal. 1975;68(3):314-318. Abstract:
    The following beliefs about aspirin sensitivity are widely held: (1) it usually is accompanied by nasal polyps. (2) It occurs primarily in nonallergic patients. (3) Its most common manifestation is asthma. (4) When it is combined with polyps and asthma (the so-called "aspirin triad"), the prognosis is unfavorable. (5) Polypectomy may precipitate asthma in aspirin sensitive patients. This paper, based on a study of 112 private patients, presents clinical evidence to refute these beliefs. It shows the following: (1) Aspirin allergy is accompanied by polyps in less than 5% of cases (13% of asthma patients). (2) In most cases, patients show well-defined allergy to an inhalant, food, or other drug. (3) Its most common manifestations are urticaria and angiodema, not asthma. (4) The prognosis is favorable, whether or not polyps are present. (5) Polypectomy does not precipitate asthma in aspirin-sensitive patients.

MCAS - Mast Cell Activation Syndrome

  • AAAAI, Mast Cell Activation Syndrome (MCAS):

Dust Mite & Mite Oral Allergy Syndrome

  • Erben A, Rodriguez J, Mccullough J, Ownby D. 1993. Anaphylaxis after ingestion of beignets contaminated with Dermatophagoides farinae. J Allergy Clin Immunol. 92(6):846–849. doi:10.1016/0091-6749(93)90062-k.
    Case study of a man who ingested mites in his flour mix and ended up with anaphylaxis. This is the first reported case study of oral allergy syndrome from mite ingestion. I covered a full video on this:

  • Portnoy, Jay & Miller, Jeffrey & Williams, P. & Chew, Ginger & Miller, J. & Zaitoun, Fares & Phipatanakul, Wanda & Kennedy, Kevin & Barnes, Charles & Grimes, Carl & Larenas-Linnemann, Désirée & Sublett, James & Bernstein, David & Blessing-Moore, Joann & Khan, David & Lang, David & Nicklas, Richard & Oppenheimer, John & Randolph, Christopher & Wallace, Dana. (2013). Environmental assessment and exposure control of dust mites: a practice parameter. Annals of Allergy, Asthma & Immunology. 111. 465–507. Full text:
    For reasons that are not clear, many patients with dust mite allergy, and dust mite oral allergy syndrome have coexisting aspirin sensitivity. One study showed a recent review counting 59 of the 135 (43.7%) of the total reported patients as being sensitive to nonsteroidal anti-inflammatory drugs.
  • Kupczyk M, Kupryś I, Górski P, Kuna P. 2004. Aspirin intolerance and allergy to house dust mites: important factors associated with development of severe asthma. Ann Allergy Asthma Immunol. 92(4):453–458. Read abstract from:
    The data from this study show that aspirin intolerance, House dust mite allergy, and asthma duration exceeding 10 years are major factors associated with severe asthma in outpatients.
  • Popescu F-D. 2015. Cross-reactivity between aeroallergens and food allergens. World J Methodol. 5(2):31–50. doi:10.5662/wjm.v5.i2.31. Read full article at:
    Many different syndromes and associations due to cross-reactivity between aeroallergens and food allergens of plant, fungal and animal origin have been described. Significant examples are pollen-food syndromes or associations, along with mite-shrimp, cat-pork, and bird-egg syndromes, but rare or more complex clinical entities must also be discussed.

  • Tuano KTS, Davis CM. 2018. Oral allergy syndrome in shrimp and house dust mite allergies. J Allergy Clin Immunol Pract. 6(6):2163–2164. doi:10.1016/j.jaip.2018.04.035. Abstract at:
    Pollen food allergy syndrome is due to cross-reactivity between plant inhalant and food allergens, causing self-limited oropharyngeal mucosal symptoms. Clinicians should be aware of mite shrimp allergy syndrome with similar symptoms due to cross-reactivity of invertebrate inhalant and food allergens. (Not about salicylates, but that allergy of inhalants (dust mites) and food sensitivity/allergy can happen, and it's not limited to pollen only.)

Salicylism / Salicylate Poisoning

  • Mühlebach S, Steger P, Conen D, Wyss PA. 1996. Successful therapy of salicylate poisoning using glycine and activated charcoal. Schweiz Med Wochenschr. 126(49):2127–2129.
    Acute intoxications with salicylates are common. In a dosage of 150-300 mg/kg they are severe, and above 500 mg/kg potentially fatal. To commit suicide 4 patients ingested 375-460 mg/kg acetylsalicylic acid; 3-8 hours after ingestion salicylate blood levels of up to 760 mg/l were observed. The patients were treated for a period of 16 hours with oral charcoal and glycine (1 g/kg initially, followed every 4 hours by 0.5 g/kg, and 8 g initially, followed by 4 g, respectively). To increase urinary pH (7-9) they received i.v. NaHCO3. Blood levels of salicylic acid including its metabolites dropped initially with a virtual half-life of 2-4 hours. 18 hours after hospital admission every patient was in good general condition; none of them required hemodialysis. The urinary excretion of total salicylate reached only 6-14% of the dose within the first 12 hours of therapy, clearly indicating the importance of combined therapy with glycine and charcoal in achieving a good clinical outcome.

GI Disorders and Leaky Gut

Unsorted Articles

These articles are unsorted and have not been reviewed by me. They are references from Sharla Race's book "The Salicylate Handbook". This isn't all of them, but a good chunk. As I look through them, I will add them to different useful categories.

Unsorted articles

  1. Alberti A, Pirrone P, Elia M, Waring RH, Romano C. 1999. Sulphation deficit in “low-functioning” autistic children: a pilot study. Biol Psychiatry. 46(3):420–424.
    Background: Parents of autistic children and autism support groups often report that autistic episodes are exacerbated when the children eat certain foodstuffs such as dairy products, chocolates, wheat, corn sugar, apples, and bananas. The hypothesis that autistic behavior might be related to metabolic dysfunctions has led us to investigate in a group of “low functioning” autistic children and in an age-matched control group each made up of 20 subjects, the sulphation capacity available.
    Methods: Utilizing the biochemical characteristics of paracetamol we evaluated by high performance liquid chromatography, the urine paracetamol–sulfate/paracetamol-glucuronide (PS/PG) ratio in all subjects following administration of this drug.
    Results: The PS/PG ratio in the group of autistic subjects gave a significantly lower result than the control group with p < .00002.
    Conclusions: The inability to effectively metabolize certain compounds particularly phenolic amines, toxic for the CNS, could exacerbate the wide spectrum of autistic behavior.
  2. Allen DH, Van Nunen S, Loblay R, Clarke L, Swain A. 1984. Adverse reactions to foods. Med J Aust. 141(SP5):S37-42.
    The discovery of IgE in the mid-1960s resulted in a widespread view that allergy was the basis of most adverse reactions to food, but it is becoming increasingly clear that other, as yet poorly understood, mechanisms are responsible in the overwhelming majority of cases. This, together with the proliferation of popular literature on "food allergy" has resulted in considerable confusion in the minds of both the public and the medical profession on the subject. In the majority of patients presenting with food intolerance, recognized or otherwise, symptoms are precipitated by various small, non-immunogenic organic molecules present in the food as natural or added ingredients. These reactions are pharmacological rather than immunological in nature, although in some situations they may share a final common pathway with true allergic reactions, resulting in similar symptoms.
  3. A. AG, B. CG, J SG. 2004. Development of a rapid method based on solid-phase extraction and liquid chromatography with ultraviolet absorbance detection for the determination of polyphenols in alcohol-free beers. Journal of Chromatography A. 1054:175–180.
    An analytical method based on solid-phase extraction (SPE) and followed by liquid chromatographic separation and ultraviolet detection (HPLC-UV) is proposed for the determination of 10 phenolic compounds which participate on beer stability and sensory properties in alcohol-free beers. Acetonitrile was found to be the most appropriate solvent for the elution of polyphenolic compounds adsorbed on C18 cartridges. The performance of the method was assessed by the evaluation of parameters such as absolute recovery (generally higher than 60%), repeatability (lower than 10%), linearity (r2 higher than 0.993) and limits of quantitation (ranging from 1 to 37 microg/L); no matrix effects were observed. The polyphenol content of different Spanish alcohol-free beers is presented. Five phenolic compounds such as protocatechuic, p-coumaric, ferulic, caffeic acids, and (+)-catechin were identified at levels lower than 10 mg/L.
  4. Alonso-Aperte E, Varela-Moreiras G. 2000. Drugs–nutrient interactions: a potential problem during adolescence. Eur J Clin Nutr. 54(S1):S69–S74.
    The concept of drug-nutrient interactions is not new, but it has only recently gained currency in medicine. Although the elderly are normally considered to be at particular risk, other groups may also be at risk: infants, adolescents, pregnant women, alcohol and tobacco users, etc. In infants and adolescents there are several factors that may influence the possible interactions: firstly, nutrient needs are usually higher, mainly micronutrients; systems for detoxification of anutrients are not complete; the tendency to restricted diets (especially girls) that are unable to cover the actual recommended intakes for a number of micronutrients (i.e. vitamins); and the dangerous increase in alcohol consumption either in males or females. Administration of drugs in population with adequate vitamin intake is usually not a problem, but administration of drugs in those with borderline intake of vitamins or in patients with low nutritional status can result in symptomatic vitamin deficiency states. The groups at risk of poor vitamin status are smokers (a high proportion of adolescents are active smokers); dieters (skipping meals and dieting to lose weight frequently compromise micronutrient intake, and it should be considered that it is extremely difficult to meet all the requirements at intakes of less than 1,200 calories per day), oral contraceptive users, and pregnant and lactating women, excessive alcohol users, etc. The chapter also focuses on the case of folate: rapidly dividing tissues during the adolescent growth spurt increase requirements for folate. Because of this increased need, folate status appears to be of concern during the age of this rapid growth. A variety of drugs are known to interfere with vitamin utilization by blocking or altering transformation of the vitamin to its metabolically active form. Serum folate levels are known to be low in a high percentage of patients with rheumatoid arthritis, suggesting that aspirin alters the transport of folate by competition for binding sites on serum proteins. Methotrexate, a drug commonly used at low doses for the treatment of psoriasis, rheumatoid arthritis and certain liver disorders, limits the availability of methyl groups derived from one-carbon metabolism by inhibiting competitively a key enzyme in the intracellular folate metabolism. In humans, the antiepileptic drug valproic acid (VPA) is associated with two major adverse effects: teratogenicity and folate deficiency. The mechanisms by which VPA exerts the teratogenic or antifolate effect remain unclear, but an alteration in the methionine cycle is the strongest hypothesis proposed.
  5. Cuesta EA, Sánchez RA, Martín TS, Turrientes MA, Rodríguez DG. 1981. Pharmaceutical preparations which contain tartrazine. Allergologia et immunopathologia. 9(1):45–54.
    Allergic reactions to food colors have been known since 1958. Reactions to tartrazine, our example, include generalized pruritus, urticaria, angioedema, paresthesias, vomiting, migraine, rhinorrhea and nasal obstruction, coughing, asthma attacks and purpura. Many patients who are allergic to antiinflammatory drugs such as acetyl-salicylic acid and indomethacin show cross-reaction to tartrazine. Doses producing these reactions range from minimal amounts up to 750 mg. Symptoms appear after periods of time ranging from minutes to 6 to 14 hours. In view of these facts (some of which represent a threat to the patient's life), additives, colouring matter, etc, do not usually appear in product labels or specifications, or in handbooks or catalogues used in practice. We drew up a list of drugs which may contain food dyes and coloring matter, yellow No. 5. A letter was written to 233 laboratories of which 159 (68%) replied. 72 (45%) in the affirmative and 87 (55%) in the negative, 74 (32%) did not reply.
  6. Ambanelli U, Ferraccioli GF, Serventi G, Vaona GL. 1982. Changes in serum and urinary zinc induced by ASA and Indomethacin. Scand J Rheumatol. 11(1):63–64.
  7. Anderson RJ, Potts DE, Gabow PA, Rumack BH, Schrier RW. 1976. Unrecognized adult salicylate intoxication. Ann Intern Med. 85(6):745–748.
    Adult salicylate intoxication has been considered to be easily recognized and associated with low morbidity and mortality. In the present study of 73 consecutive adults hospitalized with salicylate intoxication, 27% of patients were undiagnosed for as long as 72 h after admission. The initial physical findings and laboratory data in patients not diagnosed on admission did not markedly differ from the findings in patients diagnosed on admission, and included tachypnea and acid-base disturbances as well as the frequent occurrence of neurologic abnormalities. However, patients with a delayed diagnosis of salicylate intoxication were older, rarely had a previous history of drug overdose, and more often became accidentally intoxicated while ingesting salicylate for associated medical illnesses when compared with patients diagnosed on admission. Mortality was encountered with significantly greater frequency in patients with delayed diagnosis, and, consequently, delayed therapy, when compared with patients diagnosed on admission.
  8. Baggott M, Heifets B, Jones RT, Mendelson J, Sferios E, Zehnder J. 2000. Chemical analysis of ecstasy pills. JAMA. 284(17):2190.
  9. Bailey RB, Jones SR. 1989. Chronic salicylate intoxication: a common cause of morbidity in the elderly. Journal of the American Geriatrics Society. 37(6):556–561.
    We reviewed the clinical profile of adults with chronic salicylate intoxication by evaluating the experience of our community teaching hospital between 1977 and 1987. Data on similar patients reported was obtained from an English-language literature search using MEDLINE (1966-88) and bibliographic reviews of textbooks and review articles. We also examined the impact of education and incentive on increasing the awareness and ability of physicians to diagnose the disorder. Chronic salicylate intoxication was defined by 1) a compatible clinical syndrome; 2) a serum level in the toxic range; and 3) improvement with withdrawal of the drug. Patients with chronic salicylism represent a cross-section of an elderly population. Our review suggests that diminished body mass, concurrent administration of drugs and conditions which exacerbate renal insufficiency may predispose to salicylate intoxication; however, few specific precipitants of chronic salicylism were recognized. Salicylate intoxication should be considered in all elderly patients with delirium and/or dementia.
  10. Ballmer-Weber BK, Widmer M, Burg G. 1993. Acetylsalicylic acid-induced generalized pustulosis. Schweiz Med Wochenschr. 123(12):542–546.
    We report the case of a 55-year-old patient with recurrent episodes of generalized pustulosis and febrile temperatures. Histological examination revealed subcorneal and spongiform pustules. After a 4 years' course acute exanthematous generalized pustulosis, induced by acetylsalicylic acid was diagnosed. Clinical features, differential diagnosis and causative agents of this rare drug reaction are discussed.
  11. Bamforth KJ, Jones AL, Roberts RC, Coughtrie MW. 1993. Common food additives are potent inhibitors of human liver 17 alpha-ethinyloestradiol and dopamine sulphotransferases. Biochem Pharmacol. 46(10):1713–1720.
    Interactions between dietary xenobiotics, drugs and biologically active endogenous compounds are a potential source of idiosyncratic adverse pathology. We have examined the inhibition of the sulphation of a number of xenobiotics and endobiotics in human liver cytosol by 15 food additives and constituents. Sulphation of dehydroepiandrosterone was resistant to inhibition by all compounds tested; however, dopamine sulphotransferase (ST) activity was inhibited strongly by (+/-)-catechin, (+)-catechin, octyl gallate, tartrazine and vanillin. Sulphation of the xenobiotic steroid 17 alpha-ethinyloestradiol (EE2) was inhibited by vanillin, erythrosin B and octyl gallate. Of these compounds, only vanillin was found to be sulphated to a significant extent by both human liver and platelets, and vanillin was determined to be a substrate for the monoamine-sulphating isoenzyme of phenolsulphotransferase. Vanillin was found to inhibit 50% of liver EE2 ST activity (IC50) at a concentration of approximately 1.3 microM and the mode of inhibition was non-competitive. The implications of these results for the adverse side effects associated with food additives and oral contraceptives are discussed.
  12. Baranczyk-Kuzma A, Sawicki J. 1997. Biotransformation in monkey brain: coupling of sulfation to glutathione conjugation. Life Sci. 61(18):1829–1841.
    Phenol sulfotransferase (PST, EC and glutathione-S-transferase (GST, EC, the phase II biotransformation enzymes inactivate many exo- and endogenous compounds. The effect of PST substrates (catecholamines, simple phenols, selected phenolic drugs) and PST products (phenolic sulfates) on GST activity was investigated to identify possible interactions between sulfation and glutathione conjugation in the brain. Two soluble forms of PST and two forms of GST were isolated from monkey (Rhesus macacus) brain cortex. Catecholamines, hypertensive and hypotensive drugs which are sulfated by monkey brain PSTs slightly inhibit the activity of brain GSTs. The greatest inhibitory effect was observed with neurotoxic compounds such as 6-OHDA and manganese. The commonly used analgesic drugs inhibit both GST forms. These enzymes are also inhibited by phenacetin, the precursor of paracetamol, and prototype salicylates such as sodium salicylate and acetylsalicylic acid. The effect of simple phenols and their sulfated metabolites on GST activity varies. The obtained results point to a possible interaction between sulfation and glutathione conjugation in vivo since many physiologically, therapeutically and toxicologically active compounds which are sulfated by brain phenol sulfotransferases may be bound by brain glutathione-S-transferases. These compounds may lose their activity (on being bound to GST) and expose the brain to the toxic electrophiles (by decreasing GST activity).
  13. Bauer CA, Brozoski TJ, Holder TM, Caspary DM. 2000. Effects of chronic salicylate on GABAergic activity in rat inferior colliculus. Hear Res. 147(1–2):175–182.
    It is well accepted that salicylate ototoxicity results in reversible tinnitus in humans. Salicylate-induced tinnitus may be an example of plasticity of the central auditory system and could potentially serve as a model to further understand mechanisms of tinnitus generation. This study examined levels of glutamic acid decarboxylase (GAD) and the binding characteristics of the GABA(A) receptor in auditory brainstem structures of Long-Evans rats chronically treated with salicylate. Western blotting revealed a significant 63% (P<0.008) elevation of GAD levels in the inferior colliculus (IC) of salicylate-treated subjects. This occurred in subjects demonstrating behavioral evidence of tinnitus. Muscimol saturation analysis was indicative of a salicylate-related increase in receptor affinity. Linear regression of [(3)H]muscimol saturation analysis data revealed a significant (P<0.05) reduction in K(d) values in whole IC (-48%), as well as in the central nucleus of IC (CIC, -58%) and combined external and dorsal cortex of IC (E/DCIC, -46%). The number of GABA(A) binding sites (B(max)) were also significantly (P<0.05) decreased. These changes were observed only in central auditory structures. This suggests that GAD expression and GABA(A) receptor binding characteristics may be altered with chronic exposure to sodium salicylate and these changes may represent aberrant plasticity clinically experienced as tinnitus.
  14. Behl PN, Captain RM. 1979. Skin-irritant and sensitizing plants found in India.
    This edition was written for the practitioner and the dermatologist. It is a compilation of 270 plants and is illustrated with numerous sketches to help the practitioner identify the offending specimen. Each plant is listed by its botanical name, along with a brief bontanical description. The chemical constituents found in the specimens are discussed, and a description of the dermatoses they produce is given. The text outlines the mechanisms by which plants produce irritation. There are numerous tables that are helpful to the reader, in that they outline offending plants encountered in various occupational sites such as gardens, kitchens, orchards, farms, nurseries, commercial plantations, pharmacies, and perfumeries. The book is well indexed for both botanical and vernacular names and includes a short glossary of botanical terms for the practitioner who has little botanical training. This compilation of botanical and dermatologic information meets the working needs of the practitioner.
  15. Bekatorou AP, Koutinas C, A A. 2006. Production of food grade yeasts Food. Technology and Biotechnology. 44(3):407–415.
    Yeasts have been known to humans for thousands of years as they have been used in traditional fermentation processes like wine, beer and bread making. Today, yeasts are also used as alternative sources of high nutritional value proteins, enzymes and vitamins, and have numerous applications in the health food industry as food additives, conditioners and flavouring agents, for the production of microbiology media and extracts, as well as livestock feeds. Modern scientific advances allow the isolation, construction and industrial production of new yeast strains to satisfy the specific demands of the food industry. Types of commercial food grade yeasts, industrial production processes and raw materials are highlighted. Aspects of yeast metabolism, with respect to carbohydrate utilization, nutritional aspects and recent research advances are also discussed.
  16. Bhatia MS. 2000. Allergy to tartrazine in psychotropic drugs. J Clin Psychiatry. 61(7):473–476.
    Background: High psychiatric morbidity has been reported among those who complain of food intolerance or allergy. Many cases of food allergy or intolerance to drugs are not due to allergy to the food or drugs themselves, but to the additives used for coloring, flavoring, preserving, thickening, emulsifying, or stabilizing the product. Of various coloring dyes used, tartrazine (FD & C yellow no. 5) is the color most frequently incriminated in producing allergic reactions. The exact epidemiology and pattern of allergic reactions to tartrazine in psychotropic drugs have not been frequently studied and reported.
    Method: The present study included consecutive outpatients (May 1996 to April 1998) who developed allergic reactions or intolerance to tartrazine in psychotropic drugs. Total patients exposed to tartrazine-containing drugs were also recorded. The subjects showing allergic reactions to tartrazine were then exposed to non-tartrazine-containing brands.
    Results: Of 2210 patients exposed to tartrazine-containing drugs, 83 (3.8%) developed allergic reactions. The symptoms subsided within 24 to 48 hours of stopping the drug. None of the patients showed allergy to non-tartrazine-containing brands. History of allergy to tartrazine was present in 13.2%, and 15.7% of patients had a history of aspirin sensitivity.
    Conclusion: Tartrazine allergy should be considered in patients developing drug allergy, because it would require changing the brand rather than stopping treatment with that drug.
  17. Binkley NC, Krueger DC, Engelke JA, Foley AL, Suttie JW. 2000. Vitamin K supplementation reduces serum concentrations of under-gamma-carboxylated osteocalcin in healthy young and elderly adults. Am J Clin Nutr. 72(6):1523–1528.
    Background: Subclinical vitamin K insufficiency, manifested by under-gamma-carboxylation of the bone matrix protein osteocalcin, may be common.
    Objective: Our objective was to delineate the prevalence of submaximal gamma-carboxylation as assessed by response to phylloquinone supplementation and to evaluate the effect of this intervention on skeletal turnover in healthy North American adults.
    Design: Healthy subjects (n = 219), approximately equally distributed by sex and age (18-30 y and >/=65 y), received daily phylloquinone (1000 microg) or placebo for 2 wk. Serum undercarboxylated osteocalcin (ucOC) and total osteocalcin, N:-telopeptides of type I collagen (NTx), bone-specific alkaline phosphatase (BSAP), and phylloquinone concentrations were measured at baseline and after weeks 1 and 2.
    Results: At baseline, the mean serum phylloquinone concentration was lower in the young than in the old group; there was no effect of sex. Concomitantly, baseline %ucOC was highest in the young and lowest in the old men (P: < 0.0001) but did not differ significantly by age in women. After supplementation, serum phylloquinone concentration increased approximately 10-fold (P: < 0.0001) at week 1 (from 0.93 +/- 0.08 to 8.86 +/- 0.70 nmol/L, x+/- SEM); this was sustained through week 2. Among all supplemented groups, mean %ucOC decreased from 7.6% to 3. 4% without significant differences by age or sex; 102 of 112 subjects had a >1% decrease. Phylloquinone supplementation reduced serum osteocalcin but did not alter NTx or BSAP concentration.
    Conclusions: Usual dietary practices in this population did not provide adequate vitamin K for maximal osteocalcin carboxylation. Phylloquinone supplementation reduced serum osteocalcin concentration but did not alter other markers of serum bone turnover.
  18. Botey J, Navarro C, Aulesa C, Marín A, Eseverri JL. 1988. Acetyl salicylic acid induced-urticaria and/or angioedema in atopic children. Allergol Immunopathol (Madr). 16(1):43–47.
    From the report of Hirschberg, only 3 years after aspirin synthesis, there have been numerous works dedicated to showing the different types of adverse reactions found following aspirin administration. However, there are few publications on the process of urticaria and/or acute angioedema induced by ASA and few reported cases were found in children. Thus, we present 6 atopic children with urticaria and/or angioedema related with ASA. A carefully detailed history, oral provocation with ASA, oral provocation with other NSAI and HBDT with ASA were done to all of them. The oral provocation with ASA was positive in 5 of the 6 cases. The provocations with the rest of the NSAI and tartrazine and sodium benzoate were negative in all of the patients. The HBDT was positive in 5 of the cases. In conclusion, we insist that aspirin intolerance is not infrequent in infancy and it is not rare to see urticaria and or angioedema, in spite of the fact that asthmatics, atopics or non atopics, usually present as bronchospasm. We also believe that the HBDT can be a method of diagnosis used in these cases.
  19. Breakey J, Hill M, Reilly C, Connell H. 1991. Report of a trial of the low additive, low salicylate diet in the treatment of behaviour and learning problems in children. Aust J Nutr Diet. 48:89–94.
    Five hundred and sixteen children attending a metropolitan child psychiatry service trialed a low additive low salicylate (LALS) diet as part of management of behavioural and learning problems. The mean age was 7.8 years; 85% were males. A positive response was obtained in 79.5% of children with a normal range of behaviour achieved in 54.5% of the 25% in whom diet was necessary but not sufficient; half also required stimulant medication. Non-responders were 9.3%, those not available to follow up were 8.7% and those not implementing the treatment 2.5%. As well almost 50% limited or excluded other foods, particularly chocolate, milk and wheat. Amongst presenting problems change occurred in behaviour, social, learning, activity, sleep and allergic problems. There was no gender effect, but an age effect was evident with the proportion of responders in the under nine group being significantly higher. If there was a family history of allergy, and where there was intolerance to any food, the likelihood of a positive outcome was higher, but outcome was not affected by a belief that food affected the child. Additives and salicylates are better thought of as aggravating the underlying predisposition in susceptible children, rather than as causative agents.
  20. Breakey J. 1978. Dietary management of hyperkinesis and behavioural problems. Aust Fam Physician. 7(6):720–724.
    The approach to the Feingold diet need be no different from that of well-established dietary regimes. Of the group studied, the benefits far outweighed the effort involved in many families. The potential of treatment of these disorders with dietary intervention must be considered as a part of their overall management.
  21. Brenner A. 1977. A study of the efficacy of the Feingold diet on hyperkinetic children. Some favorable personal observations. Clin Pediatr (Phila). 16(7):652–656.
    A study was conducted with 59 children, ages 6 to 14 years, heterogeneously grouped together under the diagnosis of the hyperkinetic, minimal brain dysfunction syndrome. Of 32 who were able to tolerate the Feingold salicylate-low and additive-free diet, 11 were markedly improved. A placebo effect could not definitely be ruled out, but the startling changes seen in patients who had been followed for years with other forms of therapy suggest strongly that this improvement was genuine.
  22. Brenner BE, Simon RR. 1982. Management of salicylate intoxication. Drugs. 24(4):335–340.
    Salicylate intoxication is common. It results in impaired generation of adenosine triphosphate and produces a primary respiratory alkalosis. In adults the clinical manifestations may closely simulate a cerebrovascular event or alcoholic ketoacidosis. Central nervous system dysfunction, fever, glycosuria, ketonuria, respiratory alkalosis with an elevated anion gap, tinnitus, dehydration, hypokalaemia and haemostatic defects are common. The diagnosis may be made rapidly by the ferric chloride test or Phenistix test. Standard therapy includes gastric emptying, activated charcoal and alkalinisation of the urine. Osmotic diuresis is a controversial measure. Haemodialysis is indicated for patients with serum salicylate levels more than 100 mg/100ml, severe acid-base disturbance, or deterioration despite optimum therapy.
  23. Brien J-A. 1993. Ototoxicity Associated with Salicylates: A Brief Review. Drug Saf. 9(2):143–148.
    Aspirin, the prototype of the salicylates, is a ubiquitous agent. The availability of aspirin, other salicylates and nonsteroidal anti-inflammatory drugs (NSAIDs) as prescription and over-the-counter medications means there is a wealth of clinical experience with these agents. Among the documented adverse effects of aspirin is the potential for ototoxicity. Tinnitus and hearing loss, usually reversible, are associated with acute intoxication and long term administration of salicylates. A range of measured serum concentrations are reported as correlating with documented ototoxicity (19.6 to >67 mg/dl). Most case reports are based on total serum salicylate concentrations whereas unbound serum salicylate concentrations appear to reflect more closely the risk of ototoxicity. The pathophysiology of toxicity may be related to biochemical and subsequent electrophysiological changes in the inner ear and eighth cranial nerve impulse transmission. Localised drug accumulation and vasoconstriction in auditory microvasculature may be mediated by the antiprostaglandin activity of these agents. Ototoxicity, although not life-threatening, may add to the morbidity of patients taking salicylates or NSAIDs in therapeutic and toxic doses.
  24. Buist RA. 1984. Drug-nutrient interactions—an overview. Int Clin Nutr Rev. 4:114.
  25. Buttriss J. 2008. Dietary intake and bioavailability of plant bioactive compounds. In: Plants: Diet and Health. Oxford, UK: Blackwell Science Ltd. p. 86–106.
    This chapter discusses the current intake, absorption, bioavailability and metabolism of flavonoids (flavonols, flavones, flavan-3-ols and proanthocyanidins), phytoestrogens, carotenoids, hydroxycinnamates, plant sterols, glucosinolates, and hydroxybenzoic acid derivatives. A brief overview of methodologies used in assessing the bioavailability of plant bioactive compounds is also given.
  26. Cabrera C. 2002. Fibromyalgia: A Journey Toward Healing. McGraw-Hill Contemporary.
    Fibromyalgia is one of the fastest-growing diagnoses in the country. Yet, it’s also one of the most controversial diagnoses; many doctors deny its existence, while others use fibromyalgia as a fallback when they are unable to determine the actual cause of ill health. Fibromyalgia: A Journey Toward Healing offers hope and help to the 6 million people who suffer from this condition. With its holistic approach, it shows how patients can achieve lasting wellness and healing through changes in diet and lifestyle and by using herbs. Numerous self-help remedies as well as advice on exercise, physical therapy, and aromatherapy are presented. As Chanchal tells the story of her own struggles with the condition, so she explores practical strategies for healing and being well.
  27. Calnan CD, Cronin E, Rycroft RJ. 1981. Allergy to phenyl salicylate. Contact Dermatitis. 7(4):208–211.
    Six cases of contact dermatitis from a lip salve are described. Five were allergic to phenyl salicylate and one to geraniol in the fragrance. The dermatitis spread in a ring around the mouth. Phenyl salicylate has been removed from the formulation.
  28. Casterline CL. 1975. Intolerance to aspirin. Am Fam Physician. 12(5):119–122.
    The aspirin intolerance syndrome is characterized by rhinitis and/or sinusitis, nasal polyposis and asthma, with or without a history of adverse reactions, following aspirin ingestion. The frequency of this syndrome in a total population of patients with asthma and/or rhinitis has recently been estimated to be 2.4 percent. Aspirin-intolerant individuals can tolerate sodium salicylate and acetaminophen but indomethacin, morphine, codeine and certain pharmaceutical dyes may cause adverse reactions. The mechanism of aspirin intolerance is as yet unclear but does not appear to be on an immunologic basis. Treatment includes strict avoidance of aspirin and symptomatic therapy of rhinitis and asthma.
  29. Cazals Y. 2000. Auditory sensori-neural alterations induced by salicylate. Prog Neurobiol. 62(6):583–631.
    Early after the development of aspirin, almost 150 years ago, its auditory toxicity has been associated with high doses employed in the treatment of chronic inflammatory diseases. Tinnitus, loss of absolute acoustic sensitivity and alterations of perceived sounds are the three auditory alterations described by human subjects after ingestion of large doses of salicylate. They develop over the initials days of treatment but may then level off, fluctuate or decrease, and are reversible within a few days of cessation of treatment. They may also occur within hours of ingestion of an extremely large dose. Individual subjects vary notably as to their susceptibility to salicylate-induced auditory toxicity. Tinnitus may be the first subjective symptom, and is often described as a continuous high pitch sound of mild loudness. The hearing loss is slight to moderate, bilaterally symmetrical and affects all frequencies with often a predominance at the high frequencies. Alterations of perceived sounds include broadening of frequency filtering, alterations in temporal detection, deterioration of speech understanding and hypersensitivity to noise. Behavioral conditioning of animals provides evidence for mild and reversible hearing loss and tinnitus, similar to those observed in humans. Anatomical examinations revealed significant alterations only at outer hair cell lateral membrane. Electrophysiological investigations showed no change in endocochlear resting potential, and small changes in the compound sensory potentials, cochlear microphonic and summating potential, at low acoustic levels. Measures of cochlear mechanical responses to sounds indicated a clear loss of absolute sensitivity and an associated broadening of frequency filtering, both of a magnitude similar to audiometric alterations in humans, but at extremely high salicylate levels. Otoacoustic emissions demonstrated changes in the mechano-sensory functioning of the cochlea in the form of decrease of spontaneous emissions and reduced nonlinearities. In vitro measures of isolated outer hair cells showed reduction of their fast motile responses which are thought to be at the origin of cochlear absolute sensitivity and associated fine filtering. Acoustically evoked neural responses from the eighth nerve to the auditory cortex showed reversible and mild losses of absolute sensitivity and associated broadening of frequency filtering. There is no evidence of a direct alteration of cochlear efferent innervation. Evidence was obtained for decreases in cochlear blood supply under control of autonomous innervation. Spontaneous neural activity of the auditory nerve revealed increases in firings and/or in underlying temporal synchronies. Similar effects were found at the inferior colliculus, mostly at the external nucleus, and at the cortex, mostly at the anterior and less at the secondary auditory cortex but not at the primary auditory cortex. These changes in spontaneous activity might underlie tinnitus as they affect mostly neural elements coding high frequencies, can occur without a loss of sensitivity, are dose dependent, develop progressively, and are reversible. Biochemical cochlear alterations are poorly known. Modifications of oxydative phosphorylation does not seem to occur, involvement of inhibition of prostaglandin synthesis appears controversial but could underlie changes in blood supply. Other biochemical alterations certainly also occur at outer hair cells and at afferent nerve fibers but remain unknown.
  30. Chan TY. 1996. Potential dangers from topical preparations containing methyl salicylate. Hum Exp Toxicol. 15(9):747–750.
    Methyl salicylate (oil of wintergreen) is widely available in many over-the-counter liniments, ointments, lotions or medicated oils for the relief of musculoskeletal aches and pains. Ingestion of methyl salicylate poses the threat of severe, rapid-onset salicylate poisoning because of its liquid, concentrated form and lipid solubility. Excessive usage of these preparations in patients receiving warfarin may result in adverse interactions and bleedings. Methyl salicylate in topical analgesic preparations may cause irritant or allergic contact dermatitis and anaphylactic reactions. Physicians should fully appreciate the potential dangers from topical preparations containing methyl salicylate.
  31. Chen CS, Aberdeen GC. 1980. Potentiation of acoustic-trauma-induced audiogenic seizure susceptibility by salicylates in mice. Experientia. 36(3):330–331.
    Combined exposure to noise and salicylates was found to produce greater acoustic trauma induced audiogenic seizure risk than exposure to the noise alone. The result suggests that salicylates could make the mouse cochlea more vulnerable to the traumatic action of noise.
  32. Chen CS, Aberdeen GC. 1980. Potentiation of noise-induced audiogenic seizure risk by salicylate in mice as a function of salicylate-noise exposure interval. Acta Otolaryngol. 90(1–6):61–65.
    Audiogenic seizure risk can be induced in genetically seizure-resistant BALB/c mice by exposure to an intense noise. Results of this experiment showed that combined exposure to noise and sodium salicylate could produce a greater priming effect than exposure to the noise alone, and the greatest potentiation effect was obtained when animals were exposed to the noise 6 hr after the intake of salicylate. The findings were taken as indirect evidence suggesting that the ototoxic action of sodium salicylate could potentiate vulnerability of the mouse cochlea to noise damage.
  33. Clark JH, Wilson WG. 1981. A 16-day-old breast-fed infant with metabolic acidosis caused by salicylate. Clin Pediatr (Phila). 20(1):53–54.
    This is a report of a 16-day-old, breast-fed infant who presented with metabolic acidosis and no history of drug ingestion. Salicylate intoxication was demonstrated as the probable cause of the acidosis.
  34. Cook PS, Woodhill JM. 1976. The Feingold dietary treatment of the hyperkinetic syndrome. Med J Aust. 2(3):85–8, 90.
    A satisfactory explanation of the hyperkinetic syndrome in children has been lacking. Feingold has advanced the hypothesis that naturally occurring salicylates and artificial food additives may cuase this syndrome in certain children , who have a genetically determined predisposition. Following Feingold's dietary prescription, an elimination diet relevant to the foods available in Sydney was developed. The treatment regime is described, and the results of its application to 15 hyperkinetic children are presented. The parents of 10 children are "quite certain" and those of three others "fairly certain" that their children's behaviour not only improved substantially with the diet, but also relapsed promptly when significant dietary infringements occurred. A possible ecological implication of these findings is briefly discussed.
  35. Cotton EK, Fahlberg. 1964. Hypoglycaemia with salicylate poisoning. A report of two cases. Am J Dis Children. 108:171–3.
    The possible causal association of hypoglycemia in patients with salicylism has recently been emphasized by Mortimer and Lepow.1 They reported four deaths in infants less than 7 months of age in whom the severe hypoglycemia was believed to be related to salicylate ingestion. They also showed that severe hypoglycemia can be produced by feeding salicylates to a starved animal.
    This paper reports two infants who developed severe hypoglycemia apparently secondary to salicylate poisoning; both of the children survived.
  36. Crinnion WJ. 2000. Environmental medicine, part 2-health effects of and protection from ubiquitous airborne solvent exposure. Alternative medicine review: a journal of clinical therapeutic. 5(2):133–143.
    Chemicals known as solvents are part of a broad class of chemicals called volatile organic compounds. These compounds are used in a variety of settings, are ubiquitous, and off-gas readily into the atmosphere. Asa result of their overuse, they can be found in detectable level virtually all samples of both indoor and outdoor air. Certain of these compounds are detectable in adipose samples of all U.S. residents Once in the body they can lead to a variety of neurological, immunological, endocrinological, genitourinary, and hematopoietic problems. Some individuals also have metabolic defects that diminish the liver's clearing capacity for these compounds. Supplementation may be of benefit to help clear these compounds from the body and to prevent adverse health effects.
  37. A Parent's Guide to Diet, ADHD and Behavior.
  38. D’Agati V. 1996. Does aspirin cause acute or chronic renal failure in experimental animals and in humans? Am J Kidney Dis. 28(1):S24–S29.
    There are conflicting reports on the ability of aspirin as a single agent to cause acute or chronic renal failure in experimental animals. Chronic administration of aspirin alone over 18 to 68 weeks in doses of 120 to 500 mg/kg/d has been reported to cause renal papillary necrosis in rats. However, some investigators have been unable to produce renal papillary necrosis in other species or in rats given lower divided doses comparable to therapeutic doses used in humans. In a variety of rat strains, aspirin administered as a single high dose intravenously or by oral gavage produces acute tubular necrosis of proximal tubules, rarely accompanied by renal papillary necrosis in susceptible strains. Several human studies have addressed the chronic nephrotoxicity of aspirin alone or relative risk of end-stage renal disease in association with aspirin use after correction for other analgesics. With the exception of one case control study demonstrating a low, but statistically significant risk of end-stage renal disease in association with aspirin use, all other case control studies and several prospective studies have been unable to identify a significant risk of chronic renal failure in patients using aspirin alone in therapeutic doses. In healthy adults, short-term aspirin administration in therapeutic doses has no effect on creatinine clearance, urine volume, osmolar clearance, or sodium and potassium excretion. However, in predisposed individuals with glomerulonephritis, cirrhosis, and chronic renal insufficiency, and in children with congestive heart failure, short-term aspirin use in therapeutic doses may precipitate reversible acute renal failure. Acute aspirin intoxication (>300 mg/kg) frequently causes acute renal failure and doses of 500 mg/kg may be lethal. Chronic salicylate intoxication has been reported to cause reversible or irreversible acute renal failure in association with a pseudosepsis syndrome.
  39. Dahlén B, Boréus LO, Anderson P, Andersson R, Zetterström O. 1994. Plasma acetylsalicylic acid and salicylic acid levels during aspirin provocation in aspirin-sensitive subjects. Allergy. 49(1):43–49.
    The ability of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) to inhibit the cyclo-oxygenase which catalyzes formation of prostaglandins appears to be central to the mechanisms involved in aspirin sensitivity. We have investigated whether the plasma levels of acetylsalicylic acid (ASA) and its main metabolite salicylic acid (SA) at the time of intolerance reactions correspond with the concentrations required for enzyme inhibition in vitro. Twelve aspirin-sensitive and 15 aspirin-tolerant subjects were followed during provocation with aspirin. ASA and SA concentrations in plasma were determined by HPLC. After oral provocation (up to 460 mg cumulative dose), the levels of ASA and SA in plasma were equivalent in aspirin-sensitive and aspirin-tolerant subjects. For the aspirin-sensitive subjects, at the time of adverse reaction, the concentration range was 2.9-33.3 microM for ASA and 18.1-245 microM for SA. Oral provocation with sodium salicylate yielding 10-fold higher SA levels did not elicit intolerance reactions. Statistically significantly lower levels of ASA and SA (P < or = 0.01) evoked airway obstruction, as compared with merely extrapulmonary symptoms. Bronchial absorption of aspirin was found after inhalation of lysine-aspirin and was comparable in asthmatic and nonasthmatic subjects. In three aspirin-sensitive subjects who developed airway obstruction, the plasma levels for ASA and SA were 0.9-2.6 microM and 0.0-6.7 microM, respectively. In conclusion, the plasma levels of ASA reached at the time of a positive reaction are of the magnitude known to inhibit cyclo-oxygenases. Neither differences in bioavailability of ASA nor the formation of SA seems to contribute to the aspirin-elicited reactions.
  40. Dasgupta A. 2019. Effects of herbal supplements on clinical laboratory test results. In: Accurate Results in the Clinical Laboratory. Elsevier. p. 295–318.
    Herbal supplements are available without prescription in many countries throughout the world and accounting for over $30 billion U.S dollar in sale. A majority of U.S population (25-40%) use herbal supplements while alternative medicines are major forms of therapy in third world countries used by as much as 80% population. Contrary to the popular belief that herbal remedies are safe and effective, many herbal supplements have known toxicity and unexpected laboratory test results may be the early indications of such toxicity. In addition, some herbal products such as St. John’s wort can interact with many Western drugs causing increased clearance of such drugs and hence treatment failure. This monograph would provide information on how herbal supplements affect laboratory test results thus patient’s safety. This monograph would provide a comprehensive and concise practical guide for laboratory professionals, physicians and other health care professionals. The emphasis of this monograph is to provide clinically relevant information rather than discussing in detail mechanisms of such effect, although brief explanations would be provided for such unexpected test results.
  41. de Jong PTVM, Chakravarthy U, Rahu M, Seland J, Soubrane G, Topouzis F, Vingerling JR, Vioque J, Young I, Fletcher AE. 2012. Associations between aspirin use and aging macula disorder: the European Eye Study. Ophthalmology. 119(1):112–118.
    Objective: To study associations between aspirin use and early and late aging macula disorder (AMD). Design: Population-based cross-sectional European Eye Study in 7 centers from northern to southern Europe. Participants: In total, 4691 participants 65 years of age and older, collected by random sampling. Methods: Aspirin intake and possible confounders for AMD were ascertained by a structured questionnaire. Ophthalmic and basic systemic measurements were performed in a standardized way. The study classified AMD according to the modified International Classification System on digitized fundus images at 1 grading center. Nonfasting blood samples were analyzed in a single laboratory. Associations were analyzed by logistic regression. Main outcome measures: Odds ratios (ORs) for AMD in aspirin users. Results: Early AMD was present in 36.4% of the participants and late AMD was present in 3.3% of participants. Monthly aspirin use was reported by 1931 (41.2%), at least once weekly by 7%, and daily use by 17.3%. For daily aspirin users, the ORs, adjusted for potential confounders, showed a steady increase with increasing severity of AMD grades. These were: grade 1, 1.26 (95% confidence interval [CI], 1.08-1.46; P<0.001); grade 2, 1.42 (95% CI, 1.18-1.70), and wet late AMD, 2.22 (95% CI, 1.61-3.05). Conclusions: Frequent aspirin use was associated with early AMD and wet late AMD, and the ORs rose with increasing frequency of consumption. This interesting observation warrants further evaluation of the associations between aspirin use and AMD.
  42. De Swert LFA, Gadisseur R, Sjölander S, Raes M, Leus J, Van Hoeyveld E. 2012. Secondary soy allergy in children with birch pollen allergy may cause both chronic and acute symptoms: Secondary soy allergy: spectrum of symptoms. Pediatr Allergy Immunol. 23(2):117–123.
    Background: Secondary soy allergy occurring in tree pollen allergic patients may cause acute symptoms. Methods: We selected children with birch pollen allergy suspected of also being soy allergic (SA). Soy allergy was proven based on one of the following: (i) a clear-cut clinical history; (ii) a positive provocation test; and (iii) elimination and reintroduction of soy. Skin prick tests (SPT) were performed with a commercial soy extract and with soy flour. Specific IgE to Gly m 4, Gly m 5, and Gly m 6 was determined by means of ImmunoCAP and ISAC. Eight soy-tolerant atopic children being CAP rGly m 4-negative served as a control group for skin testing. Results: Of 15 subjects with birch pollen allergy and being suspected of soy allergy, eight of them proved to be SA; 7/15 subjects proved to be soy tolerant (ST). Besides acute symptoms in 8/8 SA subjects, 3/8 subjects also had been suffering from severe chronic complaints because of soy allergy. SPT with commercial soy extract was negative in all SA and ST subjects tested. SPT with soy flour was positive in 8/8 SA and in 5/6 ST subjects, but negative in all 8 controls (p < 0.0001); the median weal diameter was 7.7 mm in SA subjects, compared to 3 mm in ST subjects (p < 0.01). The median IgE level to rGly m 4 using CAP and ISAC was, respectively, 32.4 kU/l and 4.0 ISU in SA subjects, compared to 6.2 kU/l and 0.4 ISU in ST subjects (p < 0.05). Analysis of IgE to nGly m 5 and nGly m 6, using CAP or ISAC, showed no significant differences between SA and ST subjects. Conclusions: Secondary soy allergy may cause severe chronic besides acute symptoms. SPT with soy flour is a sensitive and specific tool in detecting soy sensitization. SPT with soy flour, CAP rGly m 4, and ISAC rGLY m 4 are valuable tools in the diagnosis of birch-pollen-associated secondary soy allergy.
  43. DeBartolo HM Jr. 1989. Zinc and diet for tinnitus. Am J Otol. 10(3):256.
    Management of cellular microenvironment by dietary alteration provides a complex, highly sophisticated, physiologic and biochemical approach to tinnitus.
  44. Dellinger TM, Livingston HM. 1998. Aspirin burn of the oral cavity. Ann Pharmacother. 32(10):1107.
  45. Pastor PN, Reuben CA. 2008. Diagnosed attention deficit hyperactivity disorder and learning disability: United States, 2004-2006. Vital Health Stat 10.(237):1–14.
    Objectives: This report presents national estimates of the prevalence of diagnosed attention deficit hyperactivity disorder (ADHD) and learning disability (LD) in U.S. children 6-17 years of age and describes the prevalence of these conditions for children with selected characteristics. The use of educational and health care services and the prevalence of other health conditions are contrasted for children with ADHD without LD, LD without ADHD, both conditions, and neither condition. Methods: Estimates are based on data from the National Health Interview Survey (NHIS), an ongoing national household survey of the civilian noninstitutionalized population of the United States. The analysis focuses on 23,051 children 6-17 years of age in the child sample of the 2004, 2005, and 2006 NHIS. Results: About 5% of children had ADHD without LD, 5% had LD without ADHD, and 4% had both conditions. Boys were more likely than girls to have each of the diagnoses (ADHD without LD, LD without ADHD, and both conditions). Children 12-17 years of age were more likely than children 6-11 years of age to have each of the diagnoses. Hispanic children were less likely than non-Hispanic white and non-Hispanic black children to have ADHD (with and without LD). Children with Medicaid coverage were more likely than uninsured children and privately insured children to have each of the diagnoses. Children with each of the diagnoses were more likely than children with neither ADHD nor LD to have other health conditions. Children with ADHD were more likely than children without ADHD to have contact with a mental health professional, use prescription medication, and have frequent health care visits. Children with LD were more likely than children without LD to use special education services.
  46. Doeglas HM. 1975b. Reactions to aspirin and food additives in patients with chronic urticaria, including the physical urticarias. Br J Dermatol. 93(2):135–144.
    In 131 patients with chronic urticaria, including physical urticarias, oral provocation tests were done with aspirin. A total of thirty-one patients showed a reaction on aspirin challenge. Reactions were seen in 35% of patients with idiopathic urticaria, 52% of patients with cholinergic urticaria, and 43% of those with pressure urticaria. The patients with reactions to aspirin were also tested with tartrazine, sodium benzoate, 4-hydroxy benzoic acid, sodium- and phenyl salicylate and the analgesics indomethacin, paracetamol and mefenamic acid. In nineteen of twenty three aspirin sensitive patients, positive reactions to one or more of these substances were observed. Indomethacin and tartrazine had the highest scores. There was no statistically significant correlation between aspirin reactions and the presence of nasal polyposis, sinusitis, asthma or atopy.
  47. Dooley CP, Mello WD, Valenzuela JE. 1985. Effects of aspirin and prostaglandin E2 on interdigestive motility complex and duodenogastric reflux in man. Dig Dis Sci. 30(6):513–521.
    Both increased duodenogastric reflux and chronic aspirin ingestion are associated with the development of gastric ulcers in man. Animal studies suggest aspirin increases duodenogastric reflux. Prostaglandin E2 protects gastric mucosa from the effects of many injurious agents and inhibits gastric motility, but its effect on duodenogastric reflux is unknown. We have studied the effects of aspirin and a synthetic derivative of prostaglandin E2 on duodenogastric reflux during fasting in six normal subjects, while concomitantly monitoring gastrointestinal motility by means of a perfused catheter system. We found that duodenogastric reflux (as measured by bile salt output in gastric aspirates) increased significantly (P less than 0.05) following both the prostaglandin E2 derivative and aspirin. This increase occurred in phases II and III of the interdigestive motility complex. Both drugs were associated with a significant reduction (P less than 0.05) in frequency and amplitude of antral contraction during phase II. Both drugs also induced a significant disruption (P less than 0.01) of phase III, increasing the number of complexes without an antral and duodenal component. These effects of aspirin may be one of the factors predisposing to the gastric mucosal damage associated with aspirin. The prostaglandin E2 derivative protects gastric mucosa by mechanisms other than reducing duodenogastric reflux and ameliorating the motility disturbances caused by aspirin.
  48. Santos MA, Ce SG, F MC. 2001. Menthol-induced asthma: a case report. J Investig Allergol Clin Immunol. 11(1).
    A case of asthma due to menthol is reported in a 40-year-old woman with no history of asthma or any other allergy. During the last two years, the patient had presented dyspnea, wheezing and nasal symptoms when exposed to mentholated products such as toothpaste and candies. The etiology was suggested by the history of exposure and diagnosis was established by skin tests and bronchial challenge with menthol. The patient achieved control of symptoms by avoiding menthol and its derivatives.
  49. Drummond R, Kadri N, St-Cyr J. 2001. Delayed salicylate toxicity following enteric-coated acetylsalicylic acid overdose: a case report and review of the literature. CJEM. 3(01):44–46.
    Salicylates are widely available and potentially lethal. Clinical and laboratory findings associated with enteric-coated acetylsalicylic acid (ECASA) ingestion may be delayed more than 24 hours. When dealing with patients who have a history of significant ingestion, emergency physicians should consider initiating therapy regardless of initial salicylate levels. Prolonged observation may be necessary in cases of suspected ECASA overdose.
  50. Duckwall EW. 1905. Canning and Preserving of Food Products with Bacteriological Technique: A Practical and Scientific Hand Book for Manufacturers of Food Products, Bacteriologists, Chemists, and Students of Food Problems. Vol. 1.
  51. Duggin GG. 1996. Combination analgesic-induced kidney disease: The australian experience. Am J Kidney Dis. 28(1):S39–S47.
    Analgesic nephropathy is a unique drug-induced kidney disease characterized pathologically by renal papillary necrosis and chronic interstitial nephritis, and is the result of excessive consumption of combination antipyretic analgesics. The clinical features of the disorder relate mainly to the papillary necrosis, renal colic, and obstructive uropathy and the development of chronic renal failure in a small percentage of patients. There are significant geographic variations in the clinical features that may be related to the differing combinations of analgesics. The pathogenesis of the disease is in part related to the kidneys' ability to concentrate drugs in the papillae. The following sequence of events presents a plausible explanation for the evolution of the disease. If a combination of phenacetin and aspirin is ingested, the following steps occur. Phenacetin is converted in the gut and liver to acetaminophen by first-pass metabolism. Acetaminophen is then taken up by the kidney and excreted. During its excretion, acetaminophen becomes concentrated in the papillae of the kidney during physiologic degrees of antidiuresis, the concentration being up to five times the intracellular concentration of other tissues. Acetaminophen undergoes oxidative metabolism by prostaglandin H synthase to a reactive quinoneimine that is conjugated to glutathione. If acetaminophen is present alone, there is sufficient glutathione generated in the papillae to detoxify the reactive intermediate. If the acetaminophen is ingested with aspirin, the aspirin is converted to salicylate and salicylate becomes highly concentrated in both the cortex and papillae of the kidney. Salicylate is a potent depletor of glutathione. The mechanism is not completely understood; however, the inhibition of the production of NADPH via the pentose shunt is a possible explanation. With the cellular glutathione depleted, the reactive metabolite of acetaminophen then produces lipid peroxides and arylation of tissue proteins, ultimately resulting in necrosis of the papillae.
  52. Duke JA. 2017. Handbook of phytochemical constituents of GRAS herbs and other economic plants. In: Handbook of Phytochemical Constituents of GRAS Herbs and Other Economic Plants. Routledge. p. 1–654.
    CRC Handbook of Phytochemical Constituents of GRAS Herbs and Other Economic Plants is a unique catalog that includes more than 15,000 phytochemical constituents from over 1,000 higher plant species. This volume covers all of the generally-recognized-as-safe (GRAS) herbs and at least 250 important food and medicinal plants. Each entry features the scientific name, one or more common names, a listing of phytochemical constituents, a single datum or range of quantitative data (wet-weight to dry-weight in parts per million), two-letter abbreviation identifying the plant part, and three-letter abbreviation(s) indicating the source(s) of the data. The extraordinary amount of data compiled into an easy-to-use tabular format makes the CRC Handbook of Phytochemical Constituents of GRAS Herbs and Other Economic Plants a volume useful to all pharmacologists, toxicologists, nutritionists, pharmacognicists, and food scientists.
  53. Duthie GG, Wood AD. 2011. Natural salicylates: foods, functions and disease prevention. Food Funct. 2(9):515–520.
    Salicylic acid and related compounds are produced by plants as part of their defence systems against pathogen attack and environmental stress. First identified in myrtle and willow, the medical use of salicylate-rich preparations as anti-inflammatory and antipyretic treatments may date back to the third millennium BC. It is now known that salicylates are widely distributed throughout the plant kingdom, and they are therefore present in plant products of dietary relevance. In the UK, major food sources are tomato-based sauces, fruit and fruit juice, tea, wine, and herbs and spices. In mammalian cells, salicylic acid demonstrates several bioactivities that are potentially disease-preventative, including the inhibition of production of potentially neoplastic prostaglandins, which arise from the COX-2 mediated catalysis of arachidonic acid. Moreover, it appears to be readily absorbed from the food matrix. This has led some to suggestions that the recognised effects of consuming fruit and vegetables on lowering the risk of several diseases may be due, in part, to salicylates in plant-based foods. However, published estimates of daily salicylic acid intake vary markedly, ranging from 0.4 to 200 mg day(-1), so it is unclear whether the Western diet can provide sufficient salicylates to exert a disease-preventative activity. Some ethnic cuisines that are associated with lowered disease risk may contain considerably more salicylic acid than is obtainable from a Western diet. However known protective effects of acetylsalicylic acid (Aspirin™) may have lead to an over-emphasis on the importance of dietary salicylates compared with other bioactive plant phenolics in the diet.
  54. Dykes L, Rooney LW. 2007. Phenolic compounds in cereal grains and their health benefits. Cereal foods world. 52(3):105-111.
  55. American Academy of Pediatrics. 2008. ADHD and food additives revisited. AAP Grand Rounds. 19(2):17-17.
  56. Elverland HH. 1996. Sensitivity to acetylsalicylic acid. Tidsskrift for den Norske laegeforening: tidsskrift for praktisk medicin, ny raekke. 116(6):754–756.
    Because of its ability of prevent platelet aggregation, the use of aspirin in Norway is rising abruptly, after some years of fairly low consumption. The author reviews of aspirin-sensitivity, including chronic rhinosinusitis, nasal polyposis and corticosteroid-dependent asthma. Non-steroidal anti-inflammatory drugs have widespread cross-reactions with aspirin, while azo-dyes and food preservatives may induce a similar chronic inflammation of the airways. Why some people develop aspirin-sensitivity is unknown. The basic biochemical mechanisms of aspirin-sensitivity are discussed. Specific treatment based on desensitisation and development of leukotriene receptor antagonists may be rewarding in the future. Possible beneficial or adverse effects of life-long, low-dose use of aspirin on aspirin-sensitivity should be monitored.
  57. Eriksson NE. 1978. Food Sensitivity Reported by Patients with Asthma and Hay Fever: A Relationship between Food Sensitivity and Birch Pollen‐Allergy and between Food Sensitivity and Acetylsalicylic Acid Intolerance. Allergy. 33(4):189–196.
    Among adult patients with bronchial asthma and/or allergic rhinitis und allergological investigation with skin test, nasal provocation test and RAST, 1129 answered a questionaire regarding food sensitivity (FS). 276 (24%) of the patients reported some kind of allergic symptoms on eating or handling various foods, of which hazel nut, apple and shell fish were the most often mined. Females reported FS most often than males, A correlation was found between birch pollen allergy and FS with nuts, apple, peach, cherry, pear, plum, carrot and new potato. The higher the degree of birch pollen allergy, according to skin test. RAST or provocation test, the higher the frequency of FS. A correlation was found too between acetylsalicylic acid intolerance and FS with some foods, e.g. nuts, strawberry, almond, green pepper, hip, chocolate, egg, cabbage, milk and wine. The connection between birch pollen allergy and FS is probably explained by the structural relationship between birth pollen allergen and some allergens of die foodstuffs, whereas the high incidence of FS in acetylsalicylic acid-intolerant patients is probably explained by additives in foods as well as salicylates or benzoates naturally occurring in some food.
  58. Feingold B, Feingold H. 1979. The Feingold Cookbook for Hyperactive Children and others with problems associated with food additives and salicylates. Random House.
    Dietary management of hyperkinetic and learning-disabled children has led to lessened family and peer conflict and increased scholastic performance withoutneed for medication. Hyperactive children demonstrate symptoms of sleeplessness, hyperactive behavior, aggressiveness, destructiveness, abusiveness, short attention span, and inability to concentrate for more than a few moments. When the differentiation between childhood exuberance and hyperactivity is difficult to distinguish, the diet can be tried for a period and behavioral changes noted. The Feingold diet eliminates two groups of foods: 1. synthetic (artificial) colors and flavors and two preservatives - BHT and BHA; 2. fruits and vegetables, and miscellaneous that contain natural salicylates. Stages in diet management: 1. eliminating the two groups of foods and keeping a diary of food intake, medication, a nd behavioral changes; 2. after 4-6 weeks of good response, introduce salicylate fruits and vegetables (but never foods from the first group). Effects of sugarand vitamins, parent hints, and other conditions that may respond to the diet are discussed.
  59. Feingold BF. 1979. Dietary management of nystagmus. J Neural Transm. 45(2):107–115.
    Two case reports illustrate the therapeutic response of congenital nystagmus to a diet eliminating synthetic food colors, synthetic food flavors, the antioxidant preservatives butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA), and a small group of foods thought to contain a natural salicylate radical.
    A brief discussion of the hyperkinetic syndrome is offered with the proposal that a variety of neurologic and neuromuscular disturbances (grand mal, petit mal, psychomotor seizures; La Tourette syndrome; autism; retardation; the behavioral component of Down's syndrome; and oculomotor disturbances) may be induced by identical chemicals, depending upon the individual's genetic profile and the interaction with other environmental factors. It is perhaps the failure to integrate all the signs presented by the various clinical patterns with hyperkinesis or Minimal Brain Dysfunction (MBD) under a single heading that eye muscle involvement manifested as either nystagmus or strabismus has not been emphasized as part of the hyperkinetic syndrome.
  60. Fimiani M, Casini L, Bocci S. 1990. Contact dermatitis from phenyl salicylate in a galenic cream. Contact Dermatitis. 22(4):239.
    The patient's topical medicaments, showed positive reactions only to balsam of Peru and paraben-mix at 48 and 72 h ( + / + + ). Further patch tests with the individual constituents of paraben-mix showed positive reactions to methyl and ethyl parabens. While parabens were not present in the topical medicaments used by our patient, they were present in the systemically administered ampicillin (methyl and propyl para-hydroxy-benzoate at a concentration of 18 mg/g).
  61. Fisherman EW, Cohen GN. 1973. Aspirin and other cross-reacting small chemicals in known aspirin intolerant patients. Ann Allergy. 31(10):476–484.
  62. Fitzsimon M, Holborow P, Berry P, Latham S. 1978. Salicylate sensitivity in children reported to respond to salicylate exclusion. Med J Aust. 2(12):570–572.
    Twelve children, aged six to 13 years, whose parents reported an improvement in behavioural problems with use of the Feingold (K-P) diet for an average period of 12 months, were challengetested with 40 mg of acetylsalicylic acid in a double-blind, cross-over trial with ascorbic acid as a placebo. The children were tested within three hours of ingestion of either the experimental or placebo tablet with a battery of psychological and neurological tests, and were rated by a parent on an enlarged Conners' Parent-Teacher Questionnaire for four days after the ingestion of the tablet. It was found that significance was reached in tests of general cognitive capacity, line walking and the “finger-to-nose” tests, as well as increased disturbance in sleep patterns in these children.
  63. Flarup M, Udholm S. 1989. Tardive anaphylactic shock caused by intolerance to aspirin. Ugeskr Laeger. 151(35):2211–2212.
    A case of tardive anaphylactic shock resulting from intolerance of acetyl salicylic acid is presented. The precipitating mechanism of ASA-intolerance is complex and not yet fully elucidated but possibly involves anaphylate toxins activated by mast cells. The symptoms may occur immediately or after a prolonged latent period and are dependent on the dosage. Patients with asthma and chronic urticaria/angiooedema show increased prevalence of ASA-intolerance and these patients should be advised to be careful with ASA/NSAID preparations.
  64. García Rodríguez LA, Lin KJ, Hernández-Díaz S, Johansson S. 2011. Risk of upper gastrointestinal bleeding with low-dose acetylsalicylic acid alone and in combination with clopidogrel and other medications. Circulation. 123(10):1108–1115.
    Background— This study evaluated the risk of upper gastrointestinal bleeding (UGIB) associated with use of low-dose acetylsalicylic acid (ASA) alone and in combination with other gastrotoxic medications. Methods and Results— The Health Improvement Network UK primary care database was used to identify individuals 40 to 84 years of age with a UGIB diagnosis in 2000 to 2007 (n=2049). An age-, sex-, and calendar year-matched control group (n=20 000) was identified from the same source population. The relative risk (RR) of UGIB associated with use of low-dose ASA (75 to 300 mg/d), clopidogrel, and other commonly coadministered medications was estimated by multivariate logistic regression. The risk of UGIB was increased in current users of low-dose ASA (RR, 1.80; 95% confidence interval [CI], 1.59 to 2.03) or clopidogrel (RR, 1.67; 95% CI, 1.24 to 2.24) compared with nonusers. Compared with low-dose ASA monotherapy, the risk of UGIB was significantly increased when low-dose ASA was coadministered with clopidogrel (RR, 2.08; 95% CI, 1.34 to 3.21), oral anticoagulants (RR, 2.00; 95% CI, 1.15 to 3.45), low-/medium-dose nonsteroidal antiinflammatory drugs (RR, 2.63; 95% CI, 1.93 to 3.60), high-dose nonsteroidal antiinflammatory drugs (RR, 2.66; 95% CI, 1.88 to 3.76), or high-dose oral corticosteroids (RR, 4.43; 95% CI, 2.10 to 9.34); this was not apparent with coadministration of statins (RR, 0.99; 95% CI, 0.81 to 1.21) or low-dose oral corticosteroids (RR, 1.01; 95% CI, 0.58 to 1.77). Conclusions—Use of low-dose ASA is associated with an almost 2-fold increase in the risk of UGIB compared with nonuse. This risk is increased further in individuals taking low-dose ASA along with clopidogrel, oral anticoagulants, nonsteroidal antiinflammatory drugs, or high-dose oral corticosteroids.
  65. Genton C, Frei PC, Pécoud A. 1985. Value of oral provocation tests to aspirin and food additives in the routine investigation of asthma and chronic urticaria. J Allergy Clin Immunol. 76(1):40–45.
    Nonsteroidal anti-inflammatory drugs and certain food or drug additives are known to induce acute bronchospasms, angioneurotic edema, and urticaria in susceptible patients. Thirty-four patients (17 with asthma and 17 with urticaria), whose case history suggested such intolerance, were challenged orally with increasing doses of seven compounds: acetylsalicylic acid, glafenine, sodium benzoate, sulfur dioxide, potassium sorbate, sodium glutamate, and tartrazine. Among 162 oral provocation tests, 38 were positive (20% decrease in peak flow rate or appearance of acute urticaria/angioneurotic edema). Twenty-four of the 34 patients (nine with asthma and 15 with urticaria) were intolerant to at least one compound. However, no serious reaction was observed. In 20 of these 24 patients (six with asthma and 14 with urticaria), a diet free of additives and nonsteroidal anti-inflammatory drugs resulted, within 5 days, in a marked improvement of symptoms, which persisted 8 to 14 mo after starting the diet. Age, prevalence of IgE-mediated allergy, and nasal polyposis were similar in patients with or without reactions of intolerance. Under the conditions used, oral provocation tests proved to be feasible, safe, and useful in many patients not helped by existing methods.
  66. Germann R, Schindera I, Kuch M, Seitz U, Altmeyer S, Schindera F. 1996. Life threatening salicylate poisoning caused by percutaneous absorption in severe ichthyosis vulgaris. Hautarzt. 47(8):624–627.
    In a 7-year-old boy, ichthyosis vulgaris was treated with a 10% ointment for application over a large area of the body surface. In this way, the child received 400 g salicylic acid (0.6 g/kg body weight per day) percutaneously over a period of 4 weeks. The patient was referred to hospital by the family doctor: he was in a deep somnolent state, apparently caused by hyperventilation following wheezing, vomiting, tinnitus and vertigo. Salicylate intoxication was suspected because of metabolic acidosis, an anion gap and respiratory overcompensation. The diagnosis was confirmed by a serum salicylate level of 985 micrograms/ml (therapeutic level 150-300 micrograms/ml). Following forced diuresis and alkalization with sodium bicarbonate, haemodialysis was unnecessary. As the salicylate level declined to values within the therapeutic range, the patient started to recover consciousness, waking on the 4th day. By day 6 there were still obvious neurological deficiencies. Fecal incontinence, bilateral ptosis and intermittent diverging strabismus on the right persisted for some weeks. It was 6 months before complete neurological resolution was achieved. The pathogenesis of salicylate toxicity and the need for safer therapies for ichthyosis vulgaris are discussed.
  67. Duthie GG, Wood AD. 2011. Natural salicylates: foods, functions and disease prevention. Food Funct. 2(9):515–520.
    Salicylic acid and related compounds are produced by plants as part of their defence systems against pathogen attack and environmental stress. First identified in myrtle and willow, the medical use of salicylate-rich preparations as anti-inflammatory and antipyretic treatments may date back to the third millennium BC. It is now known that salicylates are widely distributed throughout the plant kingdom, and they are therefore present in plant products of dietary relevance. In the UK, major food sources are tomato-based sauces, fruit and fruit juice, tea, wine, and herbs and spices. In mammalian cells, salicylic acid demonstrates several bioactivities that are potentially disease-preventative, including the inhibition of production of potentially neoplastic prostaglandins, which arise from the COX-2 mediated catalysis of arachidonic acid. Moreover, it appears to be readily absorbed from the food matrix. This has led some to suggestions that the recognised effects of consuming fruit and vegetables on lowering the risk of several diseases may be due, in part, to salicylates in plant-based foods. However, published estimates of daily salicylic acid intake vary markedly, ranging from 0.4 to 200 mg day−1, so it is unclear whether the Western diet can provide sufficient salicylates to exert a disease-preventative activity. Some ethnic cuisines that are associated with lowered disease risk may contain considerably more salicylic acid than is obtainable from a Western diet. However known protective effects of acetylsalicylic acid (Aspirin™) may have lead to an over-emphasis on the importance of dietary salicylates compared with other bioactive plant phenolics in the diet.
  68. Ghislain PD, Ghislain E. 2000. Aspirin-induced angioedema of the nape of the neck with naproxen cross-reaction: a case report. Annales de medecine interne. 151(3):227–229.
    We report a case of angioedema limited to the nape of the neck. The symptoms occurred every morning for fifteen days, two or three hours after taking aspirin. The patient took salicylic acid, 100mg per day, orally for two years. The angioedema occurred alone, without urticaria. When aspirin was stopped, the symptoms disappeared. A few weeks later, the patient took napoxen, with occurrence of more pronounced symptoms. The causality score was I3 for both drugs. The most common side-effects of aspirin intake are asthma and urticaria/angioedema. The mechanism of this hypersensitivity is unknown. There are numerous cross-reactions between aspirin and other NSAIDs. This case points out the importance of accurate history taking concerning self-medication for the diagnosis of angioedema.
  69. Gibson A, Clancy R. 1980. Management of chronic idiopathic urticaria by the identification and exclusion of dietary factors. Clin Exp Allergy. 10(6):699–704.
    The role played by dietary chemical factors in the pathogenesis of chronic idiopathic urticaria (CIU) was assessed in seventy-six patients by challenge. Stable remission was first established by using an empirically established ‘exclusion diet’. A diet modified to exclude those chemicals giving a positive response to challenge was demonstrated to be of therapeutic value for time periods of up to 18 months. Re-testing twelve patients at 12 months indicated that most patients positive to salicylate or benzoate challenge retained this pattern of reactivity.
  70. Gogoll L, Bentsen P, Hochrein H. 1989. Cerebral complications in chronic acetylsalicylic acid poisoning. Deutsche medizinische Wochenschrift. 114(5):177–180.
    A 60-year-old woman who for many years had been taking salicylate-containing tablets for headaches, was admitted to hospital, in a somnolent state, because of increasing weakness, tiredness, memory and speech disorders, and tinnitus. Laboratory tests revealed a decompensated metabolic acidosis (pH 7.25), renal insufficiency (creatinine 2.3 mg/dl) and a decreased Quick value (63%). Whole-blood acetylsalicylic acid concentration was markedly elevated to 330 micrograms/ml. After treatment of the acidosis with bicarbonate and forced diuresis she at first regained consciousness, but clouding of consciousness again occurred eight hours later progressing to coma with unequal pupils and seizure potentials in the electroencephalogram. Status epilepticus without motor component was diagnosed, perhaps the result of a dysequilibrium of acid-base balance between blood and cerebrospinal fluid. The signs and symptoms were quickly reversed under treatment with clonazepam.
  71. Gosepath J, Hoffmann F, Schäfer D, Amedee RG, Mann WJ. 1999. Aspirin intolerance in patients with chronic sinusitis. ORL J Otorhinolaryngol Relat Spec. 61(3):146–150.
    Aspirin intolerance in patients with chronic sinusitis is often a cause of early recurrence of symptoms after surgical treatment. This study assesses 84 patients who were tested for acetylsalicylic acid intolerance after presenting with symptoms like chronic rhinosinusitis, sometimes bronchial asthma, coexisting allergies or a history of aspirin sensitivity. Nasal polyposis was found in a majority of cases, often recurrent after previous surgery. The levels of eicosanoids such as peptido-leukotrienes and prostaglandin E2 were analyzed in isolated blood cells and compared with a healthy control group. Aspirin-intolerant patients showed elevated basal levels of peptido-leukotrienes and reduced basal levels of prostaglandin E2. Test results were graded in a system ranging from positive (68%), signifying aspirin intolerance, to borderline (18%) and negative results (14%). After screening patients with clinical findings indicating a possible aspirin intolerance, the results of this investigation reveal a strong correlation between the clinical symptomatology and the in vitro parameters of eicosanoid levels in isolated blood cells, indicating the need to induce aspirin tolerance to reduce the risk of recurrent rhinosinusitis.
  72. Grzelewska-Rzymovska I, Bogucki A, Szmidt M. 1985. Migraine in aspirin-sensitive asthmatics. Allergol Immunopathol. 13:13–16.
    The aim of this study was to evaluate the occurrence of migraine in aspirin-sensitive asthmatics, and was performed in 46 aspirin-sensitive asthmatic patients (ASA). The control group consisted of 46 asthmatics without aspirin sensitivity. In all patients allergological and laryngological examinations were performed and histories concerning the occurrence of migraine were collected. Twenty one (45.7%) of aspirin-sensitive asthmatic patients suffered from migraine, 5 from classical migraine and 1 from dietary migraine. In the control group migraine was found in only 6 (13%) persons. A family history of migraine was positive in 11 (52.4%) asthmatics with aspirin-sensitivity and migraine and in only 1 (17%) patient with migraine but without aspirin-sensitivity. The authors conclude that the high incidence of migraine in aspirin-sensitive asthmatics may be related to a defect in their arachidonic acid metabolism.
  73. Halla JT, Hardin JG. 1988. Salicylate ototoxicity in patients with rheumatoid arthritis: a controlled study. Ann Rheum Dis. 47(2):134–137.
    Tinnitus or subjective hearing loss, or both, were reported by 61 of 134 (45%) patients with rheumatoid arthritis (RA) taking regular salicylates and by 73 of 182 (40%) untreated healthy subjects. In the patients with RA mean salicylate levels were not higher in those with tinnitus than in those without tinnitus, but levels were significantly higher in those with subjective hearing loss than in those with no symptoms. Twenty five per cent of the patients with RA had tinnitus or subjective hearing loss with salicylate levels less than 1.42 mmol/l. Audiometric responses in 31 patients correlated poorly with symptoms. Tinnitus and subjective hearing loss may be too non-specific to be reliable as tools for adjusting the salicylate level into the therapeutic range.
  74. Johnson CC, Hanzlik PJ. 1929. THE SALICYLATES XVIII. ACTIONS OF AMMONIUM SALICYLATE COMPARED WITH SODIUM SALICYLATE. Journal of Pharmacology and Experimental Therapeutics. 36(3):319–333.
  75. Hartwig-Otto H. 1983. Pharmacokinetic considerations of common analgesics and antipyretics. Am J Med. 75(5):30–37.
    Knowledge of pharmacokinetics (action of organisms on drugs) and pharmacodynamics (drug action on living organisms) allows for the proper assessment of the most suitable dose, dosing intervals, route of administration, as well as dose adjustment when clinically indicated. The basic physical scientific principles of the movement of drug particles across biologic barriers, their subsequent conversion to other chemical forms, and their elimination are reviewed in general terms. The specific metabolic pathways for aspirin and paracetamol (acetaminophen) are then discussed in more detail. Elimination of salicylate involves two saturable (nonlinear) major pathways and three apparently first-order (linear) minor pathways; these mixed order kinetics lead to somewhat complex mathematics affecting elimination half-life which, in turn, can have implications for anticipating side effects and toxicity. The kinetics of acetaminophen also involve various pathways, but studies have shown a good correlation between the expected and the observed elimination half-life of this drug. Comparison is made between the in vivo handling of the two analgesics, but it is stressed that these data apply only to healthy adults under normal conditions and cannot be extrapolated to patients with underlying disease processes.
  76. Hausen BM, Schulz KH. 1984. Allergy to dyes in stockings. Dtsch Med Wochenschr. 109(39):1469–1475.
    Skin allergies caused by the wearing of stockings and hose have received little attention. Findings in patients of an allergy department, enquiries at stocking counters of stores and recent publications indicate, however, that probably many more persons have an allergy to stocking dyes than is generally thought. Skin tests with isolated stocking dyes indicate that azo dye dispersion yellow 3, dispersion orange 3 and dispersion red 1 are the most important contact allergens. They were demonstrated in 18-21 of the 23 hose examined. In textile materials, azo dye dispersion blue 124 is predominant among allergens. Cross-reactions may occur to other dispersion azo dyes, used in cosmetics, textiles, toiletries and hygenic articles, permitted food additives and hair dyes. It is suggested that in persons who have dye allergy or intolerance, decolouration followed by colouring with natural colours be undertaken.
  77. Healy E, Newell L, Howarth P, Friedmann PS. 2008. Control of salicylate intolerance with fish oils. Br J Dermatol. 159(6):1368–1369.
    We report three patients with disabling salicylate-induced intolerance who experienced abrogation of symptoms following dietary supplementation with ω-3 polyunsaturated fatty acids (PUFAs). All three patients experienced severe urticaria, asthma requiring systemic steroid therapy and anaphylactic reactions. After dietary supplementation with 10 g daily of fish oils rich in ω-3 PUFAs for 6–8 weeks all three experienced complete or virtually complete resolution of symptoms allowing discontinuation of systemic corticosteroid therapy. Symptoms relapsed after dose reduction. Fish oil appears a safe and effective treatment for this difficult and often serious condition.
  78. Hertz-Picciotto I. 1993. Effects of aspirin on female reproductive function and on in utero development. Boca Raton (FL: CRC Press). 73–88.
    Series abstract: Recently, aspirin has been found to be associated with a decreased risk of heart disease and other newly found health benefits. However, it produces allergy-like and toxic effects in many individuals. Beneficial and Toxic Effects of Aspirin reviews in a single volume the benefits of aspirin and its adverse effects. A panel of experts has been gathered to contribute to this work, providing a balanced view of multiple topics. Contributors to this volume include outstanding allergists who describe bronchial and skin sensitivity to aspirin as well as prevention and treatment.
  79. Higgs GA, Salmon JA. Is aspirin a pro-drug for salicylate? In: Aspirin and Other Salicylates. Ed Vane JR, Botting RM. Chapman and Hall 1992, 63-73.
  80. Holmes G, Freeman S. 2001. Cheilitis caused by contact urticaria to mint flavoured toothpaste. Australas J Dermatol. 42(1):43–45.
    A 26-year-old woman presented with a 12-month history of persistent dermatitis of the lips. She had failed to respond to cosmetic avoidance and therapeutic measures. Patch testing was negative, including her toothpaste and toothpaste flavours. She defied diagnosis until an acute flare followed immediately after dental treatment with a mint flavoured tooth cleaning powder. This led us to prick test her to mint leaves and this was positive. Her cheilitis settled after changing from her mint-flavoured toothpaste. A diagnosis of contact urticaria should be considered in cases of cheilitis of unknown cause.
  81. Howrie DL, Moriarty R, Breit R. 1985. Candy flavoring as a source of salicylate poisoning. Pediatrics. 75(5):869–871.
    Methyl salicylate (oil of wintergreen) in the form of candy flavoring was ingested by a 21-month-old male infant who subsequently developed vomiting, lethargy, and hyperpnea. A "swallow" of the solution resulted in a serum salicylate concentration of 81 mg/dL six hours after ingestion. The infant was treated with parenteral fluids and sodium bicarbonate and he recovered rapidly. Hazards associated with salicylate use in this form include lack of parental awareness of the substance's toxic potential, the attractiveness of the candy-like odor, and the availability of the liquid in non-child-resistant packaging containing potentially lethal quantities.
  82. Inoue F, Walsh RJ. 1983. Folate supplements and phenytoin‐sa] licylate interaction. Neurology. 33(1):115–115.
    We found biphasic fluctuations of serum phenytoin level when aspirin was added to chronic phenytoin therapy for an epileptic patient. The total serum phenytoin level was lowered initially by addition of aspirin. However, after 4 months on phenytoin-aspirin combination therapy, he showed elevated serum phenytoin levels, mild nystagmus, and serum folate deficiency.
  83. Isaacs KL, Murphy D. 1990. Pancreatitis after rectal administration of 5-aminosalicylic acid. J Clin Gastroenterol. 12(2):198–199.
    A patient treated with sulfasalazine for new-onset ulcerative colitis developed self-limited pancreatitis. Rechallenge with 5-aminosalicylic acid (5-ASA) in enema form (Rowasa) again induced pancreatitis. Recent case reports suggest that the salicylate component of sulfasalazine can lead to the development of pancreatitis with oral 5-ASA administration. This patient's course demonstrates further that rechallenge with 5-ASA in a rectal form may also lead to pancreatitis.
  84. Jacobson MF, Schardt D. 1999. Diet, ADHD & Behavior: A Quarter-Century Review [and] A Parent’s Guide to Diet. ADHD & Behavior.
    This report reviews 23 controlled studies of the effect of food dyes and other dietary constituents on the behavior of children with Attention-Deficit/Hyperactivity Disorder (ADHD) or other behavioral problems. Findings indicate 17 of the 23 studies found evidence that some children's behavior significantly worsens after they consume artificial colors or certain foods such as milk or wheat. Limited research with such tools as electroencephalography indicates that certain foods trigger physiological changes in sensitive individuals. The report includes the following recommendations: (1) the government, private agencies, and health practitioners should acknowledge the potential for diet to affect behavior and advise parents to consider diet modification; (2) parents should consider dietary changes (along with behavioral therapy) as the first course of treatment for children with behavioral problems; (3) the National Institutes of Health should sponsor research to determine which foods and food additives affect behavior, develop methods of identifying sensitive children, and sponsor a conference on diet and ADHD; and (4) the Food and Drug Administration should require certain new and existing additives to be tested. Appendices include further information on sugar and ADHD, diet and behavior, diet and ADHD, and food sensitivity. A guide for parents is included. (Contains 136 references.) (CR)
  85. Janssen PL, Hollman PC, Reichman E, Venema DP, van Staveren WA, Katan MB. 1996. Urinary salicylate excretion in subjects eating a variety of diets shows that amounts of bioavailable salicylates in foods are low. Am J Clin Nutr. 64(5):743–747.
    Intake of acetylsalicylic acid reduces the risk of cardiovascular disease and is associated with a decreased risk for colorectal cancer. Amounts of salicylates in foods are thus of interest, but data are scarce and controversial. We gave 58 mumol (10.5 mg) pure acetylsalicylic acid or 66 mumol (9.1 mg) salicylic acid to six volunteers and recovered 77–80% in 24-h urine samples. Thus, urinary excretion is a valid indicator for intake of free forms of (acetyl)salicylic acid. To estimate the bioavailable salicylate contents of diets, we subsequently studied salicylate excretion in 17 volunteers from 14 countries and four continents who ate a wide variety of self-selected diets. Median 24-h urinary salicylate excretion was 10 mumol (range: 6–12 mumol). Values increased with the fiber content of the diet (r = 0.73), suggesting that vegetable foods are the main sources of salicylates. However, amounts of salicylates in a variety of diets are evidently low and probably insufficient to affect disease risk.
  86. Venema DP, Hollman PCH, Janssen KPLTM, Katan MB. 1996. Determination of acetylsalicylic acid and salicylic acid in foods, using HPLC with fluorescence detection. J Agric Food Chem. 44(7):1762–1767.
    We developed a specific and sensitive HPLC method with fluorescence detection for the determination of free acetylsalicylic acid, free salicylic acid, and free salicylic acid plus salicylic acid after alkaline hydrolysis (free-plus-bound) in foods. Acetylsalicylic acid was detected after postcolumn hydrolysis to salicylic acid. With the method for free acetylsalicylic acid and salicylic acid, recovery was 95−98% for acetylsalicylic acid added to foods and 92−102% for salicylic acid. Recovery of added salicylic acid was 79−94% for the free-plus-bound salicylic acid method. The limit of detection was 0.02 mg/kg for fresh and 0.2 mg/kg for dried foods for all substances. We did not find acetylsalicylic acid in any of 30 foods previously thought to be high in salicylates. The contents of free-plus-bound salicylic acid and of free salicylic acid ranged from 0 to 1 mg/kg in vegetables and fruits and from 3 to 28 mg/kg in herbs and spices. Thus the tested foods did not contain acetylsalicylic acid and only small amounts of salicylic acid. Our data suggest that the average daily intake of acetylsalicylic acid from foods is nil and that of salicylic acid is 0−5 mg/day.
  87. Joss JD, LeBlond RF. 2000. Potentiation of warfarin anticoagulation associated with topical methyl salicylate. Ann Pharmacother. 34(6):729–733.
    OBJECTIVE: To report a case of international normalized ratio (INR) elevation resulting from the administration of topical methyl salicylate in a patient whose INR was previously stable while she received warfarin anticoagulation. CASE SUMMARY: A 22-year-old white woman presented with an INR of 12.2 after applying a topical pain-relieving gel to her knees daily for eight days. The potentiation of the warfarin anticoagulation was attributed to the low-dose methyl salicylate contained in the product. DISCUSSION: Methyl salicylate is systemically absorbed through the skin in measurable amounts, and may increase warfarin action by affecting vitamin K metabolism or by displacing warfarin from protein-binding sites. While several investigators have reported this interaction with use of high-dose methyl salicylate, this case indicates that a significant interaction can occur with the use of lower topical doses of methyl salicylate as well. CONCLUSIONS: Healthcare providers and patients taking warfarin must be aware of the potential hazard of using topical methyl salicylate in combination with warfarin.
  88. Kakehata S, Santos-Sacchi J. 1996. Effects of salicylate and lanthanides on outer hair cell motility and associated gating charge. J Neurosci. 16(16):4881–4889.
    Salicylate, one of the most widely used drugs, is known to induce reversible tinnitus and hearing loss. Salicylate interferes with outer hair cells (OHCs), which are believed to underlie normal auditory frequency selectivity and sensitivity. In the present experiments, the effects of salicylate and lanthanides on OHC motility and nonlinear capacitance were investigated by using isolated guinea-pig OHCs while attempting to avoid inadvertent intracellular pressure change, which itself can affect OHC motility and capacitance. Either extracellularly or intracellularly applied salicylate reduced nonlinear peak capacitance (Cmpk) and shifted the voltage at peak capacitance to depolarized levels. Concentration-response curves for reduction in Cmpk by salicylate and GdCl3 revealed a half-maximal concentration and Hill coefficient of 1.6 mM and 1.0, and 0.6 mM and 1.2, respectively. In comparable groups of OHCs, the normal Cmpk values of which were near 40 pF, average Cmpk decreased to 28 and 36 pF for intracellularly and extracellularly applied salicylate, respectively. Salicylate reduced, but did not completely block, the voltage-induced length change. Extracellularly, but not intracellularly, applied lanthanide blocked voltage-induced movement and capacitance almost completely. After intracellular trypsin treatment, salicylate reduced voltage-dependent capacitance reversibly, suggesting that salicylate directly acts on the sensor/motor and not via effects on intracellular structures, such as the subsurface cisternae. The results are consistent with the hypothesis that the dissociated, charged form of salicylate directly interacts with the sensor/motor on the inner aspect of the OHC plasma, whereas lanthanides interact on the outer aspect.
  89. Kalinke DU, Wüthrich B. 1999. Purpura pigmentosa progressiva in type III cryoglobulinemia and tartrazine intolerance. A follow-up over 20 years. Hautarzt. 50(1):47–51.
    A 58 year old patient with hepatitis virus C (HCV) infection had a secondary polyclonal IgG-IgM cryoglobulinemia with a benign 20 year course. Clinically the patient suffered from progressive pigmented purpura (PPP). Histologic evaluation revealed a lymphocytic vasculitis. Food containing tartrazine triggered flares of the PPP, as demonstrated with controlled oral provocation testing. In most of the previously described cases of HCV and type III cryoglobulinemia, the typical cutaneous finding was palpable purpura with leukocytoclastic vasculitis.
  90. Kato H, Ohta T, Tsugita T, Hosaka Y. 1983. Effect of parboiling on texture and flavor components of cooked rice. J Agric Food Chem. 31(4):818–823.
  91. Kawashima Z, Flagg RH, Cox DE. 1975. Aspirin-induced oral lesion: report of case. J Am Dent Assoc. 91(1):130–131.
    Aspirin is one of the most extensively used medications and has many beneficial effects. However, its injudicious use can produced local as well as systemic undesirable effects. A case of aspirin burn of the oral mucosa is presented. The lesion was in an unusual location. However, the history and the successful results from discontinuance of the drug supported the provisional diagnosis.
  92. Kim K, Tsao R, Yang R, Cui S. 2006. Phenolic acid profiles and antioxidant activities of wheat bran extracts and the effect of hydrolysis conditions. Food Chem. 95(3):466–473.
    Four different types of wheat bran were extracted and analyzed for phenolic acids using the Folin–Ciocalteu method and HPLC. The extracts and their hydrolysis products were also evaluated for their antioxidant activities. The total phenolic content of the red wheat bran was higher than that of the white wheat. We found that the majority of the phenolic acids existed in a bound form in wheat bran. These phenolic acids can be released by hydrolyzing the bran under alkaline or acidic conditions; however, the former was more efficient in the release of free phenolic acids than the latter. Ferulic, vanillic, and syringic acids were the major individual phenolic acids in the studied wheat bran. The main portion of the total ferulic acid was from alkaline hydrolysis. The alkaline hydrolysable fractions had greater antioxidant activities, while the acid hydrolysable fractions showed lower activities in both the red and white bran. The antioxidant activity of bran extract was stronger than that of free phenolic acids. 
  93. Klein AD, Penneys NS. 1988. Aloe vera. J Am Acad Dermatol. 18(4 Pt 1):714–720.
    We review the scientific literature regarding the aloe vera plant and its products. Aloe vera is known to contain several pharmacologically active ingredients, including a carboxypeptidase that inactivates bradykinin in vitro, salicylates, and a substance(s) that inhibits thromboxane formation in vivo. Scientific studies exist that support an antibacterial and antifungal effect for substance(s) in aloe vera. Studies and case reports provide support for the use of aloe vera in the treatment of radiation ulcers and stasis ulcers in man and burn and frostbite injuries in animals. The evidence for a potential beneficial effect associated with the use of aloe vera is sufficient to warrant the design and implementation of well-controlled clinical trials.
  94. Kochhar KP. 2008. Dietary spices in health and diseases: I. Indian J Physiol Pharmacol. 52(2):106–122. are heterogeneous collections of a wide variety of volatile and non-volatile staple dietary additives. India with its wide climatic conditions and topographical features naturally possesses wide variety of medicinal flora. Spices have a diverse array of natural phytochemicals that have complementary and overlapping actions, including antioxidant effects, modulation of detoxification enzymes, stimulation of immune system, reduction of inflammation, modulation of steroid metabolism and antibacterial and antiviral effects. In the present essay, various studies on effects of different well characterized spices on molecular, cellular, autocrine, paracrine and endocrine mechanisms and their role in neuromodulation, immunoinodulation, anti inflammatory, antioxidant, anti-carcinogenic, antimutagenic and psychoactive phenomena have been reviewed.
  95. Kurowski M, Brune K. 1992. Other unwanted side effects and drug interactions with aspirin and other salicylates. Aspirin, Vane OSE, Rm B, editors. Chapman and Hall.
    This work deals in a comprehensive way with the pharmacology of aspirin and the scientific discoveries made possible by the use of aspirin and aspirin-like drugs. It covers the pharmacokinetics and pharmacology of aspirin and salicylates, therapeutic applications and unwanted effects.
  96. Lanas A. 2001. Cyclo-oxygenase-1/cyclo-oxygenase-2 non-selective non-steroidal anti-inflammatory drugs: epidemiology of gastrointestinal events. Dig Liver Dis. 33:S29–S34.
    Non-steroidal anti-inflammatory drug use is associated with gastrointestinal side-effects including complications such as bleeding and perforation, which occur in 1–2% of patients after 6–12 months of therapy. A high level of non-prescription non-steroidal anti-inflammatory drug use is observed among those presenting complications. More common side-effects are symptomatic gastro-duodenal ulcers (annual incidence of 4–8%) and dyspepsia (25–50%). Low-dose aspirin use is also associated with an increased risk of upper gastrointestinal bleeding, but the increase is about 3 times lower than that found with common non-steroidal anti-inflammatory drugs. Recent studies suggest that the risk of bleeding in patients taking preferential cyclooxygenase-II inhibitors (e.g. nimesulide) is similar to that in patients taking non-selective non-steroidal anti-inflammatory drugs. Epidemiological studies have also shown that nitric oxide donors and antisecretory drugs reduce the risk of upper gastrointestinal bleeding both in non-steroidal anti-inflammatory drug and low-dose aspirin users.
  97. Lawrence VA, Loewenstein JE, Eichner ER. 1984. Aspirin and folate binding: in vivo and in vitro studies of serum binding and urinary excretion of endogenous folate. J Lab Clin Med. 103(6):944–948.
    To clarify the effect of aspirin on folate balance, we studied serum concentration, protein binding, and urinary excretion of endogenous folate. A healthy woman twice followed an 11-day protocol of constant diet, blood sampling twice daily, collection of all urine, and 650 mg of aspirin by mouth every 4 hours on the middle 3 days. As determined by equilibrium dialysis and Lactobacillus casei assay, aspirin induced a brisk, significant but reversible fall in total and bound serum folate and a small but insignificant rise in urinary folate excretion. Aspirin in vitro also displaced significant amounts of bound serum folate. Thus, aspirin in therapeutic doses can contribute to subnormal serum folate values, and if it increases urinary folate excretion even slightly, may impair folate balance.
  98. Matsuyoshi N, Keiji OHTA, Horiguchi Y, Imamura S. 1998. Drug eruption due to Bufferin® showing erythema exsudativum multiforme with a photo-recall-like phenomenon. European Journal of Dermatology. 8(4):280–2.
    A 21-year-old woman who had been taking several kinds of analgesics to treat dysmenorrhea developed episodic attacks of a purpuric macular eruption and a burning sensation on unexposed areas of the upper chest and back where she had sustained severe sunburn eight months earlier. Target-like lesions developed on these areas after intake of Bufferin®, a combination of aspirin and dialuminate. After the eruptions had abated following systemic administration of a corticosteroid agent, a challenge test was performed, using a quarter of a tablet of Bufferin®. The patient developed a temporary burning sensation and a erythematous color on the previously sunburned skin. We diagnosed this case as a drug eruption due to Bufferin® showing erythema exsudativium multiforme with a photo-recall-like phenomenon. In our case, skin tests would be useful to confirm the causal drug.
  99. Lemesh RA. 1993. Accidental chronic salicylate intoxication in an elderly patient: major morbidity despite early recognition. Vet Hum Toxicol. 35(1):34–36.
    Chronic salicylate intoxication represents an unappreciated form of self-poisoning in the elderly and therefore poses a diagnostic challenge. This report describes an elderly female with chronic salicylism who presented with unexplained delirium, dysarthria, diminished short-term memory and hearing, and urinary and fecal incontinence. She was treated with intravenous hydration, urinary alkalinization, and subsequent hemodialysis for persistent aciduria, acidemia and impending circulatory collapse. Major morbidity included myocardial infarction, life-threatening dysrhythmias, and mixed bacterial urosepsis. This report highlights the need to maintain a high index of suspicion for salicylate poisoning in the elderly, who commonly present with nonfocal neurologic features.

Research articles supporting that salicylates may improve health

Know your risks, if you're eliminating them from your diet

  • The Aspirin Foundation Lots of great information on this site.
  • Paterson JR, Lawrence JR. Salicylic acid: a link between aspirin, diet and the prevention of colorectal cancer. QJM. 2001;94(8):445–448. doi:10.1093/qjmed/94.8.445. View full article:
  • Sivagnanam P, Koutsoumpas A, Forbes A. Respiratory symptoms in patients with inflammatory bowel disease and the impact of dietary salicylates. Dig Liver Dis. 2007;39(3):232–239. doi:10.1016/j.dld.2006.08.001.  View abstract at:
    • This article talks about the relationship between IBD and respiratory illness. Choosing participants that had both issues, they surveyed how many salicylates they consumed in a week (using Swain's et al. 1985 study). Participants had mixed results, and over the entire group, as people ate fewer salicylates, energy levels also decreased. In some cases, patients found better relief continuing their normal salicylate medicines (up to 1600mg daily for a therapeutic dose) for both their repiratory and IBD issues. In the case of the low-salicylate diet, patients with ulcerative colitis saw a little better results than those with Chron's disease.
      • I would like to challenge some things about this paper.
        • Since 2006, better test results have come out for foods, and many foods that were low on Swain's study have been moved into medium and high categories. This means that the patients were likely eating a way higher salicylate diet than they thought they were.
        • Second, free and bound salicylates were not taken into consideration (no research studies supported that prior to 2006). This means that they were not looking at the full potential of salicylates in the body.
        • Third, the daily intake level was averaged 22-37mg of salicylates a week. Personally, I've keep my levels below 0.5mg/weekly. It is possible that there is a maximum for some people. I know if I were to eat higher than 1-2/week my IBS symtoms would return.
        • Fourth, they did not ask the participants to do a fragrant-free home regimen, switch out their toothpaste, or ask coworkers in the offices to not wear perfumes. Personally, I will get stomach problems just from someone wearing perfume at work, within 45 minutes or so. In order to test this appropriately, you have to consider all the different ways people consume salicylates, not just what gets put into the mouth.
        • Like all of the other studies I've read, the sample size was quite small. with fewer than 150 people.
        • The last thing is that this study was done to in a way to "find a cure" or suitable treatment for IBD. I don't think that all IBD patients are salicylate sensitive and there are probably many factors that contribute to it. We are looking at the symptoms only. Even if only 5% of IBD patients improved by eliminating salicylates (let's say) on a global level, that's a really big deal. Even if only a few people improved, I'm sure those people are quite happy they tried out a low-sal diet.

If there is a research article you think should be listed here, please let me know.

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