PUBLISHED ARTICLES
Research is a big part of what we do at ZRT. The quality of our research, often in collaboration with scientists at esteemed research institutions, is evidenced by the many publications that have been accepted in peer-reviewed journals over the years.
This is a list of articles that have been published based on testing developed at ZRT Laboratory.
“Dried Blood Spots (DBS) as an Alternative to Venipuncture Serum for Testing Hormones.” Zava DT. Townsend Letter. January 2023:14-18.
Summary: Serum/plasma derived by conventional venipuncture blood draw has been the mainstay for testing steroid, thyroid, and peptide hormones, blood lipids, and myriad other analytes associated with the endocrine system. Numerous reviews have been published, mostly over the past 20-30 years, on the pros and cons of finger-prick dried blood spot (DBS) versus venipuncture liquid serum/plasma for testing a broad spectrum of analytes. In this article, Dr. Zava discusses the advantages of DBS for testing endocrine biomarkers, several exceptions where DBS cannot be used, and why DBS is proving to be a convenient alternative to serum/plasma testing. View article.
"Mineral Nutrition of Samburu Adolescents: A Comparative Study of Pastoralist Communities in Kenya." Ionotti L, Lesorogol L, Olungah CO, Zava T, Needham B, Cui Y, Brindle E, Straight B. Am J Biol Anthropol. 2022;177(2):343-356.
Summary: This study looked at the mineral nutrition (copper, magnesium, selenium, and zinc) in Samburu pastoralist youth to see how cultural changes affected the youth's access to education, herding, and different food sources. The researchers collected dried blood spot samples from 161 youth and used Inductively Coupled Mass Spectrometry to measure the mineral concentrations. The youth's dietary intake and anthropometric measures were also assessed. The results showed that almost half of the adolescents had low levels of zinc, and most had a low zinc-to-copper ratio. They also had a high probability of inadequate nutrient intake for protein, fat, vitamins A, B12, C, and E. The study found that where the youth lived, livestock ownership, meat and vegetable consumption, protein intake, infectious disease, BMI, and hemoglobin levels all had an impact on their mineral nutrition. In recent years, the Samburu pastoralists have undergone many dietary changes due to market integration, drought, and conflict. Some youth have access to wild foods, while others are more vulnerable, especially girls who are actively herding. View article.
“Heavy metal blood concentrations in association with sociocultural characteristics, anthropometry and anemia among Kenyan adolescents.” Ashley-Martin J, Ionotti L, Lesorogol C, Hilton CE, Olunguh CO, Zava T, Needham BL, Cui Y, Brindle E, Straight B. Int J Environ Health Res. 2022;32(9):1935-1949.
Summary: The study measured dried blood spot heavy metal concentrations in 161 Kenyan adolescents and analyzed associations with sociocultural, demographic, health factors, and anthropometry. Results showed high concentrations of lead and cadmium compared to North American and European studies. The study highlights the need for further investigation into the sources of heavy metals in the community. Purchase article.
"Modulation of attention and stress with arousal: The mental and physical effects of riding a motorcycle." Vaughn DA, Maggiora MG, Vaughn KJ, Maggiora CJ, Tavakoli A-V, Liang W, Zava D, Cohen MS, Lenartowicz A. Brain Res. February 2021; 1752:147203.
Summary: Existing theories suggest that moderate arousal improves selective attention, as would be expected in competitive sports or sensation-seeking activities. We investigated how riding a motorcycle affects sensory processing. While participants were riding, we found a decrease in N1 amplitude, increase in mismatch negativity, and decrease in relative alpha power, together suggesting enhancement of sensory processing and visual attention. Riding increased epinephrine levels, increased heart rate, and decreased the ratio of cortisol to DHEA-S. Together, these results suggest that riding increases focus, heightens the brain’s passive monitoring of changes in the sensory environment, and alters HPA axis response. In general, our findings suggest that selective attention and sensory monitoring seem to be separable neural processes. View article.
“Topical Therapy with Estradiol, Progesterone, and Testosterone and Their Distribution in Saliva, Capillary Blood, Serum, and Urine.” Zava DT. Townsend Letter. January 2021:31-34.
Summary: Using data accumulated over many years of testing at ZRT Laboratory, this article demonstrates why saliva and capillary whole blood testing is more accurate than serum or urine tests to monitor sex hormone levels during topical hormone treatment. Purchase issue.
“Validation of dried blood spot sample modifications to two commercially available COVID-19 IgG antibody immunoassays.” Zava TT and Zava DT. Bioanalysis. 2020; Dec 15 [ePub ahead of print].
Summary: Two commercially available COVID-19 IgG antibody assays were modified for use with dried blood spot (DBS) and the assay successfully validated. Corresponding DBS and serum samples for the IRB-approved study showed excellent agreement, and the validation also included the effects of different sample drying and shipping conditions, among other variables that might affect the assay. View article.
“Salivary aldosterone and cortisone respond differently to high- and low-psychologically stressful soccer competitions.” McHale TS, Chee WC, Hodges-Simeon CR, Zava DT, Albert G, Chan KC, Gray PB. J Sports Sci. 2020;38:2688-97.
Summary: Saliva samples were taken from 102 Hong Kongese boys before and after a competitive soccer match (high stress situation) as well as before and after an intra-squad scrimmage (relatively lower stress). Aldosterone and cortisone were analyzed by LC-MS/MS at ZRT. The increase in aldosterone in both situations was greater in winning competitors than losing competitors, while cortisone increased in the higher stress match but decreased during the lower stress scrimmage. Purchase Article.
“Juvenile Children’s Salivary Aldosterone and Cortisone Decrease during Informal Math and Table-Tennis Competitions.” McHale TS, Gray PB, Hodges-Simeon CR, Zava D, Albert G, Chan KC, Chee WC. Adapt Human Behavior Phys. 2020;6:413-35.
Summary: Saliva samples were taken from Hong Kongese children before and after a math competition against classmates and before and after two back-to-back table tennis competitions. Aldosterone and cortisone were analyzed by LC-MS/MS at ZRT. In the math competition, decreases in aldosterone and cortisol were seen in boys and girls, but the decreases were greater in losing team members than winning team members. In the table tennis competition, results varied according to whether the match occurred at 8:30 or 11 a.m.. Aldosterone decreased in competitors during an 11 a.m. match, while cortisone decreased significantly only in the 8:30 a.m. match. Purchase Article.
“Reflecting on the Evidence: A Reply to Knight, McShane, et al.” Nave G, Daviet R, Nadler A, Zava D, Camerer C. Psychol Sci. 2020; 31:898-900.
Summary: This letter commented on an article which reported 3 experiments looking at testosterone’s effect on the Cognitive Reflection Test. The letter summarizes how differences in experimental design make it difficult to meaningfully compare results between the different studies. Purchase Article.
“Topical Progesterone, Not Synthetic Progestins or Oral Progesterone, Should Be Considered as A Companion for Estradiol Replacement Therapy to Lower Breast Cancer Risk.” Zava DT. Anti-Aging Medical News 2019;Winter:28-31.
Summary: Dr. Zava describes his rationale for recommending topical progesterone in physiological dosages as a breast and endometrial cancer preventive in women using menopausal estrogen therapy. See article within full issue.
“Concordance of Fingerstick and Venipuncture Sampling for Fertility Hormones.” Zava T, Harrington J, Zava DT. Obstet Gynecol. 2019;134(2):418.
Summary: This letter commented on an article which described a comparison of venipuncture and fingerstick sampling for testing fertility hormones, expressing some concerns about the study design, methodology, and interpretation of data. Purchase article.
“Does testosterone impair men's cognitive empathy? Evidence from two large-scale randomized controlled trials.” Nadler A, Camerer CF, Zava DT, Ortiz TL, Watson NV, Carré JM, Nave G. Proc Biol Sci. 2019;286(1910):20191062.
Summary: Saliva hormone assays were performed by LC-MS/MS and EIA at ZRT Laboratory in these two studies designed to test the effects of testosterone therapy on cognitive empathy. Previous studies that found testosterone impaired cognitive empathy had very low sample sizes. In the new studies, much larger sample sizes of 243 and 400 young men were used. In both experiments, the men were randomized to receive either testosterone gel transdermally or placebo gel, and cognitive empathy was assessed using the RMET (Reading the Mind in the Eyes Test). Saliva testosterone levels were greater in the men who received the testosterone gel than the placebo group. The experiments found no effect of testosterone treatment on cognitive empathy. See abstract.
“4-Hydroxy estrogen metabolite, causing genomic instability by attenuating the function of spindle-assembly checkpoint, can serve as a biomarker for breast cancer.” Miao S, Yang F, Wang Y, Shao C, Zava DT, Ding Q, Shi YE. Am J Transl Res. 2019;11(8):4992-5007.
Summary: This comprehensive study of sex hormone metabolism and risk of breast cancer looked at over 30 metabolites in dried urine samples from 42 premenopausal breast cancer patients and 37 healthy controls in mainland China. The authors found that the ratio of 4-hydroxy estrogen metabolites to total estrogen was the best predictor of breast cancer risk, whereas the ratio of 2-hydroxy estrone to 16α-hydroxyestrone was not a clear marker for breast cancer risk. See full article.
“Topical Delivery of Sex Steroid Hormones and Distribution in Different Body Fluids.” Zava DT. Anti-Aging Medical News 2019;Spring:20-23.
Summary: Dr. Zava discusses the subject of measuring sex steroid hormone levels after topical dosing and the appropriateness of different body fluids (saliva, dried blood spot, urine, and serum) for testing. He demonstrates, using results from tens of thousands of female and male patients who have used different topical doses of estradiol, progesterone, and testosterone, and subsequently tested saliva, dried blood spot, serum, and urine levels of these hormones, why serum and urine are not appropriate for monitoring therapy. See full issue.
“Ingestion of Steamed and Dehydrated Placenta Capsules Does Not Affect Postpartum Plasma Prolactin Levels or Neonatal Weight Gain: Results from a Randomized, Double-Blind, Placebo-Controlled Pilot Study.” Young SM, Gryder LK, Cross CL, Zava D, Norris W, Benyshek DC. J Midwifery Womens Health. 2019;64(4):443-450.
Summary: This randomized, double-blind, placebo-controlled trial investigated neonatal weight gain and maternal plasma prolactin levels during late pregnancy and early after birth in 27 women receiving a supplement of either dehydrated placenta or placebo. This was to investigate theories that consumption of dehydrated placenta can improve breast milk quality and quantity. Prolactin analyses were performed at ZRT. Plasma prolactin levels increased in both groups during the study period, but there were no differences between the placebo group and the placenta group in either prolactin levels or neonatal weight gain. See abstract.
“The relationship between progesterone, sleep, and LH and FSH secretory dynamics in early post-menarchal girls.” Sun BZ, Kangarloo T, Adams JM, Sluss P, Chandler DW, Zava DT, McGrath JA, Umbach DM, Shaw ND. J Clin Endocrinol Metab. 2019;104(6):2184-2194.
Summary: Hormone assays in dried blood spot and dried urine were carried out at ZRT for this study investigating menstrual cycle hormonal dynamics. The study found that although rising levels of progesterone in the follicular phase during late puberty slowed LH pulse frequency during sleep, there was a normal rise in FSH and normal follicle growth. Thus the effects of progesterone on LH secretion during sleep do not appear to affect FSH secretion and contribute to menstrual irregularity in girls in late puberty, and if sleep disturbances contribute to irregular cycles this is likely not due to a disruption in FSH dynamics. See abstract.
“Salivary steroid hormone responses to dyadic table tennis competitions among Hong Kongese juvenile boys.” McHale TS, Gray PB, Chan KC, Zava DT, Chee WC. Am J Hum Biol. 2018:30(6);e23190.
Summary: Hormone analyses were carried out at ZRT by liquid chromatography/tandem mass spectrometry in saliva samples from Chinese boys taking part in table tennis competitions. The boys were aged 8-11 and samples were collected before the warm-up for the matches and again after the second round of matches. Testosterone levels were too low to measure, and DHEA and androstenedione levels did not change after the match compared with pre-match levels. Cortisol levels decreased in the post-match samples. In contrast, cortisol and testosterone tend to rise in adult males during athletic competition. See abstract.
“Healthy Post-Menarchal Adolescent Girls Demonstrate Multi-Level Reproductive Axis Immaturity.” Sun BZ, Kangarloo T, Adams JM, Sluss PM, Welt CK, Chandler DW, Zava DT, McGrath JA, Umbach DM, Hall JE, Shaw ND. J Clin Endocrinol Metab. 2019:104(2):613-623.
Summary: This study looked at reasons for menstrual irregularity in the first few years after menarche in teenage girls. During 2 consecutive menstrual cycles levels of LH, FSH, estradiol, progesterone, and inhibin B were measured in serum; LH and FSH were measured in dried blood spots; and estradiol and pregnanediol were measured in dried urine strips, all 2-5 times per week. Findings showed that estradiol positive feedback, involving the hypothalamic-pituitary-ovarian axis, was impaired in girls who had short luteal phase cycles and anovulatory cycles. The study indicates that the achievement of reproductive axis maturity involves the development of proper coordination between the brain and ovary. See abstract.
“Iodine stimulates estrogen receptor signaling and its systemic level is increased in surgical patients due to topical absorption.” He S, Wang B, Lu X, Miao S, Yang F, Zava T, Ding Q, Zhang S, Liu J, Zava D, Shi YE. Oncotarget. 2018;9(1):375-384.
Summary: Urinary iodine levels were assessed at ZRT in this study evaluating the effects of excess iodine in breast cancer patients undergoing surgery. Antiseptic iodine use during breast surgery resulted in elevated urinary iodine compared to controls. The study also found a stimulatory effect of iodine on the transcriptional activity of estrogen receptor alpha in human breast cancer cells, both in vitro and in vivo. This may explain the observed elevations in risk of breast cancer in thyroid cancer patients treated with radioactive iodine. See full article.
“Digital Delivery of Meditative Movement Training Improved Health of Cigarette-Smoke-Exposed Subjects.” Payne P, Fiering S, Zava D, Gould TJ, Brown A, Hage P, Gaudet C, Crane-Godreau M. Front. Public Health. 2018;6:282.
Summary: High sensitivity CRP levels were measured at ZRT in dried blood spots to assess systemic inflammation, and hormone levels were measured in diurnal urine and saliva samples, in this study of flight attendants exposed to second-hand smoke. The flight attendants were randomized to receive either digitally-delivered meditative movement training (MM) or health education videos (controls) over 12 weeks. Improvements were seen in the MM group compared to the control group with respect to chronic lung symptoms, and they showed non-significant reductions in hs-CRP levels and increased DHEA-S levels. The MM intervention was determined to improve the overall health of the participants during the course of the study. See full article.
“Neonatal hormone concentrations and risk of testicular germ cell tumors (TGCT).” Morimoto LM, Zava D, McGlynn KA, Stanczyk FZ, Kang AY, Ma X, Wiemels JL, Metayer C. Cancer Epidemiol Biomarkers Prev. 2018;27:488-495.
Summary: Hormone levels were measured in dried blood spots by LC-MS/MS at ZRT for this population-based case-control study, which looked at the effect of sex steroid hormone imbalances during the early neonatal period on later TGCT development. Because of the long-term stability of dried blood spots, hormone levels in archived samples taken from newborns could be used to see whether infants and adolescents who were later diagnosed with TGCT had any notable imbalances at the time of birth. The results showed that higher androgen, in particular androstenedione, levels at birth were linked to increased TGCT risk in the adolescents, but not the infants. This suggested that the later development of TGCT was influenced by neonatal androgen imbalance. See abstract.
“Single-dose testosterone administration increases men's preference for status goods.” Nave G, Nadler A, Dubois D, Zava D, Camerer C, Plassmann H. Nature Communications 2018; 9(1):2433.
Summary: Testosterone levels were measured in 243 men aged 18-55, 4 hours after applying either testosterone gel or placebo gel to their skin. At the same time they participated in questionnaires designed to assess their attitudes towards ads for a variety of goods that emphasized aspects of the item’s association with social status, quality, level of luxury, or power. Results showed that men who received the testosterone had a stronger preference for luxury/status goods than the men who received placebo. See abstract.
“Coalitional Physical Competition: Acute Salivary Steroid Hormone Responses among Juvenile Male Soccer Players in Hong Kong.” McHale TS, Chee WC, Chan KC, Zava DT, Gray PB. Human Nature 2018;29(3):245-267.
Summary: Salivary androgens and cortisol were assessed in saliva samples from Chinese boys aged 8-11 years during a soccer match and a team soccer scrimmage. Testosterone did not change measurably. DHEA increased in most of the boys during both activities, while androstenedione increased during match play but not during the team scrimmage. Cortisol increased significantly during match play but decreased during the scrimmage, and the ratio of cortisol/DHEA also decreased during the scrimmage, indicating a more relaxed mental state when playing with familiar team members vs. a rival team. See abstract.
“Acute salivary steroid hormone responses in juvenile boys and girls to non-physical team competition.” McHale TS, Gray PB, K. Chan K, Zava DT, Chee W. Adaptive Human Behavior and Physiology 2018;4(3):223-247.
Summary: Hormonal responses were assessed in saliva samples from Chinese children aged 9-10 years during a team math competition. Testosterone and estradiol levels were too low to measure. Almost all competitors showed decreases in cortisol and the cortisol/DHEA ratio. The percentage change in cortisol was significantly lower in losers than winners and changes in DHEA and androstenedione were correlated with team performance measures. See abstract.
“Understanding the “Big 4” heavy metals – why sample type matters and some results can be misleading.” Zava TT. Anti-Aging Medical News Spring 2018: 82-86.
Summary: This article outlines the 4 heavy metals that are included in the top 10 most toxic substances according to the Agency for Toxic Substances and Disease Registry, namely arsenic, lead, mercury, and cadmium. It details the information that can be derived from lab testing for these 4 elements, how testing assesses exposure and what the implications are for health. It outlines the most appropriate body fluid to test for exposure to each heavy metal and why sample type is important for proper assessment of exposure. For example, urine levels of mercury or cadmium indicate cumulative past exposure to the element, whereas dried blood spot levels of these elements are indicative of recent exposure only. Lead can only be determined in dried blood spot, and arsenic can only be determined in urine, for proper assessment of exposure to these elements. See full issue.
“Sex hormone metabolism and threatened abortion.” Xu Q, Chen J, Wei Z, Brandon TR, Zava DT, Shi YE, Cao Y. Med Sci Monit. 2017;23:5041-5048.
Summary: Sex hormone metabolites were assessed using GC-MS/MS in urine from 73 women 6-8 weeks into pregnancy. Thirty-four of the women had vaginal bleeding, indicating threatened miscarriage, and 39 did not. The levels of estrogen and androgen metabolites in the women with vaginal bleeding were significantly lower than in those who were not bleeding, suggesting reduced estrogenic activity that could have led to the vaginal bleeding in the women with threatened miscarriage. See full article.
"Single-dose testosterone administration impairs cognitive reflection in men.” Nave G, Nadler A, Zava D, Camerer C. Psychol Sci 2017; 28(10):1398-1407.
Summary: In 243 men aged 18-55, a Cognitive Reflection Test (CRT) was administered after applying either testosterone gel or placebo gel to their skin. CRT scores were lower in the men who had received testosterone than in those who received placebo, suggesting that testosterone affected the men’s ability to make appropriate judgments and decisions. See abstract.
“Effects of placentophagy on maternal salivary hormones: A pilot trial, part 1.” Young SM, Gryder LK, Cross C, Zava D, Kimball DW, Benyshek DC. Women Birth 2018;31(4):e245-e257.
Summary: ZRT used liquid chromatography/tandem mass spectrometry to test levels of 17 hormones in both saliva and placental tissue of 27 women who were randomly assigned to receive capsules containing either their dehydrated and homogenized placenta or placebo in the early postpartum period. While salivary hormone levels overall did not differ significantly between the placenta or placebo groups after consuming the capsules, there was a small but significant dose-response relationship between saliva and placental levels of all 15 hormones detected in the placental tissue that was not observed in the placebo group. Despite these small increases in hormone levels after placentophagy, the study did not evaluate any therapeutic effects. See abstract.
“Placentophagy's effects on mood, bonding, and fatigue: A pilot trial, part 2.” Young SM, Gryder LK, Cross C, Zava D, Kimball DW, Benyshek DC. Women Birth 2018;31(4):e258-e271.
Summary: Maternal mood, bonding, and fatigue were assessed in 27 women who were randomly assigned to receive capsules containing either their dehydrated and homogenized placenta or placebo in the early postpartum period. While there were no significant differences between the placenta or placebo groups overall, analyses at different time points suggested some evidence of a decrease in depressive symptoms and reduced fatigue in the group that consumed placenta compared to placebo. ZRT performed the hormone analyses in Part 1 of this study. See abstract.
“Effectiveness of a Novel Qigong Meditative Movement Practice for Impaired Health in Flight Attendants Exposed to Second-Hand Cigarette Smoke.” Payne P, Fiering S, Leiter JC, Zava D, Crane-Godreau M. Front Hum Neurosci 2017;11:67.
Summary: This pilot study used ZRT testing for hs-CRP and Vitamin D in dried blood spot as part of an evaluation of a meditative movement practice to improve health outcomes in 14 flight attendants who were exposed to second-hand smoke before smoking was banned on commercial flights. The Qigong intervention improved lung health measures such as autonomic function, exercise tolerance, and cardiopulmonary function, and reduced systemic inflammation, and there was more than a 50% reduction in average hs-CRP levels (a marker of inflammation). Vitamin D levels did not change. See full article.
“Effects of Human Maternal Placentophagy on Maternal Postpartum Iron Status: A Randomized, Double-Blind, Placebo-Controlled Pilot Study.” Gryder LK, Young SM, Zava D, Norris W, Cross CL, Benyshek DC. J Midwifery Women’s Health 2017;62:68-79.
Summary: This study investigated the efficacy of encapsulated placenta as a source of dietary iron in pregnant women. Hemoglobin, transferrin, and ferritin levels were used as markers of iron status in blood samples drawn during the 36th week of pregnancy, within 96 hours of birth, between days 5-7 postpartum, and during the 3rd week after birth, in women treated with either encapsulated placenta or placebo capsules. The results showed that encapsulated placenta did not significantly change iron status compared to placebo, and was therefore not an adequate source of supplemental iron. See article abstract.
“Presence and concentration of 17 hormones in human placenta processed for encapsulation and consumption.” Young SM, Gryder LK, Zava D, Kimball DW, Benyshek DC. Placenta 2016; 43:86-89.
Summary: This is the first study to use state-of-the-art LC-MS/MS methodology to analyze the levels of 17 hormones in placenta samples that had been processed for encapsulation from 28 women who had opted to ingest their postpartum placentas in this form. The benefits of this practice are said to include the fact that hormones contained in the placenta extracts can relieve depressive symptoms and improve milk production. Results showed detectable levels of 16 of the 17 hormones in the placenta samples, and their content of estradiol, progesterone, and allopregnanolone could potentially reach physiological level thresholds after ingestion. Purchase full article.
“Meditative Movement as a Treatment for Pulmonary Dysfunction in Flight Attendants Exposed to Second-Hand Cigarette Smoke: Study Protocol for a Randomized Trial.” Payne P, Zava D, Fiering S, Crane-Godreau M. Front Psychiatry 2016;7:38.
Summary: This is the protocol for a study that will use ZRT testing in saliva (steroid hormones), dried blood spot (hs-CRP, HbA1c, TSH, Vitamin D), and dried urine (cortisol, cortisone, melatonin, elements) as part of an evaluation of a wide range of physiological systems in flight attendants who were exposed to second-hand smoke before smoking was banned on commercial flights. See full article.
“Physical Competition Increases Dehydroepiandrosterone (DHEA) and Androstenedione rather than Testosterone among Juvenile Boy Soccer Players.” McHale TS, Zava DT, Hales D, Gray PB. Adaptive Human Behavior & Physiology, 2016;2:44-56.
Summary: Using highly sensitive liquid chromatography/tandem mass spectrometry, the saliva steroids DHEA, androstenedione, cortisol, and testosterone were assayed in saliva samples from boys aged 8-10 collected during soccer practice and soccer match competition. Testosterone levels were below the sensitivity of the assay in most cases (<3 pg/mL), but a statistically significant rise in DHEA was seen during both practice and match play, while androstenedione significantly increased during match play only. Cortisol/DHEA ratios were calculated, and these showed a significant decrease during practice but not during match play. This is the first known study of the impact of athletic competition on salivary steroids in juvenile boy athletes, and it indicates that adrenal hormone release is affected by physical competition and is different to hormonal changes seen in adult males. See full article.
“Vitamin D Deficiency and Its Predictors in a Country with Thirteen Months of Sunshine: The Case of School Children in Central Ethiopia.” Wakayo T, Belachew T, Vatanparast H, Whiting SJ. PLoS ONE, 2015;10(3):e0120963.
Summary: ZRT’s blood spot vitamin D testing was used in this study examining vitamin D status in schoolchildren living in the sunny climate of Ethiopia. Vitamin D deficiency, defined as 25-hydroxyvitamin D levels <50 nmol/L (equivalent to <20 ng/mL) was significantly more prevalent in children living in an urban environment (61.8%) compared with those in a rural setting (21.2%). Significant predictors of vitamin D deficiency included body fatness, having a TV/computer at home, maternal education, and socioeconomic status. This study highlights lifestyle factors that can predispose people to vitamin D deficiency even in countries with high sun exposure. See full article.
"Associations Between Vitamin D Levels and Depressive Symptoms in Healthy Young Adult Women." Kerr DCR, Zava DT, Piper WT, Saturn SR, Frei B, Gombart AF. Psych Res 2015;227:46-51.
Summary: To investigate the relationship between vitamin D sufficiency and depression, 180 healthy young women completed surveys to assess depressive symptoms at baseline and then once a week for 4 weeks, and serum vitamin D levels were determined at baseline and 4 weeks. A high rate of vitamin D insufficiency, defined as levels <30 ng/mL, was seen, occurring in 42% and 46% of the women at baseline and week 4, respectively. Lower vitamin D levels were related to clinically significant depressive symptoms. Purchase full article.
"A Pilot Study Evaluating the Effectiveness of a Mindfulness-Based Intervention on Cortisol Awakening Response and Health Outcomes Among Law Enforcement Officers." Christopher MS, Goerling RJ, Rogers BS, Hunsinger M, Baron G, Bergman AL, Zava DT. J Police Criminal Psych 2015;31:15-28.
Summary: The effectiveness of an 8-week mindfulness-based resilience training program was studied in 43 police officers to determine its potential for mitigating job-related stress. Cortisol was tested in saliva samples collected 0, 30, and 45 minutes after waking on a day prior to starting the program, and again within 5 days after completing the program, to assess the cortisol awakening response as a stress marker. The program significantly improved mindfulness, resilience, stress, burnout, emotional factors, and mental and physical health. The cortisol awakening response was not significantly different after the program compared to before, however the area under the curve for cortisol at the three time points was lower after the program and correlated significantly with the improvement in mental health symptoms. Purchase full article.
"Steroid Hormone Testing in Different Body Fluids." Zava DT. Townsend Letter 2015; January.
Summary: This article examines the issues surrounding hormone testing for progesterone after topical delivery. Despite demonstrable clinical efficacy, serum and urine progesterone levels do not increase after application of topical progesterone, whereas saliva and capillary blood spot tests do show a dose-dependent increase that indicates efficient tissue uptake of the hormone. The article concludes that saliva and capillary blood spot testing, but not serum or urine testing, can be used to monitor topical progesterone therapy. See full article.
“Proinflammatory Cytokines and DHEA-S in Women with Fibromyalgia: Impact of Psychological Distress and Menopausal Status.” Sturgeon JA, Darnall BD, Zwickey HL, Wood LI, Hanes DA, Zava DT, Mackey SC. J Pain Res, 2014;7:707-16.
Summary: Serum levels of proinflammatory cytokines (interleukins 6, 8, and 10 and TNF-α) and blood spot DHEA-S were measured in pre- and postmenopausal women suffering from fibromyalgia, and their relationships with reported pain intensity and level of psychological distress were examined. There were significant relationships between IL-8 and pain-related symptoms and depression, and the ratio of IL-6 to IL-10 was significantly lower in individuals with greater levels of depressive symptoms. Although the decline in DHEA-S levels with age has been suggested to be related to the onset of fibromyalgia symptoms across the lifespan, in this study DHEA-S levels did not correlate with pain intensity, psychological distress or cytokine levels. See full article.
"The trouble with topical progesterone and testing." Zava DT. Townsend Letter 2014; January.
Summary: This article examines the issues surrounding hormone testing for progesterone after topical delivery. Despite demonstrable clinical efficacy, serum and urine progesterone levels do not increase after application of topical progesterone, whereas saliva and capillary blood spot tests do show a dose-dependent increase that indicates efficient tissue uptake of the hormone. The article concludes that saliva and capillary blood spot testing, but not serum or urine testing, can be used to monitor topical progesterone therapy. See full article.
"Editorial: Percutaneous absorption of progesterone." Zava DT, Groves MN, Stanczyk FZ. Maturitas 2014; 77:91-92.
Summary: This editorial discusses the absorption of progesterone when applied to the skin in topical formulations, referring to our study recently published in Menopause (Du et al., 2013). A reliance on serum levels to assess progesterone absorption from topical formulations could lead to over-use of progesterone in an attempt to achieve levels that counteract the proliferative actions of estrogens used in menopausal hormone therapy. Saliva and capillary blood spot are better choices than serum testing for topically delivered progesterone. Purchase full article.
"Theodore Zava Responds.” Zava TT. Townsend Letter 2013; November.
Summary: This is a response to a letter criticizing the conclusions made in our previous article, published in Townsend Letter in January 2013, concerning evaluation of the iodine loading test. The response answers all of the concerns raised in this letter and urges its authors to ensure that their patients are correctly assessed for whole-body iodine sufficiency. See full article.
"Percutaneous progesterone delivery via cream or gel application in postmenopausal women: a randomized cross-over study of progesterone levels in serum, whole blood, saliva, and capillary blood." Du JY, Sanchez P, Kim L, Azen CG, Zava DT, Stanczyk FZ. Menopause 2013; 20(11):1169-1175.
Summary: Saliva, capillary blood spot, serum, and whole venous blood levels of progesterone were measured after application of progesterone cream or gel in 10 postmenopausal women in this randomized, cross-over study using ZRT testing. While serum and whole venous blood levels rose slightly, peaking at around 8 hours after application, saliva levels peaked earlier and were 10 fold higher than serum and venous whole blood levels; capillary blood spot levels were 100-fold higher than serum and whole venous blood, peaking at 8 hours after application. The much higher levels in saliva and blood spot than in serum and venous blood indicate a high level of absorption of progesterone cream and its transport to tissues, and demonstrate the lack of utility of serum measurements, which underestimate progesterone absorption, to monitor topical progesterone treatment. See article abstract.
"Evaluation of the Iodine Loading Test: Urine Iodine Excretion Kinetics after Consumption of 50 mg Iodine/Iodide." Zava T. Townsend Letter 2013; January.
Summary: This study at ZRT Laboratory analyzed iodine excretion before and after a 50 mg loading dose of iodine/iodide, to determine whether a popular "iodine loading test" can accurately determine iodine sufficiency. The study concluded that the cutoff of 90% excretion used in this test does not allow it to realistically assess whole body iodine sufficiency or deficiency. See full article.
“Iodine and creatinine testing in urine dried on filter paper.” Zava TT, Kapur S, Zava DT. Anal Chim Acta 2013; 764:64-69.
Summary: This paper describes ZRT Laboratory’s novel test in dried urine for iodine and creatinine. This test makes urine collection for iodine testing simple and convenient, unlike typical liquid urine collections over 24 hours. See full article.
"Testosterone implants in women: Pharmacological dosing for a physiologic effect." Glaser R, Kalantaridou S, Dimitrakakis C. Maturitas 2013;74(2):179-84.
Summary: ZRT dried blood spot testing was used in this study investigating testosterone levels in women who received subcutaneous testosterone implants. Testosterone levels were found to fluctuate throughout the day in a similar manner to the circadian variation seen with endogenous testosterone release. See article abstract.
"Vitamin D Supplement Doses and Serum 25-Hydroxyvitamin D in the Range Associated with Cancer Prevention." Garland CF, French CB, Baggerly LL, Heaney RP. Anticancer Research 2011; 31(607-612).
Summary: This study used ZRT's Vitamin D testing to examine the relationship of measured vitamin D status to vitamin D supplementation, both as practiced by health conscious individuals and as related to cancer prevention. See full article.
"Assessment of Japanese iodine intake based on seaweed consumption in Japan: A literature-based analysis." Zava TT, Zava DT. Thyroid Res 2011; 4 (1):14.
Summary: This thorough review of the pertinent literature clears up much of the confusion surrounding the iodine content of the Japanese diet. The authors present a combined analysis based on dietary recall studies, surveys, urinary iodine testing, and the iodine content of various seaweeds, and estimate the average Japanese iodine intake to be between 1 and 3 milligrams per day. See full article.
“Agreement of blood spot card measurements of vitamin D levels with serum, whole blood specimen types and a dietary recall instrument.” Larkin EK, Gebretsadik T, Koestner N, Newman MS, et al. PloS ONE 2011;6(1).
Summary: This study found relatively good agreement between 25-hydroxy vitamin D measurements using blood spot cards, serum, and whole blood samples. The authors note that dried blood spot samples are less invasive than traditional venipuncture and provide a convenient method for assessing vitamin D status in population studies and in children. See full article.
“Low salivary testosterone levels in patients with breast cancer.” Dimitrakakis C, Glaser R, Zava D, Marinopoulos S, Tsigginou A, Antsaklis A. BMC Cancer 2010; 10(547):1-8.
Summary: The role of endogenous hormones in breast cancer was studied using saliva testing of 347 women with breast cancer and 184 age-matched control women. The women with breast cancer had significantly lower salivary testosterone, estriol, and DHEA-S levels than the controls, while estradiol and estrone levels were higher in the breast cancer cases than the controls. The authors suggest that bioavailable testosterone protects against the proliferative effects of estrogens on breast tissue. See full article.
"Female social and sexual interest across the menstrual cycle: the roles of pain, sleep and hormones.” Guillermo CJ, Manlove HA, Gray PB, Zava DT, Marrs CR. BMC-Womens Health 2010; 10(19):1-10.
Summary: Saliva testing was used to study changing hormone levels throughout the menstrual cycle in healthy women, who were either taking oral contraceptives or were not using oral contraceptives. Hormones tested were DHEA-S, progesterone, cortisol, testosterone, estradiol, and estriol. Estrogen levels correlated with socio-sexual and physical activity during menstruation and the luteal phase in the non-OC users, but these activities were more closely associated with progesterone, cortisol, and DHEA-S in the OC users throughout the cycle. OC users showed higher overall social and physical attraction. The authors conclude that a broader range of hormones could be associated with sexual attraction than previously thought. See full article.
“Postprandial insulin and triglycerides after different breakfast meal challenges: use of finger stick capillary dried blood spots to study postprandial dysmetabolism.” Kapur S, Groves MN, Zava DT, Kapur S. Journal of Diabetes Science and Technology 2010; 4(2):236-243.
Summary: Dried blood spot technology was used to study the phenomenon of postprandial dysmetabolism, which has been characterized by sustained high levels of insulin and triglycerides in the blood after eating. This has been found to increase risk of atherosclerosis and coronary heart disease, but routine monitoring of dysmetabolism in the general population is hampered by the inconvenience of blood collection. The study demonstrated the ease of repeated blood spot collection at various times after eating typical breakfast meals. It also showed differences in levels of insulin and triglycerides after eating the different meals, which varied in nutritional content. Dried blood spots were found to be a convenient and simple tool to look at the effects of different diets on postprandial dysmetabolism. This method could therefore be used in larger-scale studies of the effects of diet on cardiometabolic risk. See article abstract. To purchase the full article, visit the journal’s website at www.jdst.org
“Poster presentation report: safety of maternal testosterone therapy during breast feeding.” Glaser RL, Newman M, Parsons M, Zava D, Glaser-Garbrick D. International Journal of Pharmaceutical Compounding, 2009: 13(4):314-7.
Summary: This article summarizes a poster presentation from the 13th Annual International Congress on Steroidal Hormones and Cancer in September 2008 (the poster is included in the list below). The study found that in a woman undergoing testosterone supplementation for relief of depression, anxiety, irritability, memory loss, aches, and pains, testosterone was not passed on to her nursing infant during breast feeding. Blood spot testosterone levels were measured in the mother, her infant, and breast milk. Testosterone levels were increased during therapy in the mother’s blood, but not in the breast milk or in the infant’s blood. See article abstract. To purchase the full article, visit the journal’s website at www.ijpc.com
“The physiologic role and use of estriol.” Paoletti JE. International Journal of Pharmaceutical Compounding, 2009: 13(4):270-5.
Summary: Estriol is one of the three main circulating estrogens in the body. The author explains the role of estriol in the body, particularly in protecting against breast cancer, and therefore the importance of balancing the estradiol/estriol ratio in women using bioidentical hormone restoration therapy. See article abstract. To purchase the full article, visit the journal’s website at www.ijpc.com
“A liquid chromatography/tandem mass spectrometry method for determination of 25-hydroxy vitamin D2 and 25-hydroxy vitamin D3 in dried blood spots: a potential adjunct to diabetes and cardiometabolic risk screening.” Mark S. Newman, Theodore R Brandon, Margaret N. Groves, William L. Gregory, Sanjay Kapur, David T. Zava. Journal of Diabetes Science and Technology 2009; 3(1):156-62.
Summary: This study demonstrated an excellent correlation between levels of 25-hydroxy vitamin D2 and 25-hydroxyvitamin D3 in blood spots and serum, allowing the blood spot assay to be used for accurate assessments of vitamin D status in screening situations. Low levels of vitamin D have been linked to both type I and type II diabetes, and vitamin D deficiency is also emerging as a risk factor for cardiovascular disease. The paper discusses these implications. See the article abstract. To purchase the full article, visit the journal’s website at www.jdst.org.
“Differentiation and treatment of hypothyroidism, functional hypothyroidism and functional metabolism.” Paoletti JE. International Journal of Pharmaceutical Compounding, 2008; 12(6): 489-497.
Summary: This article looks at the different levels at which thyroid production, metabolism, and dysfunctions of utilization can lead to classical symptoms of hypothyroidism. An understanding of how to use and interpret thyroid function measurements to allow determination of where the problems exist, and how to choose appropriate treatment, is presented also. See the article abstract. To purchase the full article, visit the journal’s website at www.ijpc.com.
“Pilot study: absorption and efficacy of multiple hormones delivered in a single cream applied to the mucous membranes of the labia and vagina.” Glaser RL, Zava DT, Wurtzbacher D. Gynecologic and Obstetric Investigation 2008; 66(2):111-8.
Summary: This is the first study to document absorption of multiple hormones applied topically to the vagina by measuring their levels in both saliva and blood. Hormones included in the cream were estriol, estradiol, progesterone, DHEA, and testosterone. There was a measurable increase in health-related quality of life after using the cream in the 12 postmenopausal women involved in the study. See the article abstract. To access the full article, visit the publisher’s website.
"Cardiometabolic risk factors assessed by a finger stick dried blood spot method." Sanjay Kapur, PhD, Sonia Kapur, PhD, and David Zava, PhD. Journal of Diabetes Science and Technology 2008; 2(2): 236-241.
Summary: This article describes analytical methods for measurement of insulin, high-sensitivity C-reactive protein, and triglycerides from dried blood spots and validation of these methods by comparison with analysis performed in serum. The article shows that dried blood spot samples may be used as the sample of choice when convenience is desired and in situations where conventional blood collection is not available. See the article abstract. To access the full article, visit the journal’s website at www.jdst.org.
“Analysis of the Use of Dried Blood Spot Measurements in Disease Screening." Ramakrishnan Lakshmy, Ph.D. Journal of Diabetes Science and Technology 2008; 2(2): 242-243.
Summary: The use of dried blood spots for the measurement of insulin, high sensitivity C-reactive protein, and triglycerides is reported in this article. A good correlation between measurement of these analytes in dried blood and serum suggests that the method is valid and has the potential to be used for the screening of cardiometabolic risk factors. While this article is not a ZRT publication, it is included here because it mentions ZRT's Research Director, Sanjay Kapur, and his article listed above indicating that there is good correlation between dried capillary blood and serum obtained through venipuncture. See the article abstract. To access the full article, visit the journal’s website at www.jdst.org.
"A comparison of blood spot vs. plasma analysis of gonadotropin and ovarian steroid hormone levels in reproductive-age women." Edelman A, Stouffer R, Zava DT, Jensen JT. Fertility and Sterility 2007; 88(5): 1404-1407.
Summary: This article documents a study comparing LH, FSH, progesterone, and estradiol levels obtained from blood spot versus plasma and concludes that blood spot testing can be just as valid as blood serum testing in documenting circulating hormone levels seen during ovulatory cycles. See full article.
“Correcting misconceptions about compounding bioidentical hormones: a review of the literature.” Paoletti J. International Journal of Pharmaceutical Compounding 2007;11(4):269-272.
To purchase the full article, visit the journal’s website at www.ijpc.com.
“Saliva hormone testing.” David Zava, PhD, Townsend Letter for Doctors and Patients 2004; January:120-124.
Summary: This review discusses the rationale for, as well as advantages and disadvantages, of saliva testing. It describes and explains the phenomenon of higher saliva than serum levels of hormones when they are delivered topically, and details how salivary hormone testing can help detect hormone imbalances that affect health and wellbeing. See full article.
“A perspective on hormone replacement for women: picking up the pieces after the Women’s Health Initiative Trial.” Gillson GR, Zava DT. Part 1 – International Journal of Pharmaceutical Compounding 2003;7(4):250-256. Part II – International Journal of Pharmaceutical Compounding 2003;7(5):330-358.
To purchase the full articles, visit the journal’s website at www.ijpc.com.
“The hormonal link to breast cancer: the estrogen matrix.” Zava, DT. International Journal of Pharmaceutical Compounding 2002:6(4):250-254.
Summary: The biochemical and hormonal imbalances that increase the levels of unopposed estrogens in breast tissue, and therefore increase the risk of breast cancer, are described. Factors leading to increased risk include obesity, conventional HRT, pollutants, stress, and adrenal dysfunction. To purchase the full article, visit the journal’s website at www.ijpc.com.
“Overall self-confidence, self-confidence in mathematics, and sex-role stereotyping in relation to salivary free testosterone in university women.” Johnson W, Zava D, McCoy N. Perceptual and Motor Skills 2000; 91(2):391-401.
Summary: The relationship between salivary free testosterone levels and measures of self-confidence was studied in 40 young women. See the article abstract.
“Estrogen and progestin bioactivity of foods, herbs, and spices.” Zava DT, Dollbaum CM, Blen M. Proceedings of the Society for Experimental Biology and Medicine 1998;217(3):369-378.
Summary: This study demonstrates that various common foods, herbs, and spices contain phytoestrogens and phytoprogestins, which then exert biological activity when consumed. See the article abstract.
