Iman A Hakim

Interests

Research

Translational research on the role of bioactive food compounds such as green tea and d-limonene in modulation of oxidative damage and chronic inflammation for prevention of chronic and metabolic diseases such as cancer, cardiovascular diseases, and diabetesMy research focuses on health promotion, dietary interventions, and the role of gene-environment and gene-nutrition interactions in health promotion and chronic disease prevention.I have been the Principal Investigator of several large-scale, behavior change interventions and clinical trials focused on nutrition and cancer prevention, tea consumption and coronary heart disease, chemoprevention of lung carcinogenesis using green tea; dietary interventions to study the effects of tea consumption on smoking-related oxidative stress; role of d-limonene and citrus-cancer association in Mediterranean diet; relationship between tobacco use, oxidative damage and metabolic syndrome among current and former smokers

Teaching

Women and children health issuesGlobal Health Nutrition intervention and clinical trials Food as medicine

Courses

No activities entered.

Scholarly Contributions

Journals/Publications

• Hakim, I. A., Garland, L., Cordova, C. A., Mikhael, D. M., & Chow, H. S. (2017). Modulation of Oxidative Damage by Green and Black Tea: Role of Smoking and Gender in a Randomized Trial.. Journal of Nutrition and Food Sciences, 7(5), 1-7. doi:doi: 10.4172/2155-9600.1000633.
• Hakim, I. A., Garland, L., Harris, R., & Chow, H. S. (2018). Effects of Black and Green Tea Consumption on Blood Pressure and Liver Enzymes: A Randomized Controlled Trial.. Journal of Nutrition and Food Sciences, 8(1), 1-7. doi:doi:10.4172/2155-9600.1000661
• Al Thani, M., Leventakou, V., Sofroniou, A., Eltayeb, S. M., Sadoun, E., Hakim, I. A., Thomson, C., & Nair, U. (2021). A Telephone-Based Tobacco Cessation Program in the State of Qatar: Protocol of a Feasibility Study. International journal of environmental research and public health, 18(9).
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  In Qatar, tobacco is the leading preventable cause of death and disease. Telephone-based interventions for smoking are cost-effective and scalable interventions that are effective in promoting smoking behavior change. While many countries have implemented these services within their tobacco control programs, there is a distinct dearth of a telephone-based smoking cessation intervention that is adapted and tailored to meet the needs of people who smoke in Qatar. This study presents the protocol of a primary health care center integrated smoking quitline program in Qatar. Participants will be recruited from seven smoking clinics (recruitment sites). Trained clinic staff will provide brief advice on quitting followed by a referral to the quitline. Eligible participants (male smokers over 18 years of age) will complete baseline questionnaires and receive five weekly proactive counseling calls, an end-of-treatment assessment (approx. 1 week after Session 5), and 1- and 3-month follow-up assessments. The main aim of this study is to assess the feasibility and acceptability, which include the recruitment and retention rate, compliance to pharmacotherapy, and participant satisfaction. This is the first study to integrate an evidence-based smoking cessation intervention delivered via telephone within the healthcare system in Qatar. If effective, results can inform the development of a large-scale telephone-based program that widely reaches users of tobacco in Qatar as well as in the Middle East.
• Chebet, J. J., Ehiri, J. E., McClelland, D. J., Taren, D., & Hakim, I. A. (2021). Effect of d-limonene and its derivatives on breast cancer in human trials: a scoping review and narrative synthesis. BMC cancer, 21(1), 902.
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  D-limonene and its derivatives have demonstrated potential chemopreventive and anticancer activity in preclinical and clinical studies. The aim of this scoping review was to assess and critically appraise current literature on the effect of these bioactive citrus peel compounds on breast cancer in human trials and to identify knowledge gaps for exploration in future studies.
• Thomson, C. A., Thani, M. A., Sofroniou, A., Sadoun, E., Nair, U. S., Leventakou, V., Hakim, I. A., & Eltayeb, S. M. (2021). A Telephone-Based Tobacco Cessation Program in the State of Qatar: Protocol of a Feasibility Study.. International journal of environmental research and public health, 18(9), 4750. doi:10.3390/ijerph18094750
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  In Qatar, tobacco is the leading preventable cause of death and disease. Telephone-based interventions for smoking are cost-effective and scalable interventions that are effective in promoting smoking behavior change. While many countries have implemented these services within their tobacco control programs, there is a distinct dearth of a telephone-based smoking cessation intervention that is adapted and tailored to meet the needs of people who smoke in Qatar. This study presents the protocol of a primary health care center integrated smoking quitline program in Qatar. Participants will be recruited from seven smoking clinics (recruitment sites). Trained clinic staff will provide brief advice on quitting followed by a referral to the quitline. Eligible participants (male smokers over 18 years of age) will complete baseline questionnaires and receive five weekly proactive counseling calls, an end-of-treatment assessment (approx. 1 week after Session 5), and 1- and 3-month follow-up assessments. The main aim of this study is to assess the feasibility and acceptability, which include the recruitment and retention rate, compliance to pharmacotherapy, and participant satisfaction. This is the first study to integrate an evidence-based smoking cessation intervention delivered via telephone within the healthcare system in Qatar. If effective, results can inform the development of a large-scale telephone-based program that widely reaches users of tobacco in Qatar as well as in the Middle East.
• Thomson, C. A., Thani, M. A., Sofroniou, A., Sadoun, E., Nair, U. S., Leventakou, V., Hakim, I. A., & Eltayeb, S. M. (2021). A Telephone-Based Tobacco Cessation Program in the State of Qatar: Protocol of a Feasibility Study.. International journal of environmental research and public health, 18(9). doi:10.3390/ijerph18094750
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  In Qatar, tobacco is the leading preventable cause of death and disease. Telephone-based interventions for smoking are cost-effective and scalable interventions that are effective in promoting smoking behavior change. While many countries have implemented these services within their tobacco control programs, there is a distinct dearth of a telephone-based smoking cessation intervention that is adapted and tailored to meet the needs of people who smoke in Qatar. This study presents the protocol of a primary health care center integrated smoking quitline program in Qatar. Participants will be recruited from seven smoking clinics (recruitment sites). Trained clinic staff will provide brief advice on quitting followed by a referral to the quitline. Eligible participants (male smokers over 18 years of age) will complete baseline questionnaires and receive five weekly proactive counseling calls, an end-of-treatment assessment (approx. 1 week after Session 5), and 1- and 3-month follow-up assessments. The main aim of this study is to assess the feasibility and acceptability, which include the recruitment and retention rate, compliance to pharmacotherapy, and participant satisfaction. This is the first study to integrate an evidence-based smoking cessation intervention delivered via telephone within the healthcare system in Qatar. If effective, results can inform the development of a large-scale telephone-based program that widely reaches users of tobacco in Qatar as well as in the Middle East.
• Garcia, D. O., Morrill, K. E., Aceves, B., Valdez, L. A., Rabe, B. A., Bell, M. L., Hakim, I. A., Martinez, J. A., & Thomson, C. A. (2019). Feasibility and acceptability of a beverage intervention for Hispanic adults: results from a pilot randomized controlled trial. Public health nutrition, 22(3), 542-552.
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  To assess the feasibility and acceptability of a beverage intervention in Hispanic adults.
• Morrill, K. E., Aceves, B., Valdez, L. A., Rabe, B. A., Valdez, L. A., Thomson, C. A., Rabe, B. A., Morrill, K. E., Martinez, J. A., Hakim, I. A., Garcia, D. O., Bell, M. L., & Aceves, B. (2019). Feasibility and acceptability of a beverage intervention for Hispanic adults: results from a pilot randomized controlled trial.. Public health nutrition, 22(3), 542-552. doi:10.1017/s1368980018003051
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  To assess the feasibility and acceptability of a beverage intervention in Hispanic adults..Eligible individuals identified as Hispanic, were 18-64 years old and had BMI 30·0-50·0 kg/m2. Participants were randomized 2:2:1 to one of three beverages: Mediterranean lemonade (ML), green tea (GT) or flavoured water control (FW). After a 2-week washout period, participants were asked to consume 32 oz (946 ml) of study beverage daily for 6 weeks and avoid other sources of tea, citrus, juice and sweetened beverages; water was permissible. Fasting blood samples were collected at baseline and 8 weeks to assess primary and secondary efficacy outcomes..Tucson, AZ, USA.ParticipantsFifty-two participants were recruited over 6 months; fifty were randomized (twenty-one ML, nineteen GT, ten FW). Study population mean (sd) age 44·6 (sd 10·2) years, BMI 35·9 (4·6) kg/m2; 78 % female..Forty-four (88 %) completed the 8-week assessment. Self-reported adherence was high. No significant change (95 % CI) in total cholesterol (mg/dl) from baseline was shown -1·7 (-14·2, 10·9), -3·9 (-17·2, 9·4) and -13·2 (-30·2, 3·8) for ML, GT and FW, respectively. Mean change in HDL-cholesterol (mg/dl) -2·3 (-5·3, 0·7; ML), -1·0 (-4·2, 2·2; GT), -3·9 (-8·0, 0·2; FW) and LDL-cholesterol (mg/dl) 0·2 (-11·3, 11·8; ML), 0·5 (-11·4, 12·4; GT), -9·8 (-25·0, 5·4; FW) were also non-significant. Fasting glucose (mg/dl) increased significantly by 5·2 (2·6, 7·9; ML) and 3·3 (0·58, 6·4; GT). No significant change in HbA1c was demonstrated. Due to the small sample size, potential confounders and effect modifiers were not investigated..Recruitment and retention figures indicate that a larger-scale trial is feasible; however, favourable changes in cardiometabolic biomarkers were not demonstrated.
• Harris, R. B., Garland, L. L., Chow, H. S., Harris, R. B., Hakim, I. A., Garland, L. L., & Chow, H. S. (2018). Effects of Black and Green Tea Consumption on Blood Pressure and Liver Enzymes: A Randomized Controlled Trial. Journal of Nutrition and Food Sciences, 8(1), 1-4. doi:10.4172/2155-9600.1000661
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  Background: The effect on tea consumption on blood pressure and liver enzymes are controversial. The beneficial effects of long-term ingestion of black and green tea on systolic and diastolic blood pressure have been suggested by several studies.Objectives: The overall goal of this study was to determine the effects of high tea consumption on blood pressure and liver enzymes.Design: We completed a 6-month randomized, controlled, double-blinded trial in a group of former and current smokers who were randomized to receive black or green tea preparations or a matching placebo.Results: A total of 146 participants (80 females and 66 males) were enrolled in the study. At the end of the 6-month intervention, women in the black tea group showed a 4 mmHg decrease (p = 0.01) in systolic blood pressure while female in the green tea group showed a 30.1% decrease (p = 0.035) in Alanine transaminase (ALT). No significant changes were observed in men.Conclusion: Our data confirm previous findings related to the beneficial effect of black tea on blood pressure and of green tea on serum liver enzymes especially among females. In addition, our study showed that long-term regular consumption of black tea and green is safe.
• Morrill, K. E., Aceves, B., Valdez, L. A., Thomson, C. A., Hakim, I. A., Bell, M. L., Martinez, J. A., & Garcia, D. O. (2018). Feasibility and Acceptability of a Beverage Intervention for Hispanic Adults: A Protocol for a Pilot Randomized Controlled Trial. Nutrition Journal.
• Morrill, K. E., Aceves, B., Valdez, L. A., Thomson, C. A., Hakim, I. A., Bell, M. L., Martinez, J. A., & Garcia, D. O. (2018). Feasibility and acceptability of a beverage intervention for Hispanic adults: a protocol for a pilot randomized controlled trial. Nutrition journal, 17(1), 16.
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  In the U.S., Hispanics have among the highest rates of overweight and obesity when compared to other racial/ethnic groups placing them at a greater risk for obesity-related disease. Identifying intervention strategies to reduce caloric intake and/or improve cardiometabolic health in Hispanics is critical to reducing morbidity and mortality among this large and growing population. Evidence exists to support diet-specific behavioral interventions, including beverage modifications, in reducing obesity-related health risks. However, the acceptability and feasibility of a beverage intervention in obese Hispanic adults has not been robustly evaluated.
• Morrill, K. E., Aceves, B., Valdez, L. A., Valdez, L. A., Thomson, C. A., Morrill, K. E., Martinez, J. A., Hakim, I. A., Garcia, D. O., Bell, M. L., & Aceves, B. (2018). Feasibility and acceptability of a beverage intervention for Hispanic adults: a protocol for a pilot randomized controlled trial.. Nutrition journal, 17(1), 16. doi:10.1186/s12937-018-0329-y
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  In the U.S., Hispanics have among the highest rates of overweight and obesity when compared to other racial/ethnic groups placing them at a greater risk for obesity-related disease. Identifying intervention strategies to reduce caloric intake and/or improve cardiometabolic health in Hispanics is critical to reducing morbidity and mortality among this large and growing population. Evidence exists to support diet-specific behavioral interventions, including beverage modifications, in reducing obesity-related health risks. However, the acceptability and feasibility of a beverage intervention in obese Hispanic adults has not been robustly evaluated..The objective of this pilot study is to assess the feasibility and acceptability of a randomized, controlled beverage intervention in 50 obese Hispanic adults ages 18-64 over 8-weeks. Eligible participants were obese (30-50.0 kg/m2), between the ages 18-64, self-identified as Hispanic, and were able to speak, read, and write in either English and/or Spanish. Study recruitment was completed August 2017. Upon the completion of baseline assessments, participants will be randomized to either Mediterranean lemonade, Green Tea, or flavored water control. After completing a 2-week washout period, participants will be asked to consume 32 oz. per day of study beverage for 6-weeks while avoiding all other sources of tea, lemonade, citrus, juice, and other sweetened beverages; water is permissible. Primary outcomes will be recruitment, retention, and acceptability of the intervention strategies. Our study will also evaluate participant-reported tolerance and as an exploratory aim, assess safety/toxicity-related to renal and/or liver function. Fasting blood samples will be collected at baseline and 8-weeks to assess the primary efficacy outcomes: total cholesterol, high-density lipoprotein (HDL), and low-density lipoprotein (LDL). Secondary outcomes include fasting glucose, hemoglobin A1c (HbA1c), and high-sensitivity C-reactive protein (hs-CRP)..This pilot study will provide important feasibility, safety, and early efficacy data necessary to design a larger, adequately-powered randomized controlled trial..NCT02911753 ( ClinicalTrials.gov ). Registered September 19, 2016. Last updated November 1, 2017.
• Chow, H. S., Hakim, I. A., Foote, J. A., Chow, H. S., & Aldaham, S. A. (2017). Abstract B14: Modulating effects of green and black tea on biomarkers of chronic inflammation by gender and smoking status. Cancer Epidemiology and Prevention Biomarkers, 26. doi:10.1158/1538-7755.carisk16-b14
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  Background/Purpose: Epidemiologic data implies that there are gender differences in lung cancer pathogenesis and possibly increased susceptibility to lung cancer in women. Chronic inflammation has been implicated as important modulator of human health by playing a significant role in both disease prevention and disease development. Several studies have demonstrated increased interleukin 6 (IL-6) and C-reactive protein (CRP) in the blood of smokers. The overall goal of this study was to develop a feasible tea intervention that will serve as a model for the chemoprevention of a wide range of tobacco-related diseases. Our immediate goal, that was addressed over a 4-year study period, was to determine the effects of high tea consumption on biological markers of chronic inflammation that mediate lung cancer risk, including, IL-6, CRP and antioxidant enzyme activities. Methods: We completed a 6-month randomized, controlled, double-blinded trial in a group of current and former smokers. Participants were stratified on smoking status and gender, and were randomized to green or black tea preparations or a control intervention (matching placebo). Levels of urinary iIL-6 and CRP are used to measure chronic inflammation and levels of superoxide dismutase (SOD) in red blood cells are used to measure antioxidant enzymes. Results: The study protocol was approved by all parties. A total of 138 participants (78 females and 60 males) completed the study. Our data show that il6 is significantly correlated with years of smoking and pack/year among smokers and former smokers. At the end of the 6-month intervention, female smokers in the green tea group showed a significant decrease in IL-6 (P=0.036) while male former smokers in the black tea group showed a significant decrease in CRP levels (P=0.012). There were no significant changes in dietary and serum antioxidant levels between the different groups. Conclusion: This data implies that smokers are more likely to benefit from green tea intake while the beneficial effects of black tea are observed among former smokers. Note: This abstract was not presented at the conference. Citation Format: Iman A. Hakim, Sami A. Aldaham, Janet Foote, H-H Sherry Chow. Modulating effects of green and black tea on biomarkers of chronic inflammation by gender and smoking status. [abstract]. In: Proceedings of the AACR Special Conference: Improving Cancer Risk Prediction for Prevention and Early Detection; Nov 16-19, 2016; Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(5 Suppl):Abstract nr B14.
• Garcia, D. O., Martinez, J. A., Bell, M. L., Hakim, I. A., Thomson, C. A., Valdez, L. A., Aceves, B., & Morrill, K. E. (2017). Feasibility and Acceptability of a Beverage Intervention for Hispanic Adults: A Protocol for a Pilot Randomized Controlled Trial. Nutrition Journal.
• Harris, R. B., R, H., L, G., Ia, H., Hhs, C., Harris, R. B., Hakim, I. A., Garl, G., Dm, M., & Ca, C. (2017). Modulation of Oxidative Damage by Green and Black Tea: Role of Smokingand Gender in a Randomized Trial. Journal of Nutrition and Food Sciences, 7(5), 1-5. doi:10.4172/2155-9600.1000633
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  Background: Oxidative stress has been implicated as an important modulator of human health and can play a role in both disease prevention and disease development. Objectives: The overall goal of this study was to determine the effects of high tea consumption on biological markers of oxidative stress that mediate lung cancer risk, including, 8-hydroxydeoxy-guanosine (8-OHdG) and F2-isoprostanes (8-iso-PGF2α). Design: We completed a 6-month randomized, controlled, double-blinded trial in a group of former and current smokers who were randomized to receive green or black tea preparations or a matching placebo. Results: A total of 146 participants (80 females and 66 males) completed the study. At the end of the 6-month intervention, female smokers in the green tea group showed a 35% decrease (p=0.04) in DNA damage while female former smokers in the black tea group showed a 26% decrease (p=0.015) in lipid damage. No significant changes in markers of oxidative stress were observed in men. Conclusion: This data confirm our previous findings related to the beneficial effect of green tea on oxidative DNA damage among female smokers. The significant beneficial effect of black tea on oxidative lipid damage as well as the gender difference merit further studies.
• Hakim, I. A. (2016). Potential role of d-limonene in breast cancer prevention. Journal of Nutrition and Food Sciences, 06(08). doi:10.4172/2155-9600.c1.034
• Aldaham, S., Foote, J. A., Chow, H. S., & Hakim, I. A. (2015). Smoking Status Effect on Inflammatory Markers in a Randomized Trial of Current and Former Heavy Smokers. International journal of inflammation, 2015, 439396.
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  Background. The level of systemic inflammation as measured by circulating levels of C-reactive protein (CRP) and interleukin-6 (IL-6) is linked to an increased risk for cardiovascular diseases (CVD) and cancer. Methods. We recruited 154 current and former smokers between 40 and 80 years of age with 25 or more pack-years of smoking history to study the relationship between inflammatory markers (CRP and IL-6) and smoking status. Results. Our results show that male smokers had significantly higher levels of serum IL-6 compared to male former smokers. We did not find any gender specific differences for smoking and CRP levels but the IL-6 levels were slightly lower in females compared to males. Additionally, our results show that CRP is significantly associated with IL-6 regardless of smoking status. Modelling indicates that the significant predictors of CRP levels were biomarkers of the metabolic syndrome while the significant predictors of IL-6 levels were age and plasma triglycerides among former smokers and the numbers of smoked packs of cigarettes per year among smokers. Conclusions. In conclusion, our study showed that CRP levels were not associated with markers of smoking intensity. However, IL-6 levels were significantly associated with smoking especially among current smokers.
• Miller, J. A., Thompson, P. A., Hakim, I. A., Lopez, A. M., Thomson, C. A., Hsu, C., & Chow, H. S. (2013). Expression of epidermal growth factor, transforming growth factor-β1 and adiponectin in nipple aspirate fluid and plasma of pre and post-menopausal women. Biomarker research, 1(1).
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  Nipple aspirate fluid (NAF) contains large amounts of protein thought to reflect the microenvironment of the breast, and is of interest in breast cancer prevention research. The correlation between specific NAF proteins to plasma concentrations have not been well studied in healthy women. We collected matched NAF and plasma from 43 healthy pre and postmenopausal women participating in an early phase clinical study to compare the levels of putative cancer protein biomarkers. We compared baseline NAF and plasma levels of epidermal growth factor (EGF), transforming growth factor-beta 1 (TGF-β1), and adiponectin and evaluated menopausal status and body mass index (BMI) as potential modifying factors.
• Yousef, F. M., Jacobs, E. T., Kang, P. T., Hakim, I. A., Going, S., Yousef, J. M., Al-Raddadi, R. M., Kumosani, T. A., & Thomson, C. A. (2013). Vitamin D status and breast cancer in Saudi Arabian women: case-control study. The American journal of clinical nutrition, 98(1).
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  The role of vitamin D in breast cancer prevention is equivocal. Saudi Arabian women may be at greater risk of vitamin D deficiency because of a darker skin type and a greater likelihood of reduced ultraviolet B radiation exposure. Data regarding the vitamin D status of Saudi Arabian women and its relation to breast cancer risk are lacking.
• Hakim, I. A., Harris, R., Garland, L., Cordova, C. A., Mikhael, D. M., & Sherry Chow, H. (2012). Gender difference in systemic oxidative stress and antioxidant capacity in current and former heavy smokers. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 21(12).
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  Several studies suggested that women may be more susceptible to oxidative damage induced by cigarette smoking, but the role of smoking status and antioxidant capacity in gender difference in susceptibility to oxidative damage has not been well studied.
• Miller, J. A., Thompson, P. A., Hakim, I. A., Lopez, A. M., Thomson, C. A., Chew, W., Hsu, C., & Chow, H. S. (2012). Safety and Feasibility of Topical Application of Limonene as a Massage Oil to the Breast. Journal of cancer therapy, 3(5A).
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  Limonene, a major component in citrus oil, has demonstrated anti-cancer effects in preclinical mammary cancer models. However, the effective oral dose translates to a human dose that may not be feasible for chronic dosing. We proposed to evaluate topical application of limonene to the breast as an alternative dosing strategy.
• Chow, H. S., & Hakim, I. A. (2011). Pharmacokinetic and chemoprevention studies on tea in humans. Pharmacological research : the official journal of the Italian Pharmacological Society, 64(2).
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  Green tea and its major polyphenols constituents, tea catechins, have been shown to have many health benefits including cancer prevention. Tea catechins and tea catechin metabolites/catabolites are bioavailable in the systemic circulation after oral intake of green tea or green tea catechins. The metabolites/catabolites identified in humans include glucuronide/sulfate conjugates, methylated tea catechin conjugates, and microflora-mediated ring fission products and phenolic acid catabolites. Plasma levels of unchanged tea catechins in humans are mostly in the sub-μM or nM concentration range, which is much lower than the effective concentrations determined in most in vitro studies. However, some of the catechin metabolites/catabolites are present in the systemic circulation at levels much higher than those of the parent catechins. The contribution of catechin derived metabolites/catabolites to the biological effects associated with green tea is yet to be defined. A limited number of chemoprevention trials of green tea or green tea catechins have been conducted to date and have observed potential preventive activity for oral, prostate, and colorectal cancer. Emerging data from multiple ongoing intervention trials will further contribute to defining the cancer preventive activity of green tea or green tea catechins.
• Jessica A. Miller, ., Patricia A. Thompson, ., Iman A. Hakim, ., H.-H. Sherry Chow, ., & Cynthia A. Thomson, . (2011). D-Limonene: A bioactive food component from citrus and evidence for a potential role in breast cancer prevention and treatment. Oncology Reviews, 5(1), 31-42.
• Miller, J. A., Chow, H. S., Vining, D. R., Thomson, P., Miller, J. A., Lopez, A. M., Hakim, I. A., Chow, H. S., & Chew, W. M. (2010). Abstract A79: Human breast tissue bioavailability of topically applied limonene. Cancer Prevention Research, 3. doi:10.1158/1940-6207.prev-09-a79
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  Purpose: Limonene is a monocyclic monoterpene found at high concentration in citrus peel oil and has demonstrated anti‐cancer effects in preclinical studies of mammary carcinogenesis. However, the effective oral dose determined in rodents extrapolates to a human dose that may not be feasible for long‐term consumption. Limonene is highly lipophilic and has been long explored as an enhancer for percutaneous absorption of pharmaceutical drugs, including tamoxifen. Preliminary work from our group demonstrated that topically applied limonene is absorbed through the mouse skin and accumulates in the mammary glands. Methods: We conducted a pilot clinical study to determine whether limonene would be bioavailable in the breast following topical application. In the first study phase, we recruited 19 healthy women to apply limonene containing massage oil to the breast daily or 3x/wk. Nipple aspirate fluid (NAF) and plasma samples were collected before and after 4 weeks of limonene massage application. Sample limonene concentrations were determined using gas chromatography‐mass spectrometry. In the second study phase, we recruited 25 healthy women to undergo 4 weeks of daily limonene massage oil application to the breast. Potential agent effect biomarkers were determined in NAF and plasma collected before and after the limonene massage application. Results: In samples collected from the first study phase, no significant increase in NAF and plasma limonene levels was observed following the limonene massage application, possibly because limonene deposits in the fatty breast tissue with minimal secretion to NAF or systemic circulation. Changes in agent effect biomarkers in NAF, including TGF‐beta, EGF, and adiponectin, were evaluated in the second study phase for determination of the breast tissue limonene bioavailability. There were no consistent changes in the agent effect biomarkers overall or in pre‐menopausal women following the limonene massage application. However, among the post‐menopausal women (n =8), there were significant increases in NAF levels of TGF‐beta (p = 0.005) and EGF (p = 0.032), and there was an increasing trend in adiponectin (p = 0.164, n=5 due to limited NAF volume). Conclusions: We conclude that breast massage application of limonene containing massage oil did not result in consistent changes in limonene secretion to the NAF and the potential drug effect biomarkers in NAF. However, limonene massage application increased the NAF expression of TGF‐beta and EGF in post‐menopausal women, indicative of the intervention effects in the breast tissue. Further studies are needed to explore the potential effects of topical limonene massage intervention on carcinogenesis biomarkers in a larger cohort of post‐menopausal women. Supported by Department of Defense, BCRP Idea Award, BC061529 Citation Information: Cancer Prev Res 2010;3(1 Suppl):A79.
• Miller, J. A., Hakim, I. A., Chew, W., Thompson, P., Thomson, C. A., & Chow, H. S. (2010). Adipose tissue accumulation of d-limonene with the consumption of a lemonade preparation rich in d-limonene content. Nutrition and cancer, 62(6), 783-8.
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  d-limonene is a bioactive food component found in high concentration in citrus peel oil with anticancer effects in preclinical studies of mammary carcinogenesis. Extrapolation of preclinical data to human cancer is limited, in part, by inadequate information on the oral bioavailability and tissue disposition of d-limonene in humans. As a fat-soluble compound, d-limonene is more likely to deposit in fatty tissues such as the breast. To assess disposition of d-limonene in humans, we conducted a pilot study of oral d-limonene-rich lemonade. Following a 1-wk washout period devoid of citrus, healthy adults consumed 40 oz. of freshly prepared lemonade containing 500 to 600 mg d-limonene daily for 4 wk. On the first and last consumption days, blood and buttock fat biopsy were collected. Matched preintervention and postintervention fat biopsies (n = 7), and matched preintervention and postintervention plasma samples (n = 6), were analyzed for d-limonene levels using gas chromatography and mass spectrometry. There was a significant increase in d-limonene levels in the fat biopsies after 4 wk (P = 0.009); initial levels ranged from nondetectable to 7.79 micromol/kg tissue, and postintervention levels ranged from 53.6 to 294 micromol/kg tissue. Plasma d-limonene levels increased from 0.35 to 0.72 micromol/l initially to postintervention levels of 0.54 to 1.65 micromol/l (P = 0.016). Postintervention adipose d-limonene levels were 51.0 to 195 times higher than plasma levels (P = 0.009). Our results demonstrate accumulation of d-limonene in adipose tissue after oral dosing and support additional studies of d-limonene for chemoprevention in tissues such as the breast that are comprised of a significant fat fraction.
• Stendell-Hollis, N. R., Thomson, C. A., Thompson, P. A., Bea, J. W., Cussler, E. C., & Hakim, I. A. (2010). Green tea improves metabolic biomarkers, not weight or body composition: a pilot study in overweight breast cancer survivors. Journal of human nutrition and dietetics : the official journal of the British Dietetic Association, 23(6), 590-600.
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  Overweight status after breast cancer treatment may increase a woman's risk for recurrent disease and/or early onset cardiovascular disease. Green tea has been proposed to promote weight loss and favourably modify glucose, insulin and blood lipids. This pilot study tested the effect of daily decaffeinated green tea consumption for 6 months on weight and body composition, select metabolic parameters and lipid profiles in overweight breast cancer survivors.
• Alsaif, M. A., Alhamdan, A. A., Alothman, A. M., Al-Mummar, M., Al-Attas, O., Hakim, I. A., Harris, R., & Lei, D. (2008). Variations between diagnosed and undiagnosed Saudi diabetics. The new Egyptian Journal of Medicine, 38(3), 131-141.
• Hakim, I. A., Chow, H. S., & Harris, R. B. (2008). Green tea consumption is associated with decreased DNA damage among GSTM1-positive smokers regardless of their hOGG1 genotype. The Journal of nutrition, 138(8), 1567S-1571S.
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  The levels of tobacco-related DNA adducts in human tissues reflect a dynamic process that is dependent on the intensity and time of exposure to tobacco smoke, the metabolic balance between activation of detoxification mechanisms, and the removal of adducts by DNA repair and/or cell turnover. Urinary 8-hydroxydeoxyguanosine (8-OHdG) is probably 1 of the most abundant DNA lesions formed during oxidative stress and is proposed as a sensitive biomarker of the overall oxidative DNA damage and repair. We performed this study to determine whether there were differences in increased oxidative stress susceptibility to smoking within the combined GSTM1 and hOGG1 genotypes and the impact of green tea drinking on this. We completed a Phase II randomized, controlled, 3-arm tea intervention trial to study the effect of high consumption of decaffeinated green or black tea or water on urinary 8-OHdG among heavy smokers and to evaluate the roles of GSTM1 and hOGG1 genotypes as effect modifiers. Assessment of urinary 8-OHdG after adjustment for baseline measurements and other potential confounders revealed a significant effect of green tea consumption (P = 0.001). The change from baseline was significant in all GSTM1-positive smokers regardless of their hOGG1 genotype. Our data show that consumption of 4 cups (960 mL) of tea/d is a feasible and safe approach and was associated with a significant decrease in urinary 8-OHdG among green tea consumers. Our finding also suggests that green tea intervention might be effective in decreasing DNA damage in the subgroup of smokers who are GSTM1 positive regardless of their hOGG1 genotype.
• Miller, J. A., Chow, H. S., Thomson, C. A., Thompson, P. A., Miller, J. A., Hakim, I. A., Chow, H. S., & Chew, W. (2008). Abstract B125: Adipose tissue accumulation of d-limonene with the consumption of a lemonade preparation rich in d-limonene content.. Cancer Prevention Research, 1. doi:10.1158/1940-6207.prev-08-b125
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  B125 Purpose d-Limonene is a bioactive food component commonly found in high concentration in citrus peel. It has demonstrated anti-cancer effects in preclinical studies with the most compelling results in mammary carcinogenesis models. Information on the oral bioavailability and tissue disposition of d-limonene in humans is rather limited for extrapolation of preclinical data to human situations. As a fat-soluble compound, d-limonene is more likely to deposit in fatty tissues such as the breast where we hypothesize that biologic activity may be greatest. We conducted a clinical study to determine the systemic and adipose tissue disposition of d-limonene with the consumption of a lemonade preparation rich in d-limonene content. Methods Seven healthy adults underwent a one-week washout period during which their diets were void of all citrus. At entry, participants consumed a breakfast that included the freshly prepared lemonade (40 oz containing 0.6 gm d-limonene) in the clinic. Serum and needle fat biopsies of the buttocks were collected 6 hours post-feeding. Participants then consumed 40 oz of freshly prepared lemonade daily for 4 weeks. At completion of the 4-week feeding period, participants repeated the controlled breakfast with high d-limonene lemonade prepared in the clinic followed by repeat serum and fat sampling. Matched pre- and post-intervention fat biopsies (n = 7) and serum samples (n = 6) were analyzed for d-limonene levels using gas chromatography-mass spectrometry. Results The d-limonene levels in the initial fat biopsies ranged from non-detectable to 0.79 μM (median = 2.55 μM) concentration. The adipose d-limonene levels increased significantly (p Conclusions Oral consumption of high d-limonene lemonade results in d-limonene deposition in adipose tissue in levels much higher than levels in the systemic circulation. Assessing the serum d-limonene levels is not likely to reflect d-limonene exposure in the adipose tissue. In addition, given d-limonene’s anticarcinogenic properties, and because breast tissue is mostly composed of adipose, the data suggests that d-limonene could also accumulate at this site, thus potentially modulating breast cancer risk. Citation Information: Cancer Prev Res 2008;1(7 Suppl):B125.
• Miller, J. A., Hakim, I. A., Thomson, C., Thompson, P., & Chow, H. S. (2008). Determination of d-limonene in adipose tissue by gas chromatography-mass spectrometry. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, 870(1), 68-73.
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  We developed a novel method for analyzing d-limonene levels in adipose tissue. Fat samples were subjected to saponification followed by solvent extraction. d-Limonene in the sample extract was analyzed using gas chromatography-mass spectrometry (GC-MS) with selected ion monitoring. Linear calibration curves were established over the mass range of 79.0-2529 ng d-limonene per 0.1g of adipose tissue. Satisfactory within-day precision (R.S.D. 6.7-9.6%) and accuracy (%difference of -2.7 to 3.8%) and between-day precision (R.S.D. 6.0-10.7%) and accuracy (%difference of 1.8-2.6%) were achieved. The assay was successfully applied to human fat biopsy samples from a d-limonene feeding trial.
• Chow, H. S., Hakim, I. A., Vining, D. R., Crowell, J. A., Tome, M. E., Ranger-Moore, J., Cordova, C. A., Mikhael, D. M., Briehl, M. M., & Alberts, D. S. (2007). Modulation of human glutathione s-transferases by polyphenon e intervention. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 16(8), 1662-6.
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  Green tea consumption has been associated with decreased risk of certain types of cancers in humans. Induction of detoxification enzymes has been suggested as one of the biochemical mechanisms responsible for the cancer-preventive effect of green tea. We conducted this clinical study to determine the effect of repeated green tea polyphenol administration on a major group of detoxification enzymes, glutathione S-transferases (GST).
• Thomson, C. A., Newton, T. R., Graver, E. J., Jackson, K. A., Reid, P. M., Hartz, V. L., Cussler, E. C., & Hakim, I. A. (2007). Cruciferous vegetable intake questionnaire improves cruciferous vegetable intake estimates. Journal of the American Dietetic Association, 107(4), 631-43.
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  To develop a validated, focused Cruciferous Vegetable Food Frequency Questionnaire (FFQ) as an assessment tool for specific quantification of dietary cruciferous vegetable exposure.
• Chow, H. S., Hakim, I. A., Vining, D. R., Crowell, J. A., Cordova, C. A., Chew, W. M., Xu, M., Hsu, C., Ranger-Moore, J., & Alberts, D. S. (2006). Effects of repeated green tea catechin administration on human cytochrome P450 activity. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 15(12), 2473-6.
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  Preclinical studies suggested that green tea or green tea catechins can modulate the activities of drug-metabolizing enzymes. We conducted this clinical study to determine the effect of repeated green tea catechin administration on human cytochrome P450 (CYP) enzyme activities.
• Chow, H. S., Vining, D. R., Ranger-moore, J., Mikhael, D. M., Hakim, I. A., Crowell, J. A., Cordova, C. A., Chow, H. S., & Alberts, D. S. (2006). Effects of green tea catechin intervention on human Phase II detoxification enzymes.. Cancer Epidemiology and Prevention Biomarkers, 15.
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  Fifth AACR International Conference on Frontiers in Cancer Prevention Research, Nov 12-15, 2006 B152 Purpose: Green tea consumption has been associated with decreased risk of certain types of cancers in humans. Modulation of carcinogen activation and detoxification enzymes has been suggested as one of the biochemical mechanisms responsible for the cancer preventive effect of green tea. We conducted this clinical study to determine the effect of repeated green tea catechin administration on human Phase II detoxification enzymes. Methods: Forty-two healthy volunteers underwent a 4-week washout period by refraining from tea or tea related products. At the end of the washout period, a fasting blood sample was collected, and serum and lymphocytes were isolated for assessment of glutathione S-transferase (GST) activity and level. Following the baseline evaluation, study participants underwent 4 weeks of green tea catechin intervention at a dose that contains 800 mg epigallocatechin gallate once a day. Upon completion of the green tea catechin intervention, a fasting blood sample was collected and serum and lymphocytes isolated for post-intervention GST assessment. Serum total bilirubin levels were analyzed before and after repeated green tea catechin administration as a surrogate measurement of UDP-glucuronosyltransferase (UGT) 1A1 enzyme activity. Results: Four weeks of green tea catechin intervention significantly enhanced the GST activity and GST-π levels in peripheral blood lymphocytes in individuals with baseline activity or level in the lowest tertile. Repeated green tea catechin administration had minimal effects on plasma GST-α level. Furthermore, green tea catechin intervention significantly lowered serum bilirubin levels, implicating an induction of UGT1A1 activity, in individuals with baseline bilirubin levels in the highest tertile. Conclusions: We conclude that repeated green tea catechin administration induced GST and UGT1A1 activity in individuals with low baseline enzyme activity. This suggests that green tea catechin intervention would enhance the detoxification of carcinogens in individuals with low baseline detoxification capacity.
• Chow, H. S., Hakim, I. A., Vining, D. R., Crowell, J. A., Ranger-Moore, J., Chew, W. M., Celaya, C. A., Rodney, S. R., Hara, Y., & Alberts, D. S. (2005). Effects of dosing condition on the oral bioavailability of green tea catechins after single-dose administration of Polyphenon E in healthy individuals. Clinical cancer research : an official journal of the American Association for Cancer Research, 11(12), 4627-33.
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  Green tea has been shown to exhibit cancer-preventive activities in preclinical studies. Its consumption has been associated with decreased risk of certain types of cancers in humans. The oral bioavailability of the major green tea constituents, green tea catechins, is low, resulting in systemic catechin levels in humans many fold less than the effective concentrations determined in in vitro systems. We conducted this clinical study to test the hypothesis that the oral bioavailability of green tea catechins can be enhanced when consumed in the absence of food.
• Harris, R. B., Foote, J. A., Hakim, I. A., Bronson, D. L., & Alberts, D. S. (2005). Fatty acid composition of red blood cell membranes and risk of squamous cell carcinoma of the skin. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 14(4), 906-12.
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  Differential effects of fatty acids on carcinogenesis suggest that fatty acid composition is important in tumor development. Arachidonic acid and its metabolites elicit inflammation and promote tumor formation in mouse skin. Inhibitors of the arachidonic cascade inhibit tumor incidence. A population-based case control study in Southeastern Arizona tested the hypothesis that lower levels of arachidonic acid in RBC membranes were associated with decreased risk of skin squamous cell carcinoma (SCC; n = 335 SCC cases and 321 controls). Extracted and esterified RBC fatty acids were analyzed using capillary gas chromatography. Individual peaks for 14 fatty acids were measured as a percentage of total fatty acids. Logistic regression was used to estimate odds ratios (OR), adjusting for SCC risk factors (age, gender, actinic keratosis history, freckling, and tanning ability). Increased levels of arachidonic acid in RBC membranes were associated with increased risk of SCC [odds ratio (OR), 1.08 per mg/100 mL change; 95% confidence interval (95% CI), 1.02-1.15] and this association remained when controls with actinic keratosis precursor lesions were excluded. SCC risk was highest among the upper quartile of arachidonic acid (OR, 2.38; 95% CI, 1.37-4.12). In contrast, increasing proportions of palmitic acid (OR, 0.94; 95% CI, 0.89-1.00) and palmitoleicacid (OR, 0.49; 95% CI, 0.30-0.81) were associated with reduced SCC risk. More studies are needed to elucidate the function of RBC fatty acids so that recommendations can be made to alter the human diet for cancer prevention.
• Harris, R. B., Tommasino, M., Nielson, C. M., Harris, R. B., Hakim, I. A., Giuliano, A. R., & Franceschi, S. (2005). 084: Human Papillomavirus and Cutaneous Squamous Cell Carcinoma: A Case-Control Study. American Journal of Epidemiology, 161(Supplement_1), S21-S21. doi:10.1093/aje/161.supplement_1.s21c
• Thomson, C. A., Giuliano, A. R., Shaw, J. W., Rock, C. L., Ritenbaugh, C. K., Hakim, I. A., Hollenbach, K. A., Alberts, D. S., & Pierce, J. P. (2005). Diet and biomarkers of oxidative damage in women previously treated for breast cancer. Nutrition and cancer, 51(2), 146-54.
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  This study sought to evaluate the relationship between dietary intake of fat, polyunsaturated fat, saturated fat, arachidonic acid, and selected dietary antioxidants and levels of oxidative damage as measured by urinary levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-epi-prostaglandin F2alpha (8-iso-PGF2alpha) in women previously treated for breast cancer. Two hundred two study subjects participating in the Women's Healthy Eating and Living (WHEL) study were included in this ancillary study. Dietary intakes and concentrations of urinary 8-OHdG and 8-iso-PGF2alpha were measured at baseline and 12 mo in the 179 women included in the analytical cohort. Study subjects demonstrated a significant reduction in dietary total, polyunsaturated, and saturated fat intake and a significant increase in vitamins E and C and beta-carotene intake from baseline to 12 mo. Linear mixed-models analysis using baseline and Year 1 data indicated that vitamin E intake was inversely associated with both 8-OHdG and 8-iso-PGF2alpha. 8-Iso-PGF2alpha is increased with increased body mass index (BMI) and polyunsaturated fatty acid (PUFA) intake, indicating an increase in lipid peroxidation with greater BMI and higher PUFA intake. 8-OHdG was inversely related to age but positively related to arachidonic acid, indicating an increase in DNA damage with higher intake of arachidonic acid (meat). The results of this nested case-controlled study provide potential mechanisms by which a high fruit and vegetable, low-fat diet might reduce the recurrence rate of or early-stage breast cancer.
• Thomson, C. A., Harris, R. B., Craft, N. E., & Hakim, I. A. (2005). A cross-sectional analysis demonstrated the healthy volunteer effect in smokers. Journal of clinical epidemiology, 58(4), 378-82.
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  This cross-sectional descriptive analysis sought to determine if a healthy volunteer effect can be demonstrated among smokers selected to participate in a dietary intervention trial.
• Boseila, S. A., Gabr, A. A., & Hakim, I. A. (2004). Blood lead levels in Egyptian children: influence of social and environmental factors. American journal of public health, 94(1), 47-9.
• Hakim, I. A., Chow, H. S., Harris, R., Dean, M., & Ali, I. U. (2004). hOGG1 Genotype, Green Tea, and Oxidative DNA Damage Among Heavy Smokers. Evidence-Based Integrative Medicine, 1(4), 245-251.
• Hakim, I. A., Dean, M., Harris, R. B., & Ali, I. U. (2004). Effect of a 4-Month Tea Intervention on Oxidative DNA Damage among Heavy Smokers: Role of XRCC1 Genotypes. Evidence Based Preventive Medicine, 1(2), 93-99.
• Hakim, I. A., Harris, R. B., Chow, H. S., Dean, M., Brown, S., & Ali, I. U. (2004). Effect of a 4-month tea intervention on oxidative DNA damage among heavy smokers: role of glutathione S-transferase genotypes. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 13(2), 242-9.
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  Glutathione S-transferase (GST), a member of the phase II group of xenobiotic metabolizing enzymes, has been intensively studied at the levels of phenotype and genotype. The GST mu 1 (GSTM1) and GST theta 1 (GSTT1) genes have a null-allele variant in which the entire gene is absent. The null genotype for both enzymes has been associated with many different types of tumors. The aim of this study was to determine the possible differences in increased oxidative stress susceptibility to smoking within the GSTM1 and GSTT1 genotypes and the impact of high tea drinking on this. We designed a Phase II randomized, controlled, three-arm tea intervention trial to study the effect of high consumption (4 cups/day) of decaffeinated green or black tea, or water on oxidative DNA damage, as measured by urinary 8-hydroxydeoxyguanosine (8-OHdG), among heavy smokers over a 4-month period and to evaluate the roles of GSTM1 and GSTT1 genotypes as effect modifiers. A total of 133 heavy smokers (100 females and 33 males) completed the intervention. GSTM1 and GSTT1 genotype statuses were determined with a PCR-based approach. Multiple linear regression models were used to estimate the main effects and interaction effect of green and black tea consumption on creatinine-adjusted urinary 8-OHdG, with or without adjustment for potential confounders. Finally, we studied whether the effect of treatment varied by GSTM1 and GSTT1 status of the individual. Although there were no differences in urinary 8-OHdG between the groups at baseline, the between-group 8-OHdG levels at month 4 were statistically significant for GSTM1-positive smokers (P = 0.05) and GSTT1-positive smokers (P = 0.02). GSTM1-positive and GSTT1-positive smokers consuming green tea showed a decrease in urinary 8-OHdG levels after 4 months. Assessment of urinary 8-OHdG after adjustment for baseline measurements and other potential confounders revealed significant effect for green tea consumption (P = 0.001). The change from baseline was significant in both GSTM1-positive (t = -2.99; P = 0.006) and GSTT1-positive (P = 0.004) green tea groups, but not in the GSTM1-negative (P = 0.07) or GSTT1-negative (P = 0.909) green tea groups. Decaffeinated black tea consumption had no effect on urinary 8-OHdG levels among heavy smokers. Our data show that consumption of 4 cups of tea/day is a feasible and safe approach and is associated with a significant decrease in urinary 8-OHdG among green tea consumers after 4 months of consumption. This finding also suggests that green tea intervention may be effective in the subgroup of smokers who are GSTM1 and/or GSTT1 positive.
• Chen, Z., Pettinger, M. B., Ritenbaugh, C., LaCroix, A. Z., Robbins, J., Caan, B. J., Barad, D. H., & Hakim, I. A. (2003). Habitual tea consumption and risk of osteoporosis: a prospective study in the women's health initiative observational cohort. American journal of epidemiology, 158(8), 772-81.
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  The purpose of this study was to prospectively investigate associations of habitual drinking of regular tea with bone mineral density and fracture risk. Study participants were a multiethnic postmenopausal cohort (n = 91,465) from the nationwide Women's Health Initiative Observational Study. These women were recruited in the United States and aged 50-79 years at the time of enrollment (1994-1998). The average follow-up time was 4.1 years. Habitual consumption of regular tea was assessed with a structured questionnaire at baseline. Clinical fractures during the follow-up were reported in questionnaires, and hip fractures were further confirmed by reviewing medical records. Bone mineral density measurements were conducted among a subgroup of women (n = 4,979) at three Women's Health Initiative bone mineral density centers using dual-energy x-ray absorptiometry. Multivariate analyses suggested a positive trend of increased total body bone mineral density with tea drinking (p < 0.05). However, results from the Cox proportional hazard models did not show any significant association between tea drinking and the risk of fractures at the hip and forearm/wrist. In conclusion, the results from this study indicate that the effect of habitual tea drinking on bone density is small and does not significantly alter the risk of fractures among the US postmenopausal population.
• Chow, H. S., Cai, Y., Hakim, I. A., Crowell, J. A., Shahi, F., Brooks, C. A., Dorr, R. T., Hara, Y., & Alberts, D. S. (2003). Pharmacokinetics and safety of green tea polyphenols after multiple-dose administration of epigallocatechin gallate and polyphenon E in healthy individuals. Clinical cancer research : an official journal of the American Association for Cancer Research, 9(9), 3312-9.
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  Green tea and green tea polyphenols have been shown to possess cancer preventive activities in preclinical model systems. In preparation for future green tea intervention trials, we have conducted a clinical study to determine the safety and pharmacokinetics of green tea polyphenols after 4 weeks of daily p.o. administration of epigallocatechin gallate (EGCG) or Polyphenon E (a defined, decaffeinated green tea polyphenol mixture). In an exploratory fashion, we have also determined the effect of chronic green tea polyphenol administration on UV-induced erythema response.
• Hakim, I. A., Alsaif, M. A., Alduwaihy, M., Al-Rubeaan, K., Al-Nuaim, A. R., & Al-Attas, O. S. (2003). Tea consumption and the prevalence of coronary heart disease in Saudi adults: results from a Saudi national study. Preventive medicine, 36(1), 64-70.
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  The aim of the study was to determine whether there was a relationship between tea consumption and the prevalence of coronary heart disease (CHD) in Saudi Arabia.
• Hakim, I. A., Alsaif, M. A., Aloud, A., Alduwaihy, M., Al-Rubeaan, K., Al-Nuaim, A., & Al-Attas, O. (2003). BlackTea Consumption and serum lipid profiles in Saudi women: A Cross-sectional study in Saudi Arabia. Nutrition Research, 23(11), 1515-1526.
• Hakim, I. A., Harris, R. B., Brown, S., Chow, H. S., Wiseman, S., Agarwal, S., & Talbot, W. (2003). Effect of increased tea consumption on oxidative DNA damage among smokers: a randomized controlled study. The Journal of nutrition, 133(10), 3303S-3309S.
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  Tea drinking has been associated with decreased occurrence of cancer and heart disease. One potential mechanism for these findings is the strong antioxidant effect of tea polyphenols. A phase II randomized controlled tea intervention trial was designed to study the effect of high consumption (4 cups/d) of decaffeinated green or black tea on oxidative DNA damage as measured by urinary 8-hydroxydeoxyguanosine (8-OHdG) among smokers over a 4-mo period. A total of 143 heavy smokers, aged 18-79 y, were randomized to drink either green or black tea or water. Levels of plasma and urinary catechins and urinary 8-OHdG were measured monthly. A total of 133 of 143 smokers completed the 4-mo intervention. Multiple linear regression models were used to estimate the main effects and interaction effect of green and black tea consumption on creatinine-adjusted urinary 8-OHdG, with or without adjustment for potential confounders. Plasma and urinary levels of catechins rose significantly in the green tea group compared with the other two groups. Assessment of urinary 8-OHdG after adjustment for baseline measurements and other potential confounders revealed a highly significant decrease in urinary 8-OHdG (-31%) after 4 mo of drinking decaffeinated green tea (P = 0.002). No change in urinary 8-OHdG was seen among smokers assigned to the black tea group. These data suggest that regular green tea drinking might protect smokers from oxidative damages and could reduce cancer risk or other diseases caused by free radicals associated with smoking.
• Alsaif, M. A., Hakim, I. A., Harris, R. B., Alduwaihy, M., Al-Rubeaan, K., Al-Nuaim, A., & Al-Attas, O. (2002). Prevalence and risk factors of obesity and overweight in adult Saudi population. NUTRITION RESEARCH, 22(11), 1243-1252.
• Chow, H. S., Salazar, D., & Hakim, I. A. (2002). Pharmacokinetics of perillic acid in humans after a single dose administration of a citrus preparation rich in d-limonene content. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 11(11), 1472-6.
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  d-Limonene, a monoterpene, is widely distributed as a natural nonnutritive constituent of a variety of foods and volatile oils, particularly citrus oils. d-Limonene and its derived metabolites have been shown to possess cancer chemotherapeutic and chemopreventive efficacy in various preclinical model systems. In our previous work, we have found that lemonade prepared with the whole lemon (Mediterranean-style lemonade) contains high levels of d-limonene. The current study is designed to determine the systemic availability of perillic acid, a major and biologically active metabolite of d-limonene, after a single dose administration of Mediterranean-style lemonade. Healthy individuals were recruited to consume 30-40 oz of Mediterranean-style lemonade with a light breakfast. Blood samples were collected for up to 24 h after the completion of lemonade consumption. d-Limonene levels in the juice and perillic acid levels in plasma were determined by reversed-phase high-performance liquid chromatography with UV detection. It was found that 40 oz of lemonade contained 596 mg of d-limonene and 30 oz contained 447 mg of d-limonene. Plasma concentrations of perillic acid reached maximal levels at 1 h after the lemonade consumption and declined rapidly as a function of time with the terminal elimination half-life ranging from 0.82 to 1.84 h. The maximum plasma perillic acid concentration ranged from 2.08 to 13.98 micro M, and the levels were undetectable at 24 h after the lemonade consumption. The area under the plasma concentration-time curves of perillic acid ranged from 5.07 to 32.59 (micro M) x h. Our study illustrates that the major metabolite of d-limonene is bioavailable after oral consumption of a citrus preparation rich in d-limonene content.
• Hakim, I. A., Hartz, V., Graver, E., Whitacre, R., & Alberts, D. (2002). Development of a questionnaire and a database for assessing dietary d-limonene intake. Public health nutrition, 5(6A), 939-45.
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  Increasing recognition of the potential importance of phytochemicals in the aetiology of cancer and heart diseases has highlighted the need for methods to measure individual phytochemical consumption that are sufficiently simple to be used in large epidemiological studies and whose reproducibility and accuracy have been quantified. d-Limonene is a natural component of a variety of foods and beverages and is found mainly in citrus fruits. However, d-limonene is not assessed by any nationally available analysis database.
• Dorr, R. T., Chow, H. H., Yang, C. S., Shahi, F., Hara, Y., Hakim, I. A., Dorr, R. T., Crowell, J. A., Chow, H. H., Cai, Y., & Alberts, D. S. (2001). Phase I pharmacokinetic study of tea polyphenols following single-dose administration of epigallocatechin gallate and polyphenon E.. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 10(1), 53-8.
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  Green tea has been shown to exhibit cancer-preventive activities in preclinical studies. Its principal active components include epigallocatechin gallate (EGCG), epigallocatechin (EGC), epicatechin (EC), and epicatechin gallate, of which EGCG is the most abundant and possesses the most potent antioxidative activity. We performed a Phase I pharmacokinetic study to determine the systemic availability of green tea catechins after single oral dose administration of EGCG and Polyphenon E (decaffeinated green tea catechin mixture). Twenty healthy subjects (five subjects/dose level) were randomly assigned to one of the dose levels (200, 400, 600, and 800 mg based on EGCG content). All subjects were randomly crossed-over to receive the two catechin formulations at the same dose level. Blood and urine samples were collected for up to 24 h after oral administration of the study medication. Tea catechin concentrations in plasma and urine samples were determined using high-performance liquid chromatography with the coulometric electrode array detection system. After EGCG versus Polyphenon E administration, the mean area under the plasma concentration-time curves (AUC) of unchanged EGCG were 22.5 versus 21.9, 35.4 versus 52.2, 101.9 versus 79.7, and 167.1 versus 161.4 min x microg/ml at the 200-, 400-, 600-, and 800-mg dose levels, respectively. EGC and EC were not detected in plasma after EGCG administration and were present at low/undetectable levels after Polyphenon E administration. High concentrations of EGC and EC glucuronide/sulfate conjugates were found in plasma and urine samples after Polyphenon E administration. There were no significant differences in the pharmacokinetic characteristics of EGCG between the two study medications. The AUC and maximum plasma concentration (Cmax) of EGCG after the 800-mg dose of EGCG were found to be significantly higher than those after the 200- and 400-mg dose. The AUC and Cmax of EGCG after the 800-mg dose of Polyphenon E were significantly higher than those after the three lower doses. We conclude that the two catechin formulations resulted in similar plasma EGCG levels. EGC and EC were present in the body after the Polyphenon E administration; however, they were present predominantly in conjugated forms. The systemic availability of EGCG increased at higher doses, possibly due to saturable presystemic elimination of orally administered green tea polyphenols.
• Hakim, I. A., & Harris, R. B. (2001). Joint Effects of Citrus Peel Use and Black Tea Intake on the Risk of Squamous Cell Carcinoma of the Skin. BMC Dermatology, 1(3).
• Hakim, I. A., Hartz, V., Harris, R. B., Balentine, D., Weisgerber, U. M., Graver, E., Whitacre, R., & Alberts, D. (2001). Reproducibility and relative validity of a questionnaire to assess intake of black tea polyphenols in epidemiological studies. CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 10(6), 667-678.
• Hakim, I. A., Harris, R. B., & Ritenbaugh, C. (2000). Citrus peel use is associated with reduced risk of squamous cell carcinoma of the skin. NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL, 37(2), 161-168.
• Hakim, I. A., Harris, R. B., & Ritenbaugh, C. (2000). Fat intake and risk of squamous cell carcinoma of the skin. NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL, 36(2), 155-162.
• Hakim, I. A., Harris, R. B., & Weisgerber, U. M. (2000). Tea intake and squamous cell carcinoma of the skin: influence of type of tea beverages. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 9(7), 727-31.
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  Differences in tea drinking habits are likely to vary by populations and could contribute to the inconsistencies found between studies comparing tea consumption and cancer risk. A population-based case-control study was used to evaluate how usual tea consumption patterns of an older population (n = 450) varied with history of squamous cell carcinoma (SCC) of the skin. A detailed tea questionnaire was developed to assess specific tea preparation methods and patterns of drinking. In this southwestern United States population, black tea was the predominant variety of tea consumed. We found no association between the broad definition of any tea consumption and skin SCC. However, the adjusted odds ratios (ORs) for hot and iced black tea intake were 0.63 [95% confidence interval (CI), 0.36-1.10] and 1.02 (95% CI, 0.64-1.63), respectively. Controls were more likely to report usually drinking strong hot tea (OR, 0.74; 95% CI, 0.53-1.03) with increased brewing time (P for trend = 0.03). Adjusting for brewing time, the association between skin SCC and hot black tea consumption suggests a significantly lower risk in consumers of hot tea compared to nonconsumers (OR, 0.33; 95% CI, 0.12-0.87). This is one of the first studies to explore the relation between different types of tea consumption and occurrence of human cancers. Our results show that tea concentration (strength), brewing time, and beverage temperature have major influences on the potential protective effects of hot black tea in relation to skin SCC. Further studies with increased sample sizes are needed to evaluate the interrelationships between preparation techniques, tea type, and other life-style factors.
• Harris, R. B., Weisgerber, U. M., Van-mierlo, C. A., Paetau-robinson, I., Harris, R. B., Hakim, I. A., & Balentine, D. (2000). Preparation, composition and consumption patterns of tea-based beverages in Arizona. Nutrition Research, 20(12), 1715-1724. doi:10.1016/s0271-5317(00)00275-x
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  Abstract Flavonoids in black and green tea have been implicated in cancer chemoprevention. The concentration of flavonoids in tea is likely to vary by preparation techniques. Inconsistencies between epidemiological studies may arise from the lack of information on methods of preparation. The purpose of this study was to assess the pattern of tea consumption among an older Arizonan population and to determine tea polyphenol and flavonoid levels in the most commonly used tea preparation techniques for a Southwestern US population. A specific tea questionnaire was developed using focus groups and semi-structured interviews. The reliability of the tea questionnaire was very high even after 6 months (r= 0.93 for average tea intake/day). Forty samples, representing the most typical preparation techniques of hot, iced, and sun tea, were analyzed by HPLC for total flavonoids, catechins, theaflavins, thearubigins, caffeine and gallic acid. In black tea, the highest concentrations of flavonoids (μg/ml) were found in brewed hot tea (range: 541–692) while the lowest concentrations were for instant tea preparations (range: 90–100). Results show that tea concentration, brewing time, and beverage temperature also have major influences on flavonoid concentrations. Use of specific questions focusing on tea preparation and availability of quantitative estimates of tea flavonoids should enhance epidemiological studies of the relationship between tea consumption and disease risk.
• Hakim, I. (1998). Mediterranean diets and cancer prevention. Archives of internal medicine, 158(11), 1169-70.
• Mohamed, N. H., Hakim, I. A., El-husseiny, S., & Awad, A. H. (1997). Blood Cholesterol and Triglycerides in Adolescent Egyptian Girls: Relation to Anthropometric Measurements. Food and Nutrition Bulletin, 18(1), 56-63. doi:10.1177/156482659701800103
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  High serum cholesterol is a major risk factor for atherosclerosis. This cross-sectional study (n = 102) investigated the levels of total cholesterol (TC) and triglycerides (TG) in Egyptian girls aged 11 to 16 years attending a middle-class public school. The mean TC level was 194.27 ± 21.97 mg/dl, and 33.33% of girls had TC levels > 200 mg/dl. The mean TG level was 160.07 ± 30.83 mg/dl, with 3.92% of the girls showing TG levels > 2 00 mg/dl. Most of the girls (65.69%) were overweight, with body mass index (BMI) >25. Univariate analyses revealed an association of TC and TG with all anthropometric measures. Using stepwise regression analyses, the best model for prediction of TC was with BMI and central body fat (explaining 24.76% of TC variance); the final model for TG was with BMI, central body fat, and abdominal skinfold thickness (explaining 47.49% of TG variance). Our data show that these adolescent Egyptian girls were heavier and had higher blood lipid concentrations than subjects in the Bogalusa study and other studies worldwide. Further studies are needed to determine the factors associated with these higher lipid levels and to develop appropriate intervention programmes.

Proceedings Publications

• Hakim, I. A. (2019). The Impact of the Fourth Industrial Revolution on the Transformation of Global Public Health Education. In 8th Annual Global Health Care Conference.

Poster Presentations

• Morrill, K., Aceves, B., Valdez, L., Thomson, C. A., Hakim, I. A., Bell, M. L., Rabe, B. A., & Garcia, D. O. (2018, Spring). Abstract: . Feasibility and acceptability of a beverage intervention for obese Hispanic adults. SBM. New Orleans, LA.