Antioxidants May Enhance Efficacy of Chemotherapy on Glioblastoma

MedicalResearch.com Interview with:

Dr. Scott Litofsky, MD  Division of Neurological Surgery University of Missouri-Columbia School of Medicine Columbia, MO 65212 

Dr. Litofsky

Dr. Scott Litofsky, MD
Division of Neurological Surgery
University of Missouri-Columbia School of Medicine
Columbia, MO 65212 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Many patients take over-the-counter medications to held their cancers. Some of these remedies may be helpful; others are potentially harmful. Anti-oxidant medications are frequently selected by patients as they are inexpensive and available.

We were approached by a high school student, Macy Williams (one of the authors) to do some research in our laboratory when she won a research scholarship (the 2016 Emperor Science Award) from Stand Up to Cancer. She worked with us several times per week doing experiments during her senior year of high school. When she graduated, we continued the work that she started.

We studied effects of Vitamin D3, Melatonin, and alpha-Lipoic Acid on glioblastoma cells, a highly malignant brain tumor. We included experiments of these agents alone and in combination with Temozolomide, a chemotherapy agent used as standard of care in glioblastoma. The work was done in cultured cells, measuring growth and survival of cells. We used concentrations that could be achieved by oral intake of the drugs.

We found that antioxidant medications, particularly alpha Lipoic Acid, had synergistic effects with Temozolomide – that is Temozolomide impair glioblastoma cell growth and survival better when combined with an antioxidant. The mechanism of action may be through reactive oxygen species.  Continue reading

Cystic Fibrosis: Antioxidant-Enriched MVI May Decrease Respiratory Illnesses

MedicalResearch.com Interview with:

Scott D Sagel MD PhD Professor of Pediatrics University of Colorado School of Medicine Aurora, Colorado

Dr. Sagel

Scott D Sagel MD PhD
Professor of Pediatrics
University of Colorado School of Medicine
Aurora, Colorado

MedicalResearch.com: What is the background for this study?

Response: Inflammation is an important feature of cystic fibrosis (CF) lung disease and contributes to lung damage and lung function decline in CF. We need safe and effective anti-inflammatory treatments in CF. Anti-oxidant therapy has been an area of promise, but with mixed results in CF.

This clinical trial, conducted at 15 CF centers affiliated with the cystic fibrosis Foundation Therapeutics Development Network, enrolled 73 patients who were 10 years and older (average age 22 years), with pancreatic insufficiency, which causes malabsorption of antioxidants. Subjects were randomized to either a multivitamin containing multiple antioxidants including carotenoids such as beta(β)-carotene, tocopherols (vitamin E), coenzyme Q10 (CoQ10), and selenium or to a control multivitamin without antioxidant enrichment. The antioxidants used in the study were delivered in a capsule specifically designed for individuals with difficulties absorbing fats and proteins, including those with cystic fibrosis.

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Association Between Dietary Intake and Function in Amyotrophic Lateral Sclerosis

MedicalResearch.com Interview with:

Dr. Jeri Nieves PhD Director of bone density testing New York's Helen Hayes Hospital

Dr. Jeri Nieves

Dr. Jeri Nieves PhD
Director of bone density testing
New York’s Helen Hayes Hospital

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Amyotrophic lateral sclerosis (ALS) is a devastating severe neurodegenerative disorder that causes progressive muscle atrophy, paralyses, and eventual respiratory failure.

Our objective was to evaluate the associations between nutrition and severity of ALS around the time of diagnosis. This was a cross-sectional analysis of data from a multicenter cohort of 302 patients with ALS. We assessed nutrient intake using a modified Block Food Frequency Questionnaire. The outcomes were respiratory function (measured using percentage forced vital capacity; FVC%) and functional performance measured by ALS Functional Rating Scale–Revised (ALSFRS-R), both considered important indicators of the severity of ALS. Results of the regression analysis were that higher intakes of antioxidants and carotenes from vegetable intake were associated with higher ALSFRS-R scores or better %FVC.

We used a novel analysis to evaluate the diet as a whole and found that higher intakes of antioxidants, fiber from grains, vegetables, fruit, eggs, fish, and poultry were all associated with higher function in patients with ALS. However, milk and lunch meats were associated with lower measures of function. These consistent results from two different statistical analyses indicate that diet may help minimize the severity of ALS. Perhaps these findings point to the role of oxidative stress in ALS severity.

In summary, increased consumption of antioxidant nutrients, foods high in carotenoids and fiber, vegetables and fruits, poultry and fish are associated with better function around the time of ALS diagnosis.

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Antioxidants May Encourage Lung Cancer and Melanoma to Spread

Prof. Martin O. Bergo Sahlgrenska Cancer Center Department of Molecular and Clinical Medicine Institute of Medicine University of Gothenburg Gothenburg, Sweden

Prof. Martin O. Bergo

MedicalResearch.com Interview with:
Prof. Martin O. Bergo
Sahlgrenska Cancer Center
Department of Molecular and Clinical Medicine
Institute of Medicine
University of Gothenburg
Gothenburg, Sweden

Medical Research: What is the background for this study? What are the main findings?

Prof. Bergo: Dietary antioxidants and antioxidant supplements can protect cells and people from harmful effects of free radicals. The free radicals have the potential, over time, to cause cancer. But why is this research field so enormously fraught with controversy, and why have clinical trials with antioxidants not established this potential anti-cancer effects? We believe it is because the question of “whether antioxidants protect against cancer” should be divided into two separate questions:

1. Do antioxidants protect a healthy cell or a tumor-free person from cancer in the future.?and

2. What is the impact of antioxidant supplementation on an already established tumor?

Focusing specifically on the second question, we showed previously that the antioxidants N-acetylcysteine and vitamin E markedly increase lung cancer progression in mice and cause human lung cancer cells to proliferate faster. The mechanism for this effect was directly linked to the ability of the antioxidants to scavenge free-radicals, which is why it is likely that other antioxidants, synthetic or natural, could have a similar effect. In the current study, we argued that it would be important to test this in malignant melanoma for three reasons.

First, melanoma cancer cells are known to be sensitive to changes in free radicals. Second, melanoma is the cancer that increases most in incidence and lethality in the western world.
And third, primary melanomas may be exposed to antioxidants from both the diet and from skin lotions and sun creams.

We found that supplementing the diet of mice with acetylcysteine has no impact on the primary tumors on the skin but doubles the rate of metastasis – i.e. the ability of the tumor cells to spread in the body. We found similar results with human malignant melanoma cells in culture: antioxidants (acetylcysteine and vitamin E) increased their ability to migrate and invade surrounding tissue. Thus, all in all, we have found that antioxidants can worsen cancer in two different ways, one in the lung, and another in the skin.    

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Antioxidants May Have Mixed Effect on Aging

Dr. Jeremy Van Raamsdonk Laboratory of Aging and Neurodegenerative Disease (LAND), Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, Michigan, Department of Translational Science and Molecular Medicine, Department of Genetics, Michigan State University, East Lansing, Michigan, Department of Biology, McGill University, Montreal, Quebec, CanadaMedicalResearch.com Interview with:
Dr. Jeremy Van Raamsdon PhD
Laboratory of Aging and Neurodk egenerative Disease (LAND),
Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, Michigan, Deptment of Translational Science and Molecular Medicine, Department of Genetics, Michigan State University, East Lansing, Michigan,Dep. of Biology, McGill University, Montreal, Quebec, Canada

Medical Research: What is the background for this study? What are the main findings?

Dr. Van Raamsdonk : The free radical theory of aging is one of the most widely accepted theories of aging. This theory suggests that reactive oxygen species (ROS), which are also known as free radicals, cause a type of damage, called oxidative damage, that accumulates over time to cause the functional decline associated with aging. ROS have also been proposed to play a role in many diseases including neurodegenerative disorders such as Parkinson’s disease and Huntington’s disease.

However, recent work has demonstrated that ROS are not necessarily detrimental. ROS perform functional roles in the body and thus it is possible to have too little ROS. We previously showed that increasing ROS by decreasing the levels of an antioxidant enzyme called superoxide dismutase (SOD) does not decrease lifespan even when all of the SOD genes are removed. We also showed that in some cases treatment with an antioxidant, such as Vitamin C, can lead to decreased lifespan. This finding is consistent with human clinical trials in which it has not been possible to show a beneficial effect of antioxidants on longevity.

In this paper we further examine the relationship between ROS and aging. We use a simple genetic model organism, the worm Caenorhabditis elegans, which has been used extensively in aging research, to determine how location impacts the effect of ROS on lifespan. We used a genetic approach to increase the levels of ROS in different parts of a cell and found that location is crucial in determining the effect of ROS on lifespan. Mildly increasing the levels of ROS in the mitochondria increases lifespan, while increasing ROS in the cytoplasm has the opposite effect of decreasing lifespan.

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Healthy Lifestyle, Not Supplements, Linked to Longevity

Annlia Paganini Hill PhD Project Scientist Biostatistician and Epidemiologist Department of Neurology, School of Medicine University of California, Irvine, Irvine, CaliforniaMedicalResearch.com Interview with:
Annlia Paganini Hill PhD
Project Scientist Biostatistician and Epidemiologist
Department of Neurology, School of Medicine
University of California, Irvine, Irvine, California

Medical Research: What is the background for this study? What are the main findings?

Response: Free radicals are formed when one exercises and when the body converts food to energy. Environmental sources (e.g. smoke, air pollution, sunlight) also expose the body to free radicals. Free radicals can cause “oxidative stress” and damage cells. Oxidative stress is thought to play a role in a variety of diseases: cancer, cardiovascular disease, diabetes, Alzheimer’s disease, Parkinson’s disease, cataracts, and age-related macular degeneration.

Antioxidants are man-made or natural substances that may prevent or delay some types of cell damage. Antioxidants are found in many foods and are also available as dietary supplements. Vegetables and fruits are rich sources of antioxidants. There is good scientific evidence that eating a diet with lots of vegetables and fruits is healthful and lowers risks of certain diseases. However, it is unclear whether this is because of the antioxidants, something else in these foods, other foods in people’s diet, or other lifestyle choices.

While antioxidants have been shown to counteract oxidative stress in cells and animal studies, whether consuming large amounts of antioxidant supplements benefits human health is debated. Given the continued use of vitamin supplements by a large proportion of the population and the presumed safety of antioxidant supplementation, we assessed the relationship between antioxidant vitamin intake and all-cause mortality in older adults.

We examined these associations using data from the Leisure World Cohort Study, a study of nearly 14,000 residents of a California retirement community. In the early 1980s, participants (median age, 74 years) reported details on use of vitamin supplements and dietary intake of foods containing vitamins A and C. During followup (1981-2013), over 93% of participants had died (median age at death, 88 years).

Medical Research: What are the main findings?

Response: Previously, we had found that a number of factors were associated with lower risk of death in our cohort — not smoking, physical activity, moderate alcohol consumption, caffeine intake, ideal body mass index (neither too fat nor too thin), and no history of high blood pressure, angina, heart attack, stroke, diabetes, rheumatoid arthritis, or cancer .

Neither dietary nor supplemental intake of vitamins A, C or E were significantly associated with reduced mortality in this study once these other lifestyle behaviors and disease conditions were taken into account.

In Leisure World Cohort and in the general population, health-promoting habits often cluster; e.g. those who take vitamin supplements often exercise, do not smoke, and are not obese. Thus, these factors explain the observed association between longevity and vitamin supplements in our and previous studies.

Medical Research: What should clinicians and patients take away from your report?

Response: Antioxidant supplements should not be used to replace a nutritionally adequate diet. A healthful diet characterized by high amounts of fruits and vegetables, whole grains, and fish should be recommended to avoid nutritional deficiencies and to prevent chronic disease.

Additionally, other studies have shown that high-dose antioxidant supplements may even be harmful (increased risks of prostate cancer, hemorrhagic stroke, and lung cancer in smokers). And because antioxidant supplement may interact with other medications, use of supplements should be discussed with a health care provider.

Citation:

Antioxidant Vitamin Intake and Mortality: The Leisure World Cohort Study.

Paganini-Hill A, Kawas CH, Corrada MM.
Am J Epidemiol. 2014 Dec 29. pii: kwu294. [Epub ahead of print]

 

 

 

Macular Degeneration: Incidence, Susceptibility and Dietary Antioxidants

Jie Jin Wang MMed (Clin Epi) MAppStat PhD Professor Australian NHMRC Senior Research Fellow (Level B) Centre for Vision Research Westmead Millennium Institute University of Sydney C24 Westmead Hospital, NSW 2145 AustraliaMedicalResearch.com Interview with:
Jie Jin Wang MMed (Clin Epi) MAppStat PhD
Professor Australian NHMRC Senior Research Fellow (Level B)
Centre for Vision Research
Westmead Millennium Institute University of Sydney C24
Westmead Hospital, NSW 2145 Australia

MedicalResearch.com: What are the main findings of the study?

Answer: We documented a consistent association between high dietary intake of lutein/zeaxanthin (LZ) and a reduced long-term risk of early age-related macular degeneration (AMD) in persons who carry ≥2 risk alleles of either or both the complement factor H (CFH-rs1061170) and/or the age-related maculopathy susceptibility gene 2 (ARMS2-rs10490924) in two older population-based cohorts.
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Hearing Loss and Dietary Antioxidants

http://ajcn.nutrition.org/content/early/2013/11/06/ajcn.113.068437.abstractMedicalResearch.com Interview with:
Sung Kyun Park, Sc.D., M.P.H

Assistant Professor, Epidemiology
Assistant Professor, Environmental Health Sciences
Departments of Epidemiology and Environmental Health Sciences
University of Michigan School of Public Health
Ann Arbor, MI

MedicalResearch.com: What are the main findings of the study?


Answer: This study reports that persons who eat more dietary antioxidants (beta carotene and vitamin C) or magnesium have a lower risk of hearing loss. This finding was seen in the levels currently observed in the general US population and independent of demographic and socioeconomic factors, noise exposures from workplaces, recreations or firearms, and other potential risk factors.
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Diabetes: Are Antioxidants Really a Good Idea?

Kumar Sharma, M.D. Professor of Medicine Director, Institute of Metabolomic Medicine Director, Center for Renal Translational Medicine University of California, San Diego La Jolla, CA 92093-0711MedicalResearch.com Interview with:
Kumar Sharma, M.D.
Professor of Medicine
Director, Institute of Metabolomic Medicine
Director, Center for Renal Translational Medicine
University of California, San Diego
La Jolla, CA 92093-0711

MedicalResearch.com: What are the main findings of the study?

Dr. Sharma: Main findings are that diabetes is associated with reduced superoxide production in the kidney and heart and that stimulation of superoxide production with AMPK led to improvement in organ function.
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