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Antioxidant supplements may benefit couples who have difficulty conceiving naturally, according to a new systematic review published January 18 in The Cochrane Library. The review provides evidence from a small number of trials that suggest the partners of men who take antioxidants are more likely to become pregnant.

Male subfertility affects one in 20 men. Chemicals called reactive oxygen species (ROS) are said to cause damage to cells, and in particular sperm cells, which may result in lowered sperm counts and interfere with their ability to fertilise eggs. Antioxidants include natural and synthetic chemicals, including certain vitamins and minerals, which help to reduce the damage caused by ROS.

The review focused on 34 trials involving 2,876 couples undergoing assisted reproductive techniques such as in vitro fertilisation and sperm injections. Most men in the trials had low sperm counts or low sperm motility. The trials explored the use of many different types of oral antioxidants, including vitamin E, L-carnitine, zinc and magnesium.

Compared to controls, a couple was more likely to have a pregnancy or live birth if the man took antioxidants. However, these results are based on just 964 of the couples in the review for pregnancies and 214 couples for live births. Other trials tested the effects of antioxidants on sperm motility and concentration and showed mostly positive effects, although study group sizes were small.

"When trying to conceive as part of an assisted reproductive program, it may be advisable to encourage men to take oral antioxidant supplements to improve their partners' chances of becoming pregnant," said lead researcher Marian Showell, who works in Obstetrics and Gynaecology at the University of Auckland in Auckland, New Zealand. "However, these conclusions are currently based on limited evidence."

There were not enough data comparing different antioxidants to reach any conclusions about the relative effectiveness of supplements. "We need more head-to-comparisons to understand whether any one antioxidant is performing better than any other," said Showell.

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According to research conducted at the Oregon National Primate Research Center at Oregon Health & Science University, the commonly held belief that oral contraceptives cause weight gain appears to be false. The results of the study are published online and will appear in next month's edition of the journal Human Reproduction.

"A simple Google search will reveal that contraceptives and the possibility that they may cause weight gain is a very highly debated topic," said Alison Edelman, M.D., a physician and researcher in the Department of Obstetrics and Gynecology at OHSU and lead author of the study.

"Issues surrounding weight are hard to study in humans, and the research thus far has been insufficient to demonstrate whether or not oral contraceptives cause weight gain or loss. But this is an extremely important question as concern about weight gain is one of the main reasons why women may avoid or discontinue birth control, which in turn places them at greater risk for an unplanned pregnancy."

To conduct their research, scientists and physicians studied a group of rhesus macaque monkeys at the OHSU Oregon National Primate Research Center for almost a year. Rhesus monkeys were used in this study because their reproductive system is nearly identical to humans. However, unlike human studies, more variables can be controlled and measured -- such as exact food intake -- to provide more meaningful data.

At the beginning of the study, half the animals were obese and half were normal weight. During the eight-month treatment period, animals received doses of oral contraceptives, adjusted to the weight of the animals so that it mimicked dosage in humans. Researchers tracked weight, food intake, activity levels, body fat and lean muscle mass. At the study's conclusion, the normal weight group remained weight stable whereas the obese group lost a significant amount of weight (8.5%) and percent of body fat (12%) due to an increase in basal metabolic rate. No changes were seen in food intake, activity or lean muscle mass for either group.

"This study suggests that worries about weight gain with pill use appear to be based more on fiction than on fact," said Judy Cameron, Ph.D., senior author of the paper and a researcher at the primate center.

"Additionally, there may be a differential affect depending on your starting weight -- heavier individuals who keep their diet stable may see a weight loss with pill use. Most likely, the reason why this belief continues to exist is that the weight gain that seems to occur with age is being attributed to these medications. We realize that research in nonhuman primates cannot entirely dismiss the connection between contraceptives and weight gain in humans, but it strongly suggests that women should not be as worried as they previously were.

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It is becoming well accepted that, as well as too little exercise, too much sitting is bad for people's health. Now a new study has found that it is not just the length of time people spend sitting down that can make a difference, but also the number of breaks that they take while sitting at their desk or on their sofa. Plenty of breaks, even if they are as little as one minute, seem to be good for people's hearts and their waistlines.

The study, which is published online on January 12 in the European Heart Journal, is the first in a large, representative, multi-ethnic population to look at the links of the total amount of time spent sitting down and breaks in sedentary time, with various indicators of risk for heart disease, metabolic diseases such as diabetes, and inflammatory processes that can play a role in atherosclerosis (blocked arteries).

It found that prolonged periods of sedentary time, even in people who also spent some time in moderate-to-vigorous exercise, were associated with worse indicators of cardio-metabolic function and inflammation, such as larger waist circumferences, lower levels of HDL ("good") cholesterol, higher levels of C-reactive protein (an important marker of inflammation) and triglycerides (blood fats).

However, the study also found that, even in people who spent a long time sitting down, the more breaks they took during this time, the smaller their waists and the lower the levels of C-reactive protein.

There were some racial and ethnic differences. The most significant was that longer sedentary time had a marked adverse effect on waist circumference for non-Hispanic whites only, but made no difference to Mexican Americans and appeared to be beneficial for non-Hispanic blacks.

Dr Genevieve Healy, a research fellow at the School of Population Health, The University of Queensland, Australia, who led the study, said: "Overall, for length of sedentary time, the most clinically significant findings were for blood fats and markers of insulin resistance. For the number of breaks in sedentary time, the most significant differences were observed for waist circumference. The top 25% of people who took the most breaks had, on average, a 4.1cm smaller waist circumference than those in the lowest 25%."

Dr Healy and her colleagues analysed data from 4,757 people aged 20 and over, who took part in the US National Health and Nutrition Examination Survey between 2003 and 2006. The participants wore a small device called an accelerometer, which monitored the amount and intensity of walking or running activity. It was worn on the right hip during waking hours for seven days and it gave researchers information on sedentary time and breaks in sedentary time. Measurements were taken of waist circumference, blood pressure, cholesterol levels and C-reactive protein concentrations, and they also measured levels of triglycerides, plasma glucose and insulin in a sub-sample of participants who were fasting when attending a morning examination. The researchers accounted statistically for socio-demographic differences between study participants, their medical histories and their lifestyles (smoking, alcohol intake, diet).

The least amount of sedentary time was 1.8 hours per day, the most 21.2 hours per day; the least number of breaks over the full seven days was 99, and the most was 1,258.

Dr Healy said: "The benefits of regular participation in moderate-to-vigorous intensity exercise are well accepted scientifically and by the general public. However, the potential adverse health impact of prolonged sitting (which is something that we do on average for more than half of our day), is only just being realised. Our research highlights the importance of considering prolonged sedentary time as a distinct health risk behaviour that warrants explicit advice in future public health guidelines. In particular, the findings are likely to have implications for settings where prolonged sitting is widespread, such as in offices.

"Our research showed that even small changes, which could be as little as standing up for one minute, might help to lower this health risk. It is likely that regular breaks in prolonged sitting time could be readily incorporated into the working environment without any detrimental impact on productivity, although this still needs to be determined by further research. 'Stand up, move more, more often' could be used as a slogan to get this message across."

She said that existing occupational health and safety guidelines recommend regular changes in posture and a variety of work tasks, and that these would help to incorporate more breaks from sitting in the working day, and might lead to less sedentary time overall. Practical tips that might help to do this in an office-based workplace included:

* Standing up to take phone calls
* Walking to see a colleague rather than phoning or emailing
* Having standing meetings or encouraging regular breaks during meetings for people to stand up
* Going to a bathroom on a different level
* Centralising things such as rubbish bins and printers so that you need to walk to them
* Taking the stairs instead of the lift where possible.

Dr Healy said that the size of the differences in the various cardio-metabolic and inflammatory risk biomarkers between the top and bottom 25% of people in terms of their sedentary time was large enough to suggest that "in theory, population-wide reductions in sedentary time of between one to two hours a day could have a substantial impact on the prevention of cardiovascular disease."

She concluded: "Prolonged sedentary time is likely to increase with future technological and social innovations, and it is important to avoid prolonged periods of sitting and to move more throughout the day. Reducing and regularly breaking up sedentary time may be an important adjunct health message, alongside the well-established recommendation for regular participation in exercise. While further evidence of a causal nature is required, less sitting time would be unlikely to do harm. It would, at the very least, contribute to increased overall levels of daily energy expenditure and could help to prevent weight gain."

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For postmenopausal women with osteopenia (low bone mineral density), practicing tai chi and/or taking green tea polyphenols appears to be safe. Further, practicing tai chi by itself or in combination with green tea polyphenol supplements may improve quality of life; however, taking green tea supplements by themselves has no significant improvement in quality of life. This is according to a recent NCCAM-funded study published in BMC Complementary and Alternative Medicine. Osteopenia may precede osteoporosis, a bone disease characterized by reduced bone strength that can lead to fractures—a significant cause of disability in older people.

Previous clinical studies have suggested that tai chi—a traditional Chinese practice involving physical movement, mental focus, and deep breathing—has beneficial effects on bone health. Likewise, animal research has indicated that green tea polyphenols (substances rich in antioxidants) also may have bone-protective effects. However, there is limited information on the long-term safety of green tea supplements in people as well as several reports concerning their adverse effects on liver and kidney function. To further build on this evidence and to evaluate the effect of tai chi in combination with green tea polyphenol supplements, NCCAM-funded researchers investigated the safety and impact on quality of life of these interventions in postmenopausal women with osteopenia. (This study is part of a larger research project that is investigating the effects of green tea polyphenols and tai chi on bone health in postmenopausal women with low bone mineral density. Results of other findings from the study—bone, inflammation, and stress parameters—will be published at a later date.)

Researchers from Texas Tech University randomly assigned 171 women to receive green tea polyphenols (500 mg daily); green tea polyphenols plus tai chi training; placebo pills (500 mg starch daily); or placebo pills plus tai chi training over a 24-week period. The tai chi training consisted of three 60-minute sessions per week. Researchers measured participants' depression (mood) and general health status, as well as liver and kidney function throughout the study. Participants in the tai chi groups reported significant beneficial effects in quality of life in terms of improving their emotional and mental health. The researchers found that green tea supplements did not significantly affect participants' liver enzymes or kidney serum levels and had no effect on quality of life.

The researchers noted that this is the first placebo-controlled, randomized study to evaluate the safety of long-term use of green tea supplements in postmenopausal women. Based on these findings, the researchers concluded that green tea polyphenols at a dose of 500 mg daily for 24 weeks, alone or in combination with tai chi, appears to be safe in postmenopausal women with low bone mineral density.

Reference

• Shen C-L, Chyu M-C, Pence BC, et al. Green tea polyphenols supplementation and tai chi exercise for postmenopausal osteopenic women: safety and quality of life report. BMC Complementary and Alternative Medicine. 2010;10(1):76. [Epub ahead of print]

Additional Resources

• Tai Chi


• Green Tea



• Bone Mass Measurement: What the Numbers Mean (NIAMS)


• Tai Chi May Help Maintain Bone Mineral Density in Postmenopausal Women

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Antioxidants are sold over the counter everywhere. They’re added to food, drink, and face cream. But according to Prof. Nava Dekel of the Weizmann Institute of Science’s Department of Biological Regulation, we still don’t have a complete understanding of how they act in our bodies. New research by Prof. Dekel and her team, recently published in the Proceedings of the National Academy of Sciences (PNAS), has revealed an unexpected possible side effect of antioxidants: they might cause fertility problems in females.

Common antioxidants include vitamins C and E. These work by eliminating molecules called reactive oxygen species that are produced naturally in the body. Stress can cause these chemically active molecules to be overproduced; in large amounts they damage cells indiscriminately. By neutralizing these potentially harmful substances, antioxidants may, theoretically, improve health and slow down the aging process.

But when Prof. Dekel and her research team, including her former and present PhD students Dr. Ketty Shkolnik and Ari Tadmor, applied antioxidants to the ovaries of female mice, the results were surprising: ovulation levels dropped precipitously. That is, very few eggs were released from the ovarian follicles to reach the site of fertilization, compared to those in untreated ovaries.

To understand what lies behind these initial findings, the team asked whether it is possible that the process of ovulation might rely on the very “harmful” substances destroyed by antioxidants – reactive oxygen species.

Further testing in mice showed that this is, indeed, the case. In one experiment, for instance, Prof. Dekel and her team treated some ovarian follicles with luteinizing hormone, which is the physiological trigger for ovulation, and others with hydrogen peroxide, which is a reactive oxygen species. The results showed hydrogen peroxide fully mimicked the effect of the ovulation-inducing hormone. This implies that reactive oxygen species that are produced in response to luteinizing hormone serve, in turn, as mediators for this physiological stimulus leading to ovulation.

Among other things, these results help fill in a picture that has begun to emerge in recent years of fertility and conception, in which it appears that these processes share a number of common mechanisms with inflammation. It makes sense, says Prof. Dekel, that substances which prevent inflammation in other parts of the body might also get in the way of normal ovulation, and so more caution should be taken when administering such substances.

Much of Prof. Dekel’s research has focused on fertility – her previous results are already helping some women become pregnant. Ironically, the new study has implications for those seeking the opposite effect. According to Prof. Dekel, “On the one hand, these findings could prove useful to women who are having trouble getting pregnant. On the other, further studies might show that certain antioxidants might be effective means of birth control that could be safer than today’s hormone-based prevention.”

Prof. Dekel and her team are now planning further studies to investigate the exact mechanics of this step in the fertility process: to find out just how, when, and where antioxidants affect the ovaries, and to examine their effect on mice when administered in either food or drink. In addition, they plan to collect data on the possible link between females taking antioxidant supplements and difficulty conceiving.

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NSAID Receptor Responsible for Olive Oil’s ‘Cough’ and More


Combination of sensory and molecular approaches identify receptor sensitive to anti-inflammatory compounds


Scientists from the Monell Center and collaborators report that a receptor known as TRPA1 is activated by two structurally unrelated anti-inflammatory compounds. The first, oleocanthal, is a natural polyphenolic anti-inflammatory agent uniquely found in extra virgin olive oil; while the second, ibuprofen, is an over-the-counter non-steroidal anti-inflammatory drug (NSAID).

The researchers also demonstrate that the TRPA1 receptor is spatially localized to the back of the throat, which is exactly where the distinctive irritating sting from olive oil is felt. This unique sensation and the accompanying ‘cough’ are regarded among connoisseurs as indicators of high quality olive oil.

“We believe that the TRPA1 receptor elicits cough to protect the lungs from chemical insult, for example from toxins in the air,” said Paul A.S. Breslin, Ph.D., one of the corresponding authors and a sensory biologist at Monell.

In 2005, Monell researchers and collaborators announced the discovery that oleocanthal is a non-steroidal, anti-inflammatory agent that inhibits activity of cyclooxygenase (COX) enzymes, a pharmacological action shared by ibuprofen.

The finding was based on the sensory observation that olive oil irritates the back of the throat in a highly characteristic manner identical to that experienced with liquid ibuprofen.

At that time, the researchers also demonstrated that oleocanthal caused the irritating throat sting associated with extra virgin olive oils.

The current study, published in the Journal of Neuroscience, extends those findings by identifying TRPA1 as the receptor that is activated by both oleocanthal and ibuprofen. Further, the findings establish that oleocanthal causes the distinctive sting of olive oil through its activation of TRPA1. Similarly, activation of the same receptor produces ibuprofen’s irritating sensation.

The findings may provide novel insights into anti-inflammatory pharmacology. “This receptor may be used to identify other anti-inflammatory compounds that, like ibuprofen and oleocanthal, help prevent major lethal disease,” said Breslin.

“Additionally, since we know how to inhibit this receptor, it may be possible to develop liquid anti-inflammatory medicines that are less aversive. This would especially benefit children, who are unable to swallow pills.”

The study’s combination of sensory, chemical, and molecular approaches may lend insight into other aspects of inflammation and disease.

“Oleocanthal and ibuprofen are chemically unrelated, yet both are potent anti-inflammatory compounds that activate the TRPA1 receptor and cause sensory irritation,” said Monell behavioral biologist Gary K. Beauchamp, Ph.D., also a corresponding author. “This points to a possible mechanistic connection between sensory perception, receptor activation, and pharmacology. An understanding of this connection could someday lead to identification of new anti-inflammatory pathways.”

Future work also will explore several paradoxical associations that relate the sensory and health-promoting aspects of oleocanthal and ibuprofen. Lead author Catherine Peyrot des Gachons, Ph.D., a food scientist at Monell, points out that the two anti-inflammatories promote health while also causing irritation and pain. She comments, “These two facts seem antagonistic and excitingly mysterious from a scientific perspective.”

Beauchamp raises a related question, noting that humans have come to appreciate the ‘pain’ from oleocanthal in olive oil, as if there is an inner knowledge that it is advantageous. “How this happens remains a fascinating puzzle,” he says.

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Does eating a big breakfast help weight loss or is it better to skip breakfast altogether? Available information is confusing but new research published in BioMed Central's open access journal Nutrition Journal clears a path through these apparently contradictory reports.

Dr Volker Schusdziarra, from the Else-Kröner-Fresenius Center of Nutritional Medicine, conducted a study on over 300 people who were asked to keep a journal of what they usually ate. Within the group sometimes people ate a big breakfast, sometimes small, and sometimes skipped it all together.

Schusdziarra said that "the results of the study showed that people ate the same at lunch and dinner, regardless of what they had for breakfast", this means that a big breakfast (on average 400kcal greater than a small breakfast) resulted in a total increase in calories eaten over the day of about 400kcal. The only difference seen was the skipping of a mid morning snack when someone ate a really big breakfast, however this was not enough to offset the extra calories they had already eaten.

The group addressed previous research, which suggests that eating a big breakfast reduces total calorie intake over the day, and showed that this data is misleading. This earlier research only looked at the ratio of breakfast calories to daily calories and in Schusdziarra's study this ratio seems to be most affected by people eating less during the day. In other words their breakfast was proportionally, but not absolutely, bigger. So it seems that there is no magic and that, unfortunately, in the fight for weight-loss, eating a large breakfast must be counteracted by eating substantially less during the rest of the day. In order to lose weight sensibly NHS guidelines suggest restricting calorie intake, cutting down on saturated fat and sugar, and eating 5-a-day fruit and veg.