When you take an antibiotic it causes a disturbance in the friendly neighborhood of the gastrointestinal tract. The normally residential mixture of flora (bacteria) keeps your bowel working appropriately in the course of digestion and is necessary for vitamin production and nutrient absorption. If any portion of the gut’s natural environment is destroyed, the wrong bacteria may overgrow or the right ones become depleted. (As soon as I start to discuss environmental mayhem, many of you probably think I’m “going” global warming, green party or just plain Democrat on you…while the latter may represent my leanings, it doesn’t apply to this article…)

An article titled “Probiotics for the Prevention and Treatment of Antibiotic-Associated Diarrhea” in the May 9 issue of JAMA caught my attention. After all, I like all physicians, have to prescribe antibiotics when necessary. There is approximately a 30% chance of developing diarrhea with use of antibiotics, which is then termed antibiotic-associated diarrhea (AAD)…duh. The symptoms are usually mild but if there is an overgrowth of bacteria such as Clostridium difficile it can be severe. (See my March article on the subject titled “Treating that Awful Reflux: Possible Risk of Severe Intestinal Infection”). Developing diarrhea while on an antibiotic is the most common reason for stopping the antibiotic before completing a full course. This non adherence can result in complications: the infection is not cured or resistant bacteria emerge. Probiotics consist of good or normal gut bacteria and often contain active strains of Lactobacillus, Bifidobacterium, Saccharomyces, Streptococcus, Enterococcus and/or Bacillus. (I’m including their names for any microbiologists that are reading this or for those of you who read the labels, and no, the article in JAMA does not mention ingestion of yogurt.)

After searching on twelve electronic databases, the authors eliminated (yes this is a pun) over 2,348 publications and analyzed 82 studies in which scientifically randomized and controlled groups of patients were given an antibiotic with and without probiotics and the outcome and the incidence of AAD was reported. The overall results were combined and calculated by sophisticated use of statistics (meta-analysis). The final tally showed that with the use of probiotics, when given in conjunction with antibiotics, there was a 58% lower risk (compared to those who did not receive the probiotic) in the development of diarrhea. The authors go on to state however (and if you noticed there is always a “however”) that most of the interventions used poorly documented blends of bacterial types, species, strains and concentration.

There are certainly some antibiotics that are more harmful to the gut environment then others and many of the studies did not specify the antibiotic used. (I will tell you from clinical experience that the more broad spectrum the antibiotic, the more likely that diarrhea will occur…I am especially wary of Ciprofloxacin, Levoquine but any antibiotic can be “gut reprehensible”.) Additional issues brought up by the authors included the need for additional research as to the optimal dose of the probiotic preparation and the comparative effectiveness of the different products.

So as usual, analysis of “what is out there” brings up the need to do more research. But all in all the review did find that there is sufficient evidence that probiotics, when given together with antibiotics reduce the risk of AAD.

All of us will go through menopause and a third of women will have a hysterectomy by the age of 60. Do either or both increase the occurrence of negative mood, (hereafter to be used to connote depressive and anxiety symptoms)? Well what a coincidence that you ask! An article in the May issue of the Journal Obstetrics and Gynecology titled “Mood Symptoms After Natural Menopause and Hysterectomy With and Without Bilateral Oophorectomy among Women in Midlife” deals with this subject. (Yes it’s a long title… and by the way, bilateral oophorectomy means removal of both ovaries.)

The article is based on data from the “Study of Women’s Health Across the Nation” which followed 1,970 women between the ages of 42 and 52 for up to 10 years. During this period, the presence and/or absence of depressive symptoms was assessed by trained interviewers with a 20-item depressive symptom scale on a yearly basis. The women’s anxiety was assessed with 4 questions (and no, they had nothing to do with those of the Passover Hagadah) asking about the number of days in the two weeks prior to their visit that the woman had “irritability or grouchiness”, were “feeling tense or nervous”, felt  “heart pounding or racing” or “felt fearful with no reason”. The researchers then assessed whether the women had had a hysterectomy and if so, with or without an oophorectomy. Now, if you want to know the exact numbers while anticipating the results (hopefully, with no great nervousness or pounding heart), here they are:

A total of 1,793 women reached natural menopause, 76 had had a hysterectomy with ovarian conservation and 101 women had a hysterectomy and bilateral oophorectomy.  The participants were followed for up to 10 years after baseline. (There was an interesting disclaimer that was put in the study whilst describing results…for an unknown reason the women at the New Jersey site, all 131, were not included in the final results due to “reasons unrelated to scientific integrity”. As a former New Jersey-ite I had to wonder why?)

The researchers found that depressive symptoms declined before the final menstrual period or surgery and continued to decline after both. Moreover, regardless of whether the ovaries were conserved or removed, hysterectomy status has no effect on depressive symptoms initially or later. And anxiety scores did not change significantly in the years leading up to the final menstrual period or surgery, but they decreased during the period after the onset of menopause or surgery. Once more, regardless of whether the ovaries were conserved, hysterectomy had no effect on anxiety symptoms at the first annual visit or in the years that followed.

Now, for the caveats; which in this study are huge.  Firstly, the study was limited to women in mid-life close to the onset on natural menopause. We know that there can be significant health and mental risks subsequent to oophorectomy in younger women who have not already begun to experience the hormonal changes of menopause. In general early surgical menopause has been associated with significant mood changes, bone loss, possibly increased risk of heart disease and early onset of Alzheimer’s.) Secondly, and this is a big one… The authors stated that the “use of hormone therapy was associated with lower levels of anxiety and depressive symptoms. Hormones were used at some point by the majority of participants and, as expected, were particularly common among women with a hysterectomy.” but when they excluded the women who after menopause or hysterectomy with oophorectomy did not use hormone therapy, the trajectory of depressive or anxiety symptoms was not changed. Their final conclusion was that lasting effects on both anxiety and depressive symptoms do not need to be a major consideration for deciding whether to keep the ovaries during a hysterectomy.

I realize this was a somewhat confusing article with lots of facts that are first stated and then discussed with a scientific “there were exceptions and additional factors”. I, too, sometimes wonder why certain studies are published. Does this one mean that we should take hormones to preclude mood symptoms during or subsequent to menopause, after a mid-life hysterectomy or removal of the ovaries or not? As usual the answer has to be geared to the individual woman and requires consultations with her physician. But what I think it does say is that no matter what we do, once we go through the menopause transition, whatever mood changes we experience at that time, won’t get worse in the years to come.

When I take a history from a new patient or update her history during a return visit, I always ask her what medications she is currently taking. After she relates her prescription meds, I then inquire about her use of supplements, over-the-counter substances and alternative therapies. And the list is usually long; hence, I read with great interest a “Viewpoint” article that appeared in the May 2 issue of JAMA. It was titled “Studying Complementary and Alternative Therapies”. The author cited statistics from the National Center for Complementary and Alternative Medicine (NCCAM) whose budget is now $1.6 billion. Currently 50% of US residents use some form of alternative medicine and 12% use it for their children.

We are reminded that Hippocrates used leaves from the willow plant to treat headaches and muscle pains; that in the 1800′s the active ingredient of aspirin was isolated, and that quinine from the bark of a cinchona tree was used to treat malaria as early as the 1600′s. Another malaria drug that contains an herb called Artemisia was used by Chinese healers for thousands of years. Clearly these herbs, plants and practices have been important in the development of healing and soothing medications.

The author, however, focuses on some of the expensive studies by the NCCAM that showed failure of efficacy. Apparently $374,000 was spent in an attempt to see if inhaling lemon and lavender scents would promote wound healing (it didn’t), $750,000 to establish whether prayer cures AIDS or hastens recovery from breast reconstruction surgery, $700,000 to investigate whether magnets would treat arthritis, carpal tunnel syndrome or migraine headaches (not proven), and $400,000 to find out if coffee enemas cure pancreatic cancer. (What do you think?) They have also investigated acupuncture and therapeutic touch and, so far, their controlled studies have found that they work no better than placebo. Ah, but “here’s the rub”… Placebos have often been found to alleviate many symptoms and make us feel better. They may “tell” the brain that something is being done and perhaps induce the release of neuromediators that block pain and promote symptom relief.

The author goes on to point out that there are scientists who are avid proponents of the value of negative studies. For example, studies have shown that combination measles-mumps-rubella vaccine does NOT cause autism. But he argues that a negative finding frequently does not change public behavior. There are still many parents who are afraid to vaccinate their children and as a result the rate of pediatric morbidity and mortality from these and other diseases has risen.

When it comes to megavitamins and supplements, there is an ongoing “Why not use it, it won’t hurt” attitude. He points out that several NCCAM-funded studies have shown that garlic does not lower low density lipoprotein cholesterol, ginkgo does not improve memory (I forgot about that one!), St. John’s wort does not treat depression, echinacea and megavitamins do not treat colds. And some studies have shown that megavitamins increase the risk of cancer and heart disease. Vitamins and supplements are not regulated by the FDA.  But these negative data do not seem to negatively impact our need to hope that they work. In 2010, the vitamin and supplement industry grossed $28 billion, up from 4.4% the year before. (I am thinking of having a vitamin of some sort named after me, it might provide a great financial legacy for my kids…just kidding!)

I want to quote the conclusion of the article, it was quite amazing: “Because negative studies performed without a sound biological basis have little or no success, it would make sense for the NCCAM to either refrain from funding therapies that border on mysticism such as distance healing, purging, and prayer; redefine it’s mission to include a better understanding of the physiology of the placebo response; or shift it’s resources to other NIH institutes

I think he makes a good point.

Up to 40% of American’s are sleep deprived. Sleep deprivation has been associated with obesity, hypertension, an increase in inflammatory factors, slow glucose metabolism, impaired insulin sensitivity (both leading to diabetes), depression and elevation of stress hormones such as cortisol, all of which increase the risk for cardiovascular disease (CVD). And we all know about the deleterious effects of inadequate physical activity (both direct and indirect though obesity) on cardiovascular risk factors.  So the question is: if we exercise but still don’t find the time to get adequate sleep, does the exercise still work to ward off coronary vascular disease?

An answer to this query was provided in the April issue of the journal Menopause. The article was titled “Association of leisure physical activity and sleep with cardiovascular risk factors in postmenopausal women”. The authors analyzed 393 participants of the Women on the Move Though Activity and Nutrition Study. (You guessed it, the acronym is WOMAN). This was a 5-year randomized clinical trial designed to test whether an intensive non-medication lifestyle intervention would reduce measures of cardiovascular risk factors.

The women’s physical activity was measured in metabolic equivalents and took into account 39 common, non work (leisure) activities. The women designated as high in leisure time activity were those who had 11.8 or more MET hours per week which was the equivalent of 177 minutes of brisk walking. (That, in case you haven’t done the calculation, comes to a little more than 25 minutes a day.)

The women’s sleep was assessed at 48 months though a sleep questionnaire (the Pittsburgh Sleep Quality Index or PSQI…it seems that the researchers in Pittsburg have been particularly active in sleep science.) The women were asked about sleep quality, duration, how long it took them to fall asleep, sleep disturbance (for example a companion’s snoring or their own), use of sleep medications, daytime drowsiness and habitual sleep efficiency.  Based on their subsequent PSQI, they were given a global score ranging from 0 to 21. A high score indicated poor sleep quality, and scores higher than 5 meant significant sleep disturbance. The National Sleep Foundation recommends adults sleep 7 to 9 hours a night. In this analysis, appropriate sleep time was defined as 7 or more hours a night. Therefore, those women who were classified as good sleepers had a PSQI score of 5 or less and slept at least 7 hours a night. The poor sleepers had a higher PSQI score and slept less than those 7 hours. (I hope you are following this; perhaps you needed more sleep to do so…)

Women in the high-active group had more favorable body mass indexes or BMI’s (think weight for height), narrower waists, lower blood pressure, less low-density lipoprotein (the bad cholesterol), less total body fat, lower insulin and glucose levels than did the women in the low-active group regardless of sleep quality. Even when women in the high active group with poor sleep quality where compared to less active women but who had good sleep quality they still had a lower BMI, waist circumference, and total body fat and insulin level.

Bottom line: Exercise may be more important than sleep when it comes to lowering risk factors for coronary heart disease in postmenopausal women. The authors put it in a slightly more refined and scientific way: “The combined associations of leisure-time physical activity and sleep suggest that cardiovascular risk factors are more favorable in highly active women relative to less active women regardless of sleep.” I’m going out to take a hike, but I also plan to get to bed early, at least tonight!

Links

-->