Acid Inhibitors and Vitamin B-12

     There were many news articles published after a report printed in the Journal of the American Medical Association ( JAMA volume 310, no. 22, pp 2435-2442, December 11, 2013) about the link between stomach acid suppressors and a deficiency of Vitamin B-12.

     Vitamin B-12 is unusual in that it is only found in animal cells, since it is needed to make animal DNA, but not vegetable DNA. Furthermore, the stomach secretes a chemical, called intrinsic factor, which attaches to the Vitamin B-12 molecule and facilitates its absorption by the intestine. As we get older, the stomach secretes less intrinsic factor, so elderly people are more likely to develop a deficiency, which can lead to a reversible anemia, and irreversible neurological defects. 

     Studies in Sweden have shown that if you  swallow enough Vitamin B-12, say 1 mg/day, then you will absorb sufficient vitamin to avoid a deficiency, even in the complete absence of intrinsic factor. So all that a patient on a proton pump acid inhibitor or an H-2 blocker to suppress stomach acid needs to do is to take 1mg/day of Vitamin B-12. The B-12 level should still be checked, but this OTC dose should be sufficient to prevent any problem.

Statins Part 2

     Recently, the American Heart Association and the American College of Cardiology came out with new recommendations for the use of statins. As always, there was no minority report, and some physicians quit the advisory panel because they could not agree with the final recommendations. The important point is that the new recommendations look at patients as more than just their cholesterol numbers.

     The recommendations are quite simple. There is a recommendation for the use of statin therapy based on the patient's medical condition, and there is NO target number to which the total cholesterol or LDL cholesterol should be lowered. Also, Zetia is never recommended since there is no evidence that Zetia, despite lowering cholesterol, can lower the heart attack or stroke risk. There is something that statins do, perhaps related to their anti-inflammatory effect, that does lower these two risks.

     The first recommendation is an emphasis on the Mediterranean diet, which involves increasing one's intake of vegetables, fruits, and whole grains, low fat dairy products, poultry, fish, legumes and nuts, and limiting the intake of sweets, saturated fats, and trans fats.

     High intensity statin therapy is recommended for individuals who have ASCVD and are younger than 75 years, and for those who have had a heart attack. The importance, again, is in prescribing statins, and not aiming for a target number for total cholesterol or LDL cholesterol. Just giving a statin seems to be sufficient to give protection.

     If high intensity statins cannot be tolerated because of muscle cramps, etc., then the dose should be lowered, but in this high risk group, a statin is mandatory.

     If your LDL cholesterol is 190 or higher, then again high dose statin therapy is recommended for any age group.

     If you have diabetes, then moderate intensity statin therapy is recommended between the ages of 40 and 74.

     Using tables which are available in the literature, if your 10 year ASCVD risk is 7.5% or more, and you are between the ages of 40 and 75, then you should be given moderate or high dose statin therapy.

     The overall message is that if you are at risk for a heart attack you should be taking a statin at as high a dose that can be tolerated. Again, the target numbers for cholesterol and LDL cholesterol are no longer used (except that an LDL cholesterol of over 190 should be treated). No longer should an attempt be made to get the LDL down to 70 or 100, etc.

   

   

   

Calcium

     There have been many studies and much written about calcium supplements as well as calcium plus Vitamin D and the amount of calcium in one's diet. There was an excellent review article about these matters recently published in the New England Journal of Medicine (NEJM vol. 369, pp 1537-1543, October 17, 2013) and I thought I would summarize the article here.

     First let me say that the interaction between Vitamin D and calcium is not completely understood. It is also not true that calcium supplements can  reduce age-related bone loss and the susceptibility to fracture, assuming that one has a diet adequate in the RDA of calcium. (One study did show that taking 800 IU of Vitamin D would achieve this goal.) There is therefore insufficient evidence to recommend calcium supplements in community-dwelling adults.

     The RDA of elemental calcium is 1000 mg/day for women up to age 50, and 1200 mg/day thereafter. For men, the RDA is 1000 mg/day up to age 70 and 1200 mg/day thereafter. Most people receive at least this much in their diet. The largest calcium contribution comes from milk and milk products such as yogurt and cheese. The best vegetable for calcium is raw kale, and the best fish is sardines, followed by pink salmon. Another source of calcium is fortified cereals.  Diets containing less than 700 mg/day of calcium can lead to bone loss.

     The recommended upper limits of ingested calcium is 2500 mg/day in women up to age 50 and 2000 mg/day thereafter. For men The same limits apply at the same ages.

     The most common supplements are calcium carbonate (Tums is an example of this) and calcium citrate. Calcium carbonate requires stomach acid to be absorbed, so this pill should be taken with meals, while calcium citrate may be taken at any time. The most common side effect of calcium is constipation and bloating. Some studies show that additional calcium increases your risk of developing kidney stones, and other studies show that it reduces your risk.

     It is important to note that bone meal, oyster shells and dolomite may contain lead, and therefore should not be consumed by pregnant women.

     There was one study showing that calcium supplements can increase one's risk for prostate cancer, and a larger study showing that it did not. There have been studies showing that calcium supplements increase your cardiovascular risk, as well as studies showing that it does not increase your risk, and there has been a good deal of discussion about these conflicting studies. I generally feel that if you have to argue  about the significance of data or a result, then the result is not significant.

   

 

   

   

Exercise is Good For You

     A very interesting meta-analysis was published online in the British Medical Journal by H. Naci (BMJ 2013:347:f5577) this month. It compared the benefits of drug therapy vs.exercise in the secondary prevention of new or worsening conditions in 4 diseases: coronary heart disease, stroke, heart failure, and adult-onset Type II diabetes. They disallowed studies in which both drugs and exercise were prescribed and  because a head-to-head study of exercise vs. drug therapy was the desired goal.

     It is well-known and documented that exercise has health benefits. There is an enhanced quality of life, fewer hospital admissions, and enhanced all-cause mortality in those who exercise. The study here reviewed meta-analyses to try to compare the benefits of drug therapy vs. exercise in mortality.

     The author reviewed 4 sets of patients: those receiving a statin for elevated cholesterol, those receiving a diuretic for chronic heart failure, those receiving anti-coagulation because of a stroke, and those receiving metformin or a similar drug for pre-diabetes. Over 339,000 patients in over 350 meta-analyses were reviewed.  The results can be simply summarized, but should not be taken as a reason to stop medication.

     No difference was found in mortality for secondary prevention of heart disease between drugs and exercise in patients with elevated cholesterol.

     No difference was found in mortality or progression to full diabetes between drug therapy and exercise.

     There was a slight advantage in exercise rather than anticoagulation or anti-platelet therapy in patients with a stroke.

     But diuretics were definitely superior to exercise in patients with chronic heart failure.

     The conclusion would seem to be that if you have any of these four conditions, be sure to start exercising if you are not already doing so, For further details, the full report is available online, whether or not you are a subscriber to the British Medical Journal.

   

   

   

   

Anti-inflammatories, Heart Attacks, and GI Bleeding

          This blog is based on an article that recently appeared in Lancet, vol. 382, pp779-789, Sept. 6, 2013. The article was a meta-analysis (and see my previous blogs on the problems inherent inj meta-analyses) of over 700 studies that looked at the relationship between anti-inflammatory drugs, heart attacks, and GI bleeding. (Recall that Vioxx was taken off the market because of an increase in heart attacks and strokes.)

     A little biochemistry is in order. There are two enzymes released by platelets that synthesize prostaglandins, called COX-1 and COX-2 for short. COX-2 prostaglandins mediate pain and inflammation, and COX-1 prostaglandins protect against GI bleeding, especially in the stomach. Aspirin blocks the production of both enzymes irreversibly, which is why aspirin is used to prevent strokes and reduce pain and inflammation,  and can cause GI bleeding. The studies looked at NSAIDs such as ibuprofen (Advil, Motrin), naproxen (Naprosen, Aleve), and diclofenac. These NSAIDS block both COX-1 and COX-2. The studies also looked at anti-inflammatory drugs such as Celebrex that only blocked COX-2,(called coxibs), and therefore did not increase the risk of GI bleeding.

     The study showed that all NSAIDs increased the risk for GI bleeding, but in no case were acid-blockers such as Prilosec and Prevacid used, which would have decreased the risk. The surprising result was that not only did coxibs increase the risk of heart attacks by one-third, but that all the NSAIDs except Aleve did as well, so that Aleve is the safest from a vascular point of view. Unfortunately, naproxen also had the highest risk of GI bleeding.

     Thus the safest anti-pain and anti-inflammatory drug would appear to be Aleve, but an acid-blocking drug should be taken with it to reduce the risk of GI bleeding.

Men, Testosterone, and Estrogen

     There was an article published recently in the New England Journal of Medicine ( Vol 369, pp1011-1022, Sept. 12 2012) about the effect on men of testosterone and estrogen suppression. It was only a 12 week study, but the results are interesting. I will summarize the study here.

     Firstly, I should mention that the male production of testosterone decreases slowly with age. This actually means that even an "normal" level of testosterone at age 60 is abnormal in the sense that it is diminished from the level at age 20. All men have an enzyme that converts some testosterone to estradiol, an estrogen, and this conversion provides 80% of the circulating estradiol. (I should also mention here that in addition to estrogen and progesterone, all women secrete testosterone.) There are also studies showing that one of the causes of diminished sexual drive in menopausal women is a reduction in their testosterone level, so that estrogen replacement alone may not be enough to restore their sex drive. This was shown initially by a female OB-GYN in Canada.

     The experiment reported in the NEJM showed the effects of chemical castration which eliminated testosterone production. Some of the men also received a drug to inhibit the production of estrogen when the testosterone level was allowed to rise. The results of this climical study can be summarized as follows:

     Testosterone directly regulates lean mass,  muscular strength and sexual function. Testosterone deficiency decreases lean mass, muscle strength, muscle size and sexual function. Low estradiol also contributes to loss of libido and sexual function. Interestingly enough, low estradiol also contributes to increased abdominal fat, and possibly to osteoporosis as well.

     The increase in abdominal fat is medically worrisome, because this increase is associated with resistance to insulin (i.e. to pre-diabetes) as well as the metabolic syndrome. But the solution to low estradiol should not be estrogen replacement, because that was tried with men with prostate cancer and they developed severe cardiovascular problems. 

     The message I take from this study is that after replacing testosterone when necessary, then the estradiol level should be measured. If that level is still low, then the testosterone dose should be increased to normalize the estradiol level and thereby decrease the risk of the patient's developing the metabolic syndrome. It is also trivial to add that menopausal women should have their testosterone level measured. 

    

Mammograms and Breast Cancer

     There has been much confusion and differing recommendations about how often women should get mammograms. Different groups and different countries have different recommendations, all of which are backed by "data". It is very confusing to read all the recommendations and then try to make a decision for oneself.

     The conflict arises, in part, from the difference between making recommendations for one million people and making a recommendation for one individual. If a mammogram shows breast cancer, then the payoff for the individual is 100% in that the breast cancer was detected.All  recommendations from different groups rest, in part, on prior assumptions, so that two groups can look at the same data and arrive at different conclusions.

     Right now the British recommend one mammogram every 3 years between the ages of 50 and 70. The American College of Radiology and the American Cancer society recommend annual mammograms from age 40.  Finally, the US Preventive Services Task Force recommends biannual screenings between the ages of 40 to 74, and the American College of Obstetricians and Gynecologists is not sure if screenings should be annual or biennial. And none of the groups has a  firm recommendation on the benefits of breast self-examination. I should also mention that to my knowledge, no one has compared the possible benefit of a screening mammogram every 6 months vs. once a year.

     The patient should make the decision, of course. With varying recommendations, one will generally pick the one that suits their needs the best. The only caveat is: if a mammogram shows cancer will you blame yourself for not having had one sooner?

     The bugbear is the damage caused by false positive mammograms and unnecessary biopsies. But the people making the recommendations do not, as a rule, discuss false positives with their patients. And the majority of patients would probably risk a negative biopsy in their search for a true one. It
 seems to me that once again we should yield to the patients' views, after outlining the recommendations of the different groups. And I do with that there had been a study comparing semi-annual memmograms with annual mammograms in high risk patients.