Medical Compass

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Mom was right again: Eat your breakfast and your fruits and veggies

Diabetes is always on the medical radar screen. As incidence of the disease continues to grow, there is a constant stream of new research on the topic. One thing you can say definitively about diabetes:  it never gets dull. The American Diabetes Association meeting in June did not disappoint, revealing both good and bad news.

Fortunately, the good news is abundant. Most importantly, mortality decreased 23 percent overall in diabetes patients and 40 percent in diabetics with cardiovascular disease when comparing 2006 and 1997 results, according to a Centers for Disease Control  survey (Diabetes Care June 2012 vol. 35 no. 6 1252-1257). The author of the study warns, however, that diabetics are still at increased risk for severe complications.

Breakfast’s impact

Mothers always struggle to get their children to eat breakfast. In this case, Mom may be onto something. In a study of almost 4,000 participants, ages 27 to 35 years old, those who ate breakfast were less likely to develop type 2 diabetes (ADA June 2012, abstract 1364-P). For each breakfast consumed during the week, there was a 5 percent reduction in risk. When the researchers compared those who ate breakfast at least five times a week to those who ate it three or fewer times a week, the risk of developing type 2 diabetes fell 31 percent among the frequent breakfast eaters. Those who ate breakfast more frequently did not gain as much weight, 0.5 kg/m2. BMI played a role in this effect. This is an easy way to help ward off diabetes, as well as get you charged for the day.

Insulin and cancer

There have been concerns that insulin increases the risk of cancer. However, in three very large epidemiologic studies presented at the ADA meeting, there was no significant association between the use of glargine insulin and an increased risk of cancer, when compared to other insulins (ADA June 2012, abstract CT-SY13).

However, there are caveats to these studies. For instance, why they compared glargine to other insulins and not to oral drugs seems to weaken the study’s conclusions. There were also slight, but non-significant, increases in breast cancer, 12 percent, and prostate cancer, 11 percent, in one of the studies. The studies’ durations were not very long when you consider the length of time it takes to develop cancer. They ranged from 1.2 years to 3.1 years with glargine and 1.1 years to 3.5 years with other insulins. Hence, I think it is important to interpret the results with a bit of skepticism, though they do point in the right direction.

Metformin and B12 deficiency 

Yet another study presented at the ADA found that those diabetes patients who are taking metformin and have B12 deficiencies have a much higher risk of developing peripheral neuropathies (tingling, numbness and pain in the extremities) that may lead to permanent nerve damage (ADA June 2012, abstract 954-P). Chronic metformin use may be a contributing factor to the B12 deficiency. Before attributing the symptoms to diabetic neuropathy, it is important to test patients’ B12 and methylmalonic acid levels. As age increased, not surprisingly, the likelihood of B12 deficiency also increased. For more information on the appropriate levels of B12, please see my May 1, 2012 article.

Fruit and vegetable effect

Those patients who consumed the most fruits and vegetables saw a 21 percent reduction in risk of diabetes, compared to those who consumed the least, according to the EPIC study (Diabetes Care 2012;35(6):1293-1300). Quantity was important with vegetables, showing a 24 percent lower risk in those who ate the most, but quantity did not play a role in fruits. More important to fruit was the variety, with a 30 percent reduction in those with the most diversity in fruit intake. Combining varied fruits and vegetables resulted in the greatest reduction, 39 percent.

Omega-3 Fatty acids

In a recent randomized controlled trial omega-3 (fish oil) supplements showed disappointing results (NEJM online June 11, 2012). Supplementation with 900 mg of omega-3s did not reduce the incidence of stroke, heart disease or death from cardiovascular disease in pre-diabetes or diabetes patients. This dose may be too low, but still it is unlikely that taking omega-3s will reduce the risk of strokes or heart attacks in diabetes patients. I wrote a two-article series, starting on May 22, 2012, that showed omega-3s were effective in some diseases, but not in others. Therefore, there are more efficient ways to treat diabetes than with fish oil.

Thus, the moral of the story is that lifestyle modifications are an important ingredient in preventing and treating diabetes. If you are taking insulin, you can breathe a sigh of relief that it may not increase your risk of cancer. Make sure to test B12 levels, especially if you are taking metformin, and don’t rely on fish oil to prevent complications from diabetes or pre-diabetes. And as my mom always says, eat your breakfast.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management.  For further information, go to the website www.medicalcompassmd.com and/or consult your personal physician.

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A number of diseases respond favorably such as AMD and rheumatoid arthritis

Last week, I shared the depressing news that omega-3 fatty acids from fish and/or fish oil may not have any positive effects in some diseases, such as heart disease, cancer and multiple sclerosis — a surprise to the medical community. However, omega-3s from these sources may be beneficial in other diseases and disorders, including age-related macular degeneration, dry eye, Alzheimer’s, rheumatoid arthritis, diabetes, anxiety and, ironically, depression. So don’t avoid fish or fish oil yet. Talk to your doctor first. Let’s review some of the studies.

AMD effect

In the Women’s Health Study, there was a significant reduction in risk of developing AMD for those women who ate fish on a regular basis (Arch Ophthalmol. 2011;129(7):921-929). AMD is the leading cause of central vision loss or blindness in patients over 55. The great news is that you don’t have to eat a substantial amount of fish — just one serving per week results in a 42 percent reduction in risk. The fish that had most impact included salmon, mackerel, tuna, bluefish, swordfish and sardines.

I would recommend sardines and salmon, which are lower in mercury than the others and higher in omega-3s. In those who were taking fish oil supplements containing docosahexaenoic acid and eicosapentaenoic acid there were significant, though slightly less robust, reductions in the risk of AMD, 38 percent and 34 percent respectively.

This was a large observational study with 39,000 participants and a mean 10 year follow-up duration. The researchers believe that the mechanism of action may have to do with an anti-inflammatory process, since AMD has underlying inflammation.

AREDS 2 is an ongoing five-year randomized controlled trial, the gold standard of studies, that includes fish oil (clinicaltrials.gov). It will be interesting to see if it reinforces these results.

Alzheimer’s disease
Alzheimer’s disease is neurodegenerative disease. There are no medications yet to reverse or slow its progression, only to treat its symptoms. Thus, it is crucial to find lifestyle modifications that may prevent and treat its effects. In a recent study, consumption of omega-3s from fish showed a significant reduction in beta-amyloid protein, a nonspecific marker of Alzheimer’s disease, as measured in the blood (Neurology online May 2).

In another study, consumption of fish at least one time a week showed preservation of brain volume, tested using MRI scans, in the hippocampus and frontal lobe. These areas are responsible for memory and cognitive function.

Both studies are encouraging for Alzheimer’s disease prevention (RSNA Abstract SST11-04). In yet another study, fish oil seemed to reduce the progression of cognitive impairment in patients with very mild Alzheimer’s disease (Arch Neurol. 2006;63:1402-1408).

Rheumatoid arthritis

In the May 24 article, I wrote about a meta-analysis that showed reduction in joint pain and morning stiffness in those who consumed fish oil (Pain. 2007 May;129(1-2):210-23).
These are two of the most common complaints of patients with rheumatoid arthritis.

Diabetes

Omega-3 fatty acids seem to play a role in prevention of type 2 diabetes. In the Cardiovascular Disease Study, there was a 36 percent reduction in the risk of developing diabetes for those who consumed the most omega-3s (Am J Clin Nutr. 2011;94(2):527-33).
The study was unique in that it tested the levels of DHA and EPA in the blood, a quantitative approach, and determined that participants with the highest levels of these omega-3s were least likely to develop the disease.

This was an observational study with 3,000 participants over a 10-year period. These are encouraging results and may indicate another way to reduce diabetes risk.

Dry eye syndrome

The prevalence of dry eye syndrome increases with age and is a common problem, with a higher prevalence among women (Am J Ophthalmol. 2003;136(2):318-26). In the Women’s Health Study, omega-3 fatty acids reduced the risk of dry eye by 17 percent (Am J Clin Nutr. 2005; 82(4):887-93). The omega-3s may work by blocking pro-inflammatory factors in the eye. The best results were found with tuna: one serving per week reduced risk by 19 percent, while two servings reduced risk by a whopping 68 percent. Interestingly, a high omega-6 (pro-inflammatory) to omega-3 ratio increased the risk of dry eye 2.5 times. The typical American diet is low in omega-3s but very high in omega-6s. Included in this latter category are processed foods; meats — especially red meat; dairy such as cheese, whole milk and butter; and certain processed oils. These are foods that are high in fat, but not good fats.
Omega-3s play a potentially significant role in many diseases, but not in all. There is greater upside for omega-3 fatty acids than downside, except as it relates to prostate cancer risk. However, just as with other substances, it may be better to obtain omega-3s from fish than to rely on fish oil. One thing is sure: We get too many omega-6s and not enough omega-3s in our diet and thus may have a higher propensity toward inflammation, which promotes chronic diseases.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, go to the website www.medicalcompassmd.com and/or consult your personal physician.

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Effects are disease dependent: Studies show no benefits in MS and cardiovascular disease

Omega-3 fatty acids are found in many substances, such as fish, supplements and even an approved drug. Fish oil is one of the most frequently used supplements, and we eat fish in the hope that it will prevent chronic diseases. We believed that the effects of omega-3s are beneficial, since they have anti-inflammatory properties and reduce triglycerides (Brit J. Pharmcol. 2008:153:S200-215; Am J Clin Nutr. 2003:77;300-307). But does the research into clinical outcomes confirm this, or is it conjecture?

The answer is complicated, since the effects seem to be disease dependent. On the one hand, omega-3 FAs are beneficial for Alzheimer’s, age-related macular degeneration, dry-eye syndrome, depression, anxiety and rheumatoid arthritis. On the other, omega-3s have no effect in cardiovascular disease, multiple sclerosis or cancer prevention, and may even increase the risk of prostate cancer. Let’s look at the studies.

Cardiovascular disease

The prevailing thought has always been that omega-3s, especially from fish oil, reduce the risk of stroke and heart disease. Unfortunately, one recent study did not show a beneficial outcome for secondary (second event) prevention of cardiovascular disease with supplemental fish oil.

These results were surprising to many in the medical community and went counter to the treatment paradigm. In the Korean Meta-analysis Study Group (a group of 14 randomized clinical trials, the gold standard of studies), the results did not show a reduction in heart attacks, all-cause mortality, sudden cardiac death, transient ischemic attacks or strokes (Arch Intern Med. online April 9, 2012).

In a commentary by a respected researcher at Harvard Medical School, Dr. Frank Hu, these results should be taken in stride — trials for fish oils have shown mixed results in cardiovascular disease. There were also flaws in the Korean meta-analysis: Many of the studies may have been too small, too short in duration and the primary endpoints were not focused on cardiovascular disease.

It will be interesting to see the effects in the VITAL trial, an ongoing primary prevention trial in cardiovascular disease using fish oil plus vitamin D (Contemp Clin Trials. 2012;33(1):159-171).

Right now, the evidence is inconclusive to recommend fish oil for cardiovascular disease. However, fish has benefits that go beyond omega-3s. It is a good source of protein and of astaxanthin, a member of the carotenoid family of phytochemicals (Arch Intern Med. online April 9, 2012).

Effect on cancer

In the SU.FOL.OM3 study, patients who had cardiovascular disease were given fish oil and vitamin B (B6, folate and B12) to reduce the risk of cancer and cancer deaths. The results were disappointing. In fact, with women, the fish oil increased the risk of cancer, though the number of cases was extremely small. It did not matter whether the fish oil was given alone or in combination with B vitamins — the results fell short of expectations (Arch Intern Med. 2012 Apr 9;172(7):540-7).

In a shocker, the Prostate Cancer Prevention Trial, fish consumption actually increased the risk of aggressive prostate cancer by 2.5 times when high levels of DHA (docosahexaenoic acid), an omega-3 FA, were found in the blood. This trial was observational and involved 3,461 men (Am J Epidemiol. 2011 Jun 15;173(12):1429-39). Before jumping to conclusions, know that other studies have shown that omega-3s either had no effect or potentially beneficial effects with prostate cancer (Am J Clin Nutr 2010;92(5):1223-1233).

Regardless, I would not recommend omega-3s to reduce the risk of cancer risk — especially prostate cancer. Those with a family history of high-grade prostate cancer should consult their physician about the risk-benefit ratio of consuming omega-3s in the form of fish and fish oil. This does not have any impact on omega-3s from other sources, such as from nuts and seeds, since these are low in DHA.

Multiple sclerosis
Since omega-3s have supposed anti-inflammatory effects and autoimmune diseases are based on inflammation, it would make sense to assume that multiple sclerosis patients would benefit from fish oil. However, in an RCT, there were no differences in either objective or subjective measures including MRI findings, frequency of relapse, quality of life and fatigue between the groups that took fish oil and not (Arch Neurol. online April 16, 2012).
Researchers even added the standard-of-care medication, interferon beta-1a, to both groups after six months. The only effects seen were from the drug therapy. This was the first RCT in MS with fish oil supplementation, and the size of the trial was small with only 92 patients.
Fish oil supplementation must be undertaken with caution. Does this mean we should avoid fatty fish and fish oils? Not at all. Even in trials with negative results, there are others to counterbalance them.

Next week, I will write about the positive contributions of omega-3s to disease prevention and treatment.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, go to the website www.medicalcompassmd.com and/or consult your personal physician.

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Aspirin and Plavix together are cause for concern in stroke

Last week, I wrote about the positive effects of medications and the complexities that chronic diseases add to the risk profile of stroke. In this article I will focus on the confusion around aspirin’s use in combination with another antiplatelet drug and its ideal preventive dose. Then, I will suggest lifestyle modifications that can help lower stroke risk.

Medication combination: negative impact

There are two antiplatelet medications that are sometimes given together in the hopes of reducing stroke recurrence — aspirin and Plavix (clopidogrel). The assumption was that these medications together would work better than either alone. However, in a randomized controlled trial, the gold standard of studies, this combination not only didn’t demonstrate efficacy improvement, but significantly increased the risk of major bleed and death (ISC 2012; Abstract LB 9-4504; www.clinicaltrials.gov NCT00059306).

Major bleeding risk was 2.1 percent with the combination versus 1.1 percent with aspirin alone, an almost twofold increase. In addition, there was a 50 percent increased risk of all-cause death with the combination, compared to aspirin alone. Patients were given 325 mg of aspirin and either a placebo or 75 mg of Plavix. The study was halted due to these deleterious effects. The American Heart Association recommends monotherapy for the prevention of recurrent stroke. If you are on the combination of drugs, please consult your physician.

Aspirin: low dose vs. high dose

Greater hemorrhagic (bleed) risk is also a concern with daily aspirin regimens greater than 81 mg, which is the equivalent of a single baby aspirin.

Aspirin’s effects are cumulative; therefore, a lower dose is better over the long term. Even 100 mg taken every other day was shown to be effective in trials. There are about 50 million patients who take aspirin chronically in the United States. If these patients all took 325 mg of aspirin per day — an adult dose — it would result in 900,000 major bleeding events per year (JAMA 2007;297:2018-2024). The ideal dose of aspirin to prevent a recurrent stroke is 81 mg.

Lifestyle modifications

On Dec. 20, 2011, I wrote about stroke prevention. A study showed that white fleshy fruits — apples, pears, bananas, etc. — and vegetables — cauliflower, mushrooms, etc. — decreased the risk of ischemic stroke by 52 percent. Not to be left out, the Nurses’ Health study showed that foods with flavanones, found mainly in citrus fruits, decreased the risk of ischemic stroke by 19 percent (Stroke 2012;43:946-951).

The authors suggest that the reasons for the reduction may have to do with the ability of flavanones to reduce inflammation and/or improve blood vessel function. This study involved about 70,000 women with 14 years of follow-up. I mention both of these trials together because of the importance of fruits in prevention of ischemic (clot-based) stroke.

Alcohol’s effect

I am continuously asked about my stand on alcohol consumption. There are definite benefits to drinking alcohol in moderation, and stroke reduction appears to be one. Findings published in March from the Nurses’ Health Study showed a decreased risk of stroke by 17-21 percent in women who consumed between half a glass to one glass of alcohol per day, compared to those who did not (Stroke 2012; 43: 939-945). A serving size is 4 ounces of wine or a 12-ounce beer. This was a very large observational study involving 83,000 women over 26 years.

The authors hypothesize that the effect has to do with improving the lipid profile and/or preventing clot formation. Does this mean if you don’t drink you’re at a disadvantage? Not at all! There are plenty of other lifestyle modifications you can make to reduce your risk equally or more, including eating flavanone-full foods, such as citrus fruits, as well as white fleshy fruits. In addition, the Mediterranean and Dash diets reduce stroke risk. In one recent study, the Mediterranean diet was shown to reduce the risk of ischemic stroke by a resounding 63 percent (J. Nutr. 2011;141(8):1552-1558). Too much alcohol can increase your risk of atrial fibrillation, an arrhythmia that increases stroke risk.

Fiber’s important role

Fiber plays a key role in reducing the risk of a hemorrhagic stroke. In a study involving over 78,000 women, those who consumed the most fiber had a total stroke risk reduction of 34 percent and a 49 percent risk reduction in hemorrhagic stroke. The type of fiber used in this study was cereal fiber, or fiber from whole grains.

Refined grains, however, increased the risk of hemorrhagic stroke twofold (Am J Epidemiol. 2005 Jan 15;161(2):161-9). When eating grains, it is important to have whole grains. Read labels carefully, since some products that claim to have whole grains contain unbleached or bleached wheat flour which are refined.

Fortunately, there are many options to help reduce the risk or the recurrence of a stroke. Ideally, the best option would involve lifestyle modifications. Some patients may need to take statins, even with lifestyle modifications. However, statins’ side-effect profile is dose related. Therefore, if you need to take a statin, lifestyle changes may help lower your dose and avoid harsh side effects. Once you have had a stroke, it is likely that you will remain on at least one medication — low-dose aspirin — since the risk of a second stroke is high.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, go to the website www.medicalcompassmd.com and/or consult your personal physician.

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Age-related macular degeneration, rheumatoid arthritis and some migraines increase risk

I have written on stroke several times, due to the constant flow of intriguing and valuable new studies. On the one hand, it is great to have refinement of treatment paradigms. On the other, unfortunately, stroke remains one of the top five causes of mortality and morbidity in the United States.

Recent studies have involved issues from identifying chronic diseases that increase stroke risk (AMD, RA and migraine) to examining the roles of medications and lifestyle in managing risk.

Impact of chronic diseases

There are several new studies that show chronic diseases — such as age-related macular degeneration, rheumatoid arthritis and migraine with aura — increase the risk for stroke. Therefore, patients with these diseases must be monitored.

AMD study

In the ARIC study, stroke risk was approximately 50 percent greater in patients who had AMD, compared to those who did not — 7.6 percent vs. 4.9 percent, respectively (Stroke online April 2012). This increase was seen in both types of stroke: ischemic (complete blockage of blood flow in the brain) and hemorrhagic (bleeding in the brain). The risk was greater for hemorrhagic stroke than for ischemic, 2.64 vs. 1.42 times increased risk. However, there was a smaller overall number of hemorrhagic strokes, which may skew the results.

This was a 13-year observational study involving 591 patients diagnosed with AMD, ages 45 to 64. Most patients had early AMD. If you have AMD, you should be followed closely by both an ophthalmologist and a primary care physician.

Rheumatoid arthritis

In a recent observational study, patients with RA had a 30 percent increased risk of stroke (BMJ 2012; Mar 8;344:e1257), and those under 50 years old with RA had a threefold elevated risk. This study involved 18,247 patients followed for a 13-year period.

There was also a 40 percent increased risk of atrial fibrillation, a type of arrhythmia or irregular heartbeat. Generally, AF causes increased stroke risk, however, the authors were not sure if AF contributed to the increased risk of stroke seen here. They suggested checking regularly for AF in RA patients, and they surmised that inflammation may be an underlying cause for the higher number of stroke events.

Migraine with aura

In the Women’s Health Study, an observational study, the risk of stroke increased by twofold in women who had migraine with aura (Neurology 2008 Aug 12; 71:505). Only about 20 percent of migraines include an aura, and the incidence of stroke in this population is still rather rare, so put this in context (Neurology. 2009;73(8):576).

As I mentioned in my previous article on migraine, there are studies, as well as anecdotal stories showing diet plays a significant role in preventing and decreasing the frequency of migraine.

Medications with beneficial effects

There are two medications recently that have shown positive impacts on reducing stroke risk: statins and valsartan. Statins are used to lower cholesterol and inflammation, and valsartan is used to treat high blood pressure.

Statins have received bad press recently due to their risks of side-effects, such as diabetes, cognitive impairment and myopathy (muscle pain). However, used in the right setting, statins are very effective. In one study, there was reduced mortality from stroke in patients who were on statins at the time of the event (AAN conference: April 2012). Patients who were on a statin to treat high cholesterol had an almost sixfold reduction in mortality compared to those with high cholesterol who were not on therapy.

There was also significant mortality reduction in those on a statin without high cholesterol, but with diabetes or heart disease. The reason for the latter result is not clear, so we should not jump to conclusions, especially since the study is only published in abstract form.

The authors surmise that this result might be from an anti-inflammatory effect of the statins. Of course, if you have side effects, you should contact your physician immediately.

Valsartan is an angiotensin II receptor blocker that works on the kidney to reduce blood pressure. However, in the post-hoc analysis (looking back at a completed trial) of the Kyoto Heart Study data, valsartan used as an add-on to other blood pressure medications showed a significant reduction, 41 percent, in the risk of stroke and other cardiovascular events for patients who have coronary artery disease (Am J Cardiol 2012; 109(9):1308-1314).

It is important to recognize that chronic disease increases stroke risk. High blood pressure and high cholesterol are two of the most significant risk factors. Fortunately, statins are an effective way to reduce cholesterol, and valsartan may be a valuable add-on to prevent stroke in those patients with coronary artery disease.

Next week, we will continue our discussion of medications, exploring a surprising finding with combination therapy and the effects of lifestyle modifications.

This is part one of a two-part series on strokes.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, go to the website www.medicalcompassmd.com and/or consult your personal physician.

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It is important to check MMA blood levels and supplement with B12 where needed

I am not a big believer in supplements, unless they are used to treat a proven deficiency. However, we may be deficient in vitamin B12 (cobalamin) without knowing it. Contradictory recommended levels of B12 across the world, the lack of sensitivity in B12 deficiency tests and confusing symptoms all add to the complexity of diagnosing and treating it.
B12 is an integral part of many of the body’s systems. For example, B12 plays a role in proper immune system functioning (www.medscape.com).

What are the symptoms of B12 deficiency?

Symptoms of B12 deficiency include fatigue, diarrhea or constipation, exercise-induced shortness of breath and neurological deficits, such as difficulty concentrating, memory problems and paresthesias (tingling and numbness in the appendages) (Geriatrics. 2003 Mar;58(3):30-4, 37-8). However, these symptoms can mimic many different diseases. Typically, physicians test for B12 and anemia levels when symptoms occur. However, approximately half of those with B12 deficiency are in the “normal” range (Am Fam Physician. 2003 Mar 1;67(5):979-986). To add to the complexity, early B12 deficiency may be asymptomatic.

Minimum blood levels of B12

Unfortunately, there is no worldwide consensus on minimum acceptable B12 levels. Other countries, such as Japan, have significantly higher recommended levels than the United States.

In Japan, minimum recommended blood levels of B12, 500 pg/ml (Jpn. J. Psychiatry Neurol. 1988 Mar:42(1):65–71), are more than twice the minimum acceptable levels in the U.S., 200 pg/ml (www. nlm.nih.gov). There are those who suggest U.S. B12 recommended levels are too low (J Am Geriatr Soc 1996 Oct;44(10):1274–5). If we were to follow Japanese guidelines, we would still be far below the upper limit of the U.S. recommended range.

Diagnostic tests to avoid deficiency

B12 blood levels may not be the most accurate test for determining deficiency (Proc Nutr Soc. 2008 Feb;67(1):75-81). There is a much more specific blood test: methylmalonic acid (MMA). If this level is high, then it is a reliable indicator that B12 levels are low (Subcell Biochem. 2012;56:301-22). Deficient levels of B12 lead to increased MMA levels, since MMA requires B12 to metabolize (Am Fam Physician. 2003 Mar 1;67(5):979-986). Both B12 and MMA levels should be checked.

Who needs to have their levels monitored?

The elderly should be tested regularly, but surprisingly people from young adulthood to middle age can also be affected. The Framingham Offspring Study found that more young adults may be affected than thought previously (Am J Clin Nutr. 2000;71:514-22). Interestingly, those in three different age groups ranging from 26 to 65 years old and older were impacted similarly (Am Fam Physician. 2003 Mar 1;67(5):979-986).

When I attended the Harvard-Brigham and Women’s CME program, we went over a B12 deficiency case in the aptly named “Can’t Miss Diagnoses” seminar. The case involved a 40-year-old woman with symptoms of tingling in her right foot. Her B12 levels were 250 pg/ml — the low end of normal. Three months later, she complained of being tired, having memory problems plus tingling in both feet. Her labs showed no anemia. Five months later, her MMA levels were checked; they were abnormally high. She was given B12 injections and her symptoms diminished.

What causes B12 deficiency?
Sixty to 70 percent of the time, B12 deficiency is caused by absorption issues (CMAJ. 2004;171(3):251–259). Affected populations include those taking medications, such as Glucophage (metformin) and proton pump inhibitors (PPIs); those who have autoimmune diseases, such as pernicious anemia or Crohn’s disease; alcoholism; and those who have had bariatric surgery (www.ncbi.nlm.nih.gov).

PPIs impact

The reason that proton pump inhibitors such as Protonix (pantoprazole), Nexium (esomeprazole) and Prevacid (lansoprazole) reduce B12 absorbed from diet is that acid in the stomach is required to free B12 from protein molecules in food. PPIs reduce this much-needed pepsin (acid). Therefore, those on PPIs should be monitored for B12 deficiency. It can take approximately three years of continuous use before someone becomes deficient (Aliment Pharmacol Ther. 2008 Jun 1;27(11):1110-21).

Treatments

The amount of B12 absorbed is limited. In a dose of 500 mcg of B12, only 10 mcg are actually absorbed (Blood 2008;112:2214-21). Unless patients have significant symptoms, it may be best to give oral B12 supplements to patients who have high MMA levels and/or low “normal” B12 levels.

One recommendation for B12 oral treatment is 1000 to 2000 mcg daily for one week and then 1000 mcg daily for maintenance (JAMA. 1991;265:94–5). For those with significant symptoms, B12 injections may be preferable.

Dietary sources

Foods with the most B12 are fish and seafood, as well as meat and dairy. This means that those who focus on a primarily vegetable-based diet require B12 supplementation.

Don’t wait until symptoms are severe. Have your B12 blood levels and MMA levels checked, regardless of your age. Symptoms, including peripheral neurologic symptoms, are potentially reversible if treated early.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, go to the website www.medicalcompassmd.com and/or consult your personal physician.

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Commonly used medications, both prescription and OTC, may have deleterious effects on vision

When we refer to adverse events with medications, we usually focus on systemic consequences. However, we rarely address the fact that eyes can be adversely affected by medications. There have been several studies recently that illustrate this very important point.

It is vital that we recognize the symptoms of eye distress. Some of these may indicate ophthalmic emergencies. The medications recently studied include common therapeutics, such as bisphosphonates, aspirin, a class of antibiotics called fluoroquinolones and a migraine therapy. I will explain the symptoms to be cognizant of with each.

The impact of bisphosphonates

The class of drugs known as bisphosphonates is the mainstay for the prevention and treatment of osteoporosis. Recent adverse news focused on atypical femur fractures and osteonecrosis (death of part of the jawbone), not on an ocular effect. However, in a large retrospective study (looking at past data), oral bisphosphonates were shown to increase the risk of uveitis and scleritis, both inflammatory eye diseases, by 45 percent and 51 percent respectively (CMAJ. 2012 Apr 2. [Epub ahead of print]). One out of every 1,100 patients treated with the drugs suffered from uveitis, and one out of every 370 patients treated suffered from scleritis.

Why is this important? The consequences of not treating uveitis can lead to complications, such as glaucoma and cataracts. The symptoms of uveitis typically include eye redness, pain, light sensitivity, decreased vision and floaters (www.mayoclinic.org).

For scleritis, the symptoms are severe pain that radiates to the face and around the orbit, with worsening in the evening and morning and with eye movements (www.uptodate.com). Uveitis affects the iris and ciliary body (fluid inside the eye and muscles that help the eye focus), while scleritis affects the sclera, or white part of the eye.

These adverse eye events occurred only in first-time users. The authors believe the mechanism of action may involve the release of inflammatory factors by the bisphosphonates.

Aspirin yet again?

It seems aspirin can never get a break. It has been implicated in gastrointestinal bleeds and hemorrhagic (bleeding) strokes. Now the European Eye Study suggests that aspirin increases the risk of age-related macular degeneration (Ophthalmology. 2012;119:112-118). The primary effect is seen, unfortunately, with wet AMD, which is the form that leads to central vision loss. The risk of wet AMD is directly related to the frequency of aspirin use. When aspirin is used at least once a week, but not daily, the risk is increased by 30 percent. When it is used daily, the risk of wet AMD jumps to 226 percent. Aspirin also increased the risk of early AMD.

This study was large and retrospective in design, and it included fundoscopic (retinal) pictures, making the results more reliable. The authors recommend that AMD patients not use aspirin for primary prevention, meaning without current cardiovascular disease. However, aspirin use for secondary prevention — for those with heart disease or a previous stroke — the benefits of the medication outweigh the risks.

The role of antibiotics: fluoroquinolones in retinal detachment

Fluoroquinolones may have toxic effects on the synthesis of collagen and on connective tissue, potentially resulting in retinal detachments and Achilles tendon rupture. This is a common class of antibiotics used to treat acute diseases, such as urinary tract infections and upper respiratory infections.

In a recent epidemiologic study, these drugs were shown to increase the risk of retinal detachment by 4.5 times (JAMA. 2012;307:1414-1419). Common fluoroquinolones include ciprofloxacin (Cipro), levofloxacin (Levaquin) and gatifloxacin (Tequin).
Although it sounds like an impressive number, it’s not a common occurrence. It takes the treatment of 2,500 patients before one patient is harmed. Also, this was only noticed in current users, not in recent or past users. However, it is a serious condition.

Retinal detachment is an ophthalmic emergency, and patients need to be evaluated by an ophthalmologist urgently to avoid irreparable damage and vision loss. Retinal detachments are treatable with surgery. Best results are seen within 24 hours of symptoms, which include many floaters, bright flashes of light in the periphery and a curtain over the visual field (www.ncbi.nlm.nih.gov). Fortunately, retinal detachments usually only affect one eye.

Migraine medication

Topiramate (Topomax) is a drug used to treat and prevent migraines. In a recent case-control (with disease vs. without disease) study, topiramate increased the risk of glaucoma in current users by 23 percent. The risk more than doubled to 54 percent in first-time users (Am J Ophthalmol. 2012 May;153(5):827-30). The mechanism of action may be related to the fact that topiramate increases the risk of intraocular pressure.

It is important to be aware that medications not only have systemic side effects, but ocular ones as well. Many of these medications cause adverse effects that require consultation with an ophthalmologist. If you have ocular symptoms related to medications, contact your physician immediately.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, go to the website www.medicalcompassmd.com and/or consult your personal physician.

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Rheumatoid arthritis is one of many autoimmune diseases, where the body’s immune system begins to attack the body’s own tissue. RA results in systemic (throughout the body) inflammation which initially affects the synovium (lining) of the small joints in both the hand and the feet bilaterally, as well as the wrists and ankles (www.ncbi.nlm.nih.gov). It causes pain, stiffness and swelling of the joints.

RA, like most autoimmune diseases, affects significantly more women than men (www.mayoclinic.com) and can be incredibly debilitating. It affects approximately 1 percent of the U.S. population (Arthritis Rheum. 2008;58:15-25). Fortunately, treatments have helped to significantly improve sufferers’ quality of life.

RA may be treated initially with acetaminophen and NSAIDs (such as ibuprofen), depending on its severity. To help stop progression and preserve the joints, disease modifying anti-rheumatic drugs (known as DMARDs) may be used. They are considered the gold standard of treatment for RA and include methotrexate, which has been around the longest and is a first-line therapy; plaquenil (hydroxycholorquine); and TNF inhibitors, such as Enbrel (etanercept), Humira (adalimumab) and Remicade (infliximab).

DMARDs work by reducing inflammation and acting as immunosuppressives, basically tamping down or suppressing the immune system. These drugs have helped RA patients improve their quality of life, preserving joint integrity and causing RA to go into remission.

The downside of using immunosuppressive drugs

Unfortunately, DMARDs have significant adverse effects. They include black-box warnings of serious or life-threatening side effects, such as opportunistic infections — more likely in combination with other immunosuppressives — and malignancy.

Anecdotally, I recently had a patient who had previously developed pneumonia twice, multiple basal-cell carcinomas and one episode of melanoma. These were attributed to use of a TNF inhibitor.

Skin cancer risk

In 2009, the FDA warned that there is an increased risk of cancer after about 30 months of treatment, especially with TNF inhibitors. A 2011 meta-analysis (a group of 28 studies) found that TNF inhibitors may increase the risk of cancers, including skin cancers (Ann Rheum Dis. 2011 Nov;70(11):1895-904). In four of the studies, there was a 45 percent elevated risk of developing skin cancer other than melanoma. However, in data pooled from two of the studies, there was a 79 percent greater chance of developing melanoma. All the studies in this analysis were observational studies, and the absolute risk of developing cancer is small. The good news is that this analysis did not appear to show increased risk of lymphoma.

Complications from RA

RA can also affect organs and the surrounding tissue. Thus, complications from RA include heart disease, stroke, atrial fibrillation, chronic obstructive pulmonary disease, fracture risk, as well as uveitis and scleritis (inflammatory disorders of the eye).

Cardiovascular disease

Patients with RA are at a threefold increased risk of developing coronary artery disease, compared to the general population (Ann Rheum Dis. 2007;66(1):70). Those RA patients who stopped taking statins for high cholesterol and/or heart disease, had a 60 percent increased risk of cardiovascular mortality and a 79 percent increased risk of all-cause death after three months (Arthritis Care Res [Hoboken]. 2012 Mar 29). Though statins have their pitfalls, they can be potentially lifesaving in the right context. Don’t discontinue statins before consulting your physician.

Non-pharmacologic approaches

Exercise and fish oil have shown reductions in symptomatology and joint inflammation. In a meta-analysis (a group of 17 trials), omega-3 fish oil reduced joint pain intensity, as reported by patients, minutes of morning stiffness, number of painful joints and NSAID use significantly (Pain. 2007 May;129(1-2):210-23). The dose was at least 2.7 g of EPA plus DHA in the omega-3 fish oil and took at least 12 weeks of treatment to see a benefit.

Exercise is also important to relieve joint pain and stiffness. In a meta-analysis of 14 studies, there was a 69 percent reduction in pain with aerobic exercise (Br J Sports Med. 2011;45(12):1008-1009). Understandably, however, a study found that 42 percent of RA patients don’t work out at the recommended minimum of 10 minutes of moderate exercise daily (Arthritis Care Res [Hoboken]. 2012 Apr;64(4):488-93). The reasons were that half were either not motivated or believed that exercise had no benefit.

Prevention

In the Iowa Women’s Health Study, results showed that supplemental vitamin D decreased the risk of RA by 34 percent (Arthritis Rheum. 2004 Jan;50(1):72-7). This study involved almost 30,000 women followed over an 11-year period.

The best way to treat an autoimmune disease like rheumatoid arthritis is to prevent it with an anti-inflammatory diet, exercise and omega-3 fish oil. Barring that, however, it is encouraging that DMARD treatments may be effective at half the dose once the disease has been suppressed significantly. Therefore, a low-dose pharmacological approach coupled with non-pharmacological lifestyle adjustments may produce the best outcomes with the fewest adverse reactions.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, go to the website www.medicalcompassmd.com and/or consult your personal physician.

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Dehydration is a topic that is often overlooked or is given only cursory thought, but it’s very important. Dehydration is simple to avoid, right? Not necessarily. We may be dehydrated prior to experiencing symptoms of thirst. With summer right around the corner, especially with this year’s above-average temperatures, this seems an appropriate topic. Complications and symptoms of dehydration can be mild to severe, ranging from constipation, mood changes, headaches and heart palpitations to heat stroke, migraines and heart attacks.

Effect on headaches and migraines

Temperature is a potential trigger for headaches and migraine. As the temperature rises by intervals of 9 degrees, the risk for headache and migraines increases by 8 percent (Neurology. 2009 Mar 10;72(10):922-7). This study involved 7,054 participants from one emergency room site. Warmer temperatures can potentially reduce blood volume in the body, causing dilation of the arteries, resulting in higher risk of headaches and migraines.

In another study, those who drank four cups more water had significantly fewer hours of migraine pain than those who drank less (Handb Clin Neurol. 2010;97:161-72). Headache intensity decreased as well. Anecdotally, I had a patient recently who experienced a potentially dehydration-induced migraine after playing sports in the sweltering heat of Florida. He had the classic aura and was treated with hydration, tylenol and caffeine, which helped avoid much of the suffering.

The impact on heart palpitations

Heart palpations are very common and are broadly felt as a racing heart rate, skipped beat, pounding sensation or fluttering. Dehydration and exercise are contributing factors (my.clevelandclinic.org). They occur mainly when we don’t hydrate prior to exercise. All we need to do is drink one glass of water prior to exercise and then drink during exercise to avoid palpitations. Though these are not usually life threatening, they are anxiety producing for patients.

Heart attacks

The Adventist Health Study, an observational study, showed a dose-response curve for men (Am J Epidemiol 2002 May 1; 155:827-33). In other words, group one, which drank more than five glasses of water daily, had the least risk of death from heart disease than group two, which drank more than three glasses of water daily. Those in group three, which drank less than two glasses per day, saw the least amount of benefit, comparatively. For women, there was no difference between groups one and two; both fared better than group three.

The reason for this effect, according to the authors, may relate to blood or plasma viscosity (thickness) and fibrinogen (a substance that helps clots form).

Mood and energy levels

In a recent study, mild dehydration resulted in decreased concentration, subdued mood, fatigue and headaches in women (J. Nutr. February 2012 142: 382-388). In this small study the mean age of participants was 23, and they were neither athletes nor highly sedentary. Dehydration was caused by walking on a treadmill with or without taking a diuretic (water pill) prior to the exercise. The authors concluded that adequate hydration was needed, especially during and after exercise.

I would also suggest, from my practice experience, hydration prior to exercise.

Different ways to remain hydrated

Now we realize we need to stay hydrated, but how do we go about this? How much water we need to drink depends on circumstances, such as diet, activity levels, environment and other factors. It is not true necessarily that we all should be drinking eight glasses of water a day. In a recent review article, the authors analyzed the data, but did not find adequate studies to suggest that eight glasses is supported in the literature (AJP – Regu Physiol. 2002;283:R993-R1004). It may actually be too much for some patients.

You may also get a significant amount of water from the foods in your diet. Nutrient-dense diets, like the Mediterranean or DASH, have a plant-rich focus. A study mentions that diets with a focus on fruits and vegetables increases water consumption (Am J Lifestyle Med. 2011;5(4):316-319). As you may know, 95 percent of their weights are attributed to water. An added benefit is an increased satiety level without eating calorically dense foods.

The myth: Coffee is dehydrating

In a recent review, it was suggested that caffeinated coffee and tea don’t increase the risk of dehydration, even though caffeine is a mild diuretic (Exerc Sport Sci Rev. 2007;35(3):135-140). With moderate amounts of caffeine, the liquid has a more hydrating effect than the diuretic effect.

Thus, it is important to stay hydrated to avoid complications — some are serious, but all are uncomfortable. Diet is a great way to ensure that you get the triple effect of high amount of nutrients, increased hydration and sense of feeling satiated without calorie-dense foods. However, don’t go overboard with water consumption, especially if you have congestive heart failure or open-angle glaucoma (Br J Ophthalmol. 2005:89:1298–1301).

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, go to the website www.medicalcompassmd.com and/or consult your personal physician.

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Alcohol: weighing the risks versus the benefits

There is much confusion over whether alcohol is beneficial or detrimental to your health. The short answer is: It depends on your circumstances, including your family history and consideration of diseases you are at high risk of developing. Alcohol is one of the most widely used over-the-counter drugs.

Several new studies have been published, some touting alcohol’s health benefits with others warning of its risks. The diseases addressed by these studies include breast cancer, heart disease and stroke. It is important that context becomes the determining factor for alcohol intake.

Breast cancer impact

In a meta-analysis (group of 113 studies), there was an increased risk of breast cancer with daily consumption of alcohol (Alcohol and Alcoholism: published online March 29). The increase was a modest but statistically significant 4 percent, and the effect was seen at less than one drink per day. The authors warned that women who are at high risk of breast cancer should not drink alcohol or should drink it only occasionally.

It was also shown in the Nurses’ Health Study (an observational study) that drinking three to six glasses per week increases the risk of breast cancer modestly over a 28-year period (JAMA. 2011;306:1884-1890).

This study involved over 100,000 women. Even a half-glass daily of alcohol was associated with a 15 percent elevated risk of invasive breast cancer. The risk was dose-dependent, with one to two drinks per day increasing risk to 22 percent, while those having more than drinks per day had a 51 percent increased risk.

A drink several times a week may have the least impact on breast cancer, if you are going to consume alcohol. According to an accompanying editorial, alcohol may work by increasing the levels of sex hormones, including estrogen, and we don’t know if stopping diminishes the effect, although it probably does (JAMA. 2011;306(17):1920-1921).

Stroke effects

On the positive side, the Nurses’ Health Study demonstrated a decrease in the risk of both ischemic strokes (caused by clots) and hemorrhagic strokes (caused by bleeding) with low to moderate amounts of alcohol (Stroke: published online March 8). This analysis involved 83,578 women. Those who drank less than 0.5 glasses of alcohol daily were 17 percent less likely than nondrinkers to experience a stroke. Those who consumed 0.5 to 1.5 glasses a day had a 21 percent decreased risk of stroke, compared to nondrinkers.

However, women who consumed more experienced a decline in benefit, and drinking more than three glasses resulted in a nonsignificant increased risk of stroke. The reasons for alcohol’s benefits in stroke have been postulated to involve an anti-platelet effect (preventing clots) and increasing HDL (“good”) cholesterol. Patients shouldn’t drink alcohol solely to get the stroke protection benefits.

Heart effect

In the Health Professionals follow-up study, there was a substantial decrease in the risk of death after a heart attack from any cause, including heart disease, in men who drank moderate amounts of alcohol compared to those who drank more or were nondrinkers (Eur Heart J: published online March 28).

Those who drank less than one glass experienced a 22 percent reduction in risk, while those who drank one to two glasses saw a 34 percent reduction in risk. The authors mention that binge drinking negates any benefits. This study has a high durability spanning 20 years.

Alternative to alcohol for nondrinkers or in addition to alcohol for drinkers

An analysis of the Nurses’ Health Study recently showed that those who consumed more citrus fruits had approximately a 19 percent reduction in the risk of stroke (Stroke: published online Feb. 23). These results were similar to the reduction seen in the Nurses’ Health Study with modest amounts of alcohol.

The citrus fruits used most often in this study were oranges and grapefruits. Of note, grapefruit may interfere with medications such as Plavix (clopidogrel), a commonly used anti-platelet medication to prevent strokes (www.medscape.com). Grapefruit inhibits the CYP3A4 system in the liver, thus increasing the levels of certain medications.

Alcohol in moderation

Moderation is the key with alcohol. It is very important to remember that alcohol is a drug that has side effects, such as insomnia. The American Heart Association recommends that women drink up to one glass a day of alcohol.

I would say that less is more. To get the stroke benefits and avoid the increased breast cancer risk, half a glass of alcohol per day may be the ideal amount.

Moderate amounts of alcohol for men are up to two glasses daily, though one glass showed significant benefits. Remember, there are other ways of reducing your risk of these maladies that don’t require alcohol.

If you like to drink, it doesn’t mean you can’t and you can even garner advantages for your health. However, don’t force yourself to drink.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, go to the website www.medicalcompassmd.com and/or consult your personal physician.