Vaccine Against Tuberculosis Might help MS

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By W. Wlassoff, PhD

An interesting and rather intriguing finding was published recently by the researchers from Sapienza University in Rome. The scientists have found that a vaccine against tuberculosis can be used to prevent the onset of multiple sclerosis.

Multiple sclerosis (MS) is one of the common diseases affecting the nervous system. It causes problems with muscle movement, balance and vision. Once the first symptoms of MS appear, the disease tends to develop in the next few years. Approximately half of the patients develop MS within two years after their first symptoms. Only 10% of patients do not have any further problems. We currently don’t have effective methods for the treatment or prevention of this disease. The condition can be a significant burden for affected individuals and their families.

The anti-tuberculosis BCG vaccine is one of the most common TB-preventing treatments. It was invented 80 years ago and has proven to be safe. In the experiments of Italian scientists, it turned out that providing the BCG vaccine to people with the first symptoms of MS significantly reduced their chances of developing full-scale multiple sclerosis in future years.

Tuberculosis vaccine stimulates immune system to fight multiple sclerosis

Researchers have done a small clinical trial on a group of 33 patients with the first signs of MS. It turned out that 58% of the patients vaccinated with BCG vaccine remained MS-free after 5 years. Only 30% of patients who did not receive the vaccine were disease-free after this period of time.

Scientists believe that the effect of TB vaccine works on the level of the immune system. Vaccination stimulates the natural immune system to work more efficiently which can help in preventing the development of MS. The experiment confirms the view that exposure to some infections earlier in life helps to develop a stronger immune system more capable of protecting the body from other dangers.

Summary

A commonly used TB vaccine had a surprising effect on people with early stages of multiple sclerosis. TB immunization at the first signs of MS helped to prevent the development of disease in more than half of the immunized patients.

Reference

  1. Giovanni Ristori, Silvia Romano, Stefania Cannoni et al. Effects of Bacille Calmette-Guérin after the first demyelinating event in the CNS. Neurology.

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Vitamin D-The Facts

Vitamin D: The Facts

Vitamin D plays an important role in several bodily functions.  This vitamin is fat soluble and has been at the center of attention in recent years. Vitamin D helps bones in absorbing calcium in the small intestines and is essential for bone growth and maintaining bone density. This vitamin is believed to have some role in the prevention of cancer, autoimmune conditions, heart disease, infections, and a number of other conditions.(1)

Main sources of vitamin D

1)      Vitamin D2 or ergocalciferol: is absorbed through food.

2)      Vitamin D3 or cholecalciferol: synthesized in the skin by ultraviolet B (UV-B) rays from the sun.

Which vitamin D is the better one?

Several studies have suggested that vitamin D 3 is absorbed better and is more efficient in increasing and maintaining the blood vitamin D level.(2)

Diagnosis

The best way to diagnose vitamin D deficiency is to measure 25 (OH)-D and not 1, 25 (OH)-D. This is an important point that sometimes is overlooked. The half-life of 25(OH)-D is 2 to 3 weeks, and for 1, 25(OH)2-D it is only 4 hours. This is one of the reasons why 1, 25(OH)2-D is not a good indicator of vitamin D deficiency. .25(OH)-D is the major circulating form of vitamin D. There is some degree of concern about the accuracy and dependency of current available essays for measuring vitamin D. Therefore the interpretation of these values should be done with caution.

Vitamin D consumption in United States

Most Americans according to the data from NHANES population consume between 272-396 IU  of Vitamin D daily.

Foods with the highest content of vitamin D in IU

Food Vitamin   D content in IU
Dried   shitake mushrooms (non-radiated) 1660/100   g
Atlantic   herring (raw) 1628/100   g
Canned pink salmon   with bones in oil 624/100 g
Fortified   orange juice/soy milk/rice milk 400/L
Canned   tuna/sardines/salmon/mackerel in oil 224–332/100   g
Shrimp 152/100   g
Yogurt   (normal, low fat, or nonfat) 89/100   g
Swiss   cheese 44/100   g
Cereal   fortified 40/serving

Adapted from United States Department of Agriculture

Vitamin content in breast milk

The Vitamin D content of breast milk is inadequate to satisfy the suggested daily consumption of vitamin D and averages ?22 IU/L (range: 15–50 IU/L) in a well-nourished mother.(3)

Amount of body necessary to be exposed to sun

According to studies, at least 20% of the body’s surface should be exposed to UV-B.  Wearing white cotton that transmits more UV-B to the body is better than black wool for blood vitamin D concentrations to increase. Additionally, sunscreen could reduce the absorption of UV-B and consequently cause a lower level of 25-OH-D. For instance, sunscreen with a sun protection factor (SPF) of 8 can decrease vitamin D3 synthetic capacity by 95%, and SPF 15 can decrease it by 98%.

How much daily intake of vitamin D is required?

T h e E n d o c r i n e S o c i e t y’s- Clinical Guidelines

Infant and children 0-1year 400 IU/ daily
Children 1 year and older 600 IU/ daily
Adults 18-50 year 600 IU/ daily
Adults 50-70 year 600-800 IU/daily
Pregnant women At least 600 IU/daily
Patients on seizure medications,steroids, antifungals such as ketoconazole,   andmedications for AIDS at least two to threetimes more vitamin D for their age group

http://www.endo-society.org/guidelines/final/upload/final-standalone-vitamin-d-guideline.pdf

Institute of Medicine Guidelines

Infants 0-12 months No recommendations
Infant and children 1-18 year 600 IU/ daily
Adults 18-70 year 600 IU/ daily
Adults older than 70 year 800 IU/ daily
Pregnant women 600 IU/daily

Summary

Vitamin D has shown to be an important part of many required functions of the body and therefore, maintenance of a healthy level is essential. The accuracy of vitamin D level measurement throughout the country has been limited and is a cause of concern. Hopefully, with usage of better techniques the accuracy and reliability of these tests will also improve. There have been confusing recommendations from different organizations about the amount of vitamin D necessary to avert deficiency in recent years, including the recent U.S. Preventive Services Task Force conclusion that the benefits and harms of daily supplementation with greater than 400 IU of vitamin D3and greater than 1,000 mg of calcium to prevent fractures are not clearly understood.

In my opinion, the guidelines from the Endocrine Society and Institute of Medicine are not very different from each other.  The Endocrine Society’s recommendations are slightly more specific. Therefore, I would suggest following these recommendations at this time until more data is available. It is also important to mention that overuse of vitamin D may cause more harm than resulting in any additional benefits and should be discouraged.

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Reference

  1.  Holick MF2007 Vitamin D deficiency. N Engl J Med 357:266–281 CrossRefMedline
  2. Trang HM, Cole DE, Rubin LA, Pierratos A, Siu S, Vieth R. Evidence that vitamin D3increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2. Am J Clin Nutr. 1998;68 (4):854– 858 Abstract
  3. Leerbeck E, Sondergaard H. The total content of vitamin D in human milk and cow’s milk. Br J Nutr. 1980;44 (1):7– 12 CrossRefMedlineWeb of Science
Coq10-Coenzyme Q10 review

A Review and Analysis of Coenzyme Q10 (CoQ10)

Coq10-Coenzyme Q10 review

The number of individuals who take Coenzyme Q10 (CoQ10) supplements has been steadily increasing. CoQ10 has been suggested for treatment of a variety of disorders, in particular high blood pressure and statin-induced muscle pain. In this article I would like to discuss the available literature about CoQ10 with a view to answering the question, “Do we have enough evidence that CoQ10 works and that the benefits of taking this supplement justify its significant cost?”

CoQ10 is a potent antioxidant, a membrane stabilizer, and an essential cofactor in the mitochondrial respiratory system, helping to generate adenosine triphosphate (ATP), the main energy source for cells. It is found in all human cells, with the highest concentrations in the heart, liver, kidney, and pancreas. CoQ10 was first isolated from beef heart mitochondria by Frederick Crane of Wisconsin, USA, in 1957. CoQ10 is almost always measured by high performance liquid chromatography (HPLC). CoQ10 is fat soluble and transported in lipoprotein particles in the circulatory system. It has been positively correlated with plasma total cholesterol and Low Density Lipoprotein-cholesterol (LDL-C).

Research studies have shown that plasma CoQ10 is reduced by statins (cholesterol-reducing medication). Both CoQ10 and statins are synthesized by the mevalonate pathway. According to some reports, following statin therapy, the reduction can be up to 54% in plasma/serum CoQ10 concentrations.

Reference Interval

The adult reference interval for plasma/serum CoQ10 is approximately 0.5 – 1.7 ?mol/L. Because the plasma CoQ10 level is strongly correlated with lipid level concentration, it has been suggested that the ratio of CoQ10 to total or LDL-cholesterol should be reported.

Different CoQ10 Supplements

Different brands of CoQ10 supplements are currently available on the market; however, due to a lack of standardization, the formulation of these supplements can be significantly different. The variability of supplements and their bioavailability is based on whether they are dry powder capsules or dispersed in oil. Furthermore, significant variability has been seen in the absorption of CoQ10 between individuals. [7]

CoQ10 from Food

CoQ10 is synthesized in the body, and it is also obtained from the diet. Fish (tuna, salmon, sardines, and mackerel), meat, and vegetable oils are good sources of CoQ10 in food. Meat products are the largest source of CoQ10 in the normal diet.

Cholesterol-lowering Medications and CoQ10

Cholesterol-lowering medications, specifically the so-called “statins”, are effective and safe [9] drugs that reduce the risk of cardiovascular disease events (heart attacks and strokes). However, statin therapy carries risks ranging from muscle pain and weakness to rhabdomyolysis (breakdown of muscle fibers). Myopathy–muscle pain or weakness with blood creatine kinase levels more than ten times the upper limit of the normal range–typically occurs in fewer than one in 10,000 patients on standard statin doses. However, this risk varies between statins, and increases with use of higher doses and interacting drugs. Rhabdomyolysis is rarer; however, with the release of myoglobin into the circulation, it carries a risk of kidney failure. The etiology behind the muscle pain and discomfort in those taking statins is unclear.

A very small double-blind study of 32 patients published in 2007 has suggested that CoQ10 supplementation may relieve the muscle pain associated with starting statin therapy. However, another study, also published in 2007 and randomizing 44 patients, did not find any improvement in muscle pain and discomfort with CoQ10 supplementation, despite the fact that the patients in this study took a higher dosage of CoQ10 than those in the earlier research.

Adverse Reactions

Some individuals have reported diarrhea, nausea, suppressed appetite, heart burn, and abdominal discomfort. There have not been any meaningful studies on pregnant or breast-feeding women.

Simultaneous use of this supplement with warfarin could result in a decrease in the anticoagulant effect of warfarin.

Oral supplementation of CoQ10 increases plasma, lipoprotein, and blood vessel levels, but it is unclear whether tissue CoQ10 levels are increased, especially in healthy individuals.

Summary

Some studies have suggested that cholesterol-lowering medications–the so-called statins–can reduce the synthesis of CoQ10, resulting in decreased plasma concentration [13]. Other studies have not confirmed these findings [14]. Many patients ask whether we have enough convincing and reliable reasons for using CoQ10 for the treatment or prevention of potential statin-related muscle pain. I have to say “No.” Convincing and reliable data is very scarce–almost non-existent. However, I must mention that, if taking this supplement can help a patient who is at risk for more serious heart and vascular complications to remain on statins, a trial of three to four weeks at a dose of 200 mg daily may be worthwhile. Otherwise, longer-term treatment with CoQ10 to treat statin-induced muscle pain or weakness cannot be recommended at this time.

Reference

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hdl- high density lipoprotein

HDL: All You Should Know

hdl- high density lipoprotein

Courtesy: atvb.ahajournals.org

High-density lipoprotein or HDL is one of the cholesterol carriers in our bodies. It builds up around 20 to 30% of total cholesterol. Lipoproteins are water-soluble and have been described as protein-like particles that transfer fat-soluble fatty acids and cholesterol within the body. The main protein piece of HDL structure is apolipoprotein A-1 (apo A-1), which is produced in the liver and intestines.

Four Main Classes of Lipoproteins

High Density Lipoproteins (HDL): These lipoproteins contain 33% cholesterol, 2% of triglycerides, and apolipoproteins A, C, and E.

Low Density Lipoproteins (LDL): These are the primary carriers of cholesterol and are derived from VLDL. These contain 42% cholesterol, 8% triglycerides, and apolipoprotein B100.

Very Low Density Lipoproteins (VLDL): These are produced in the liver to transfer triglycerides. This lipoprotein contains 62% triglycerides, 12% cholesterol, and apolipoprotein B100, E, and CII.

Chylomicrons: These contain the highest amount of triglycerides (90%), compared with all other lipoproteins, and carry fat from the gastrointestinal system to the muscles and fatty tissue. This lipoprotein contains also 3% cholesterol and apolipoprotein B, CII, and E.

The Definition of Low HDL-Cholesterol Level

Adult Treatment Panel III (ATP III) has set HDL levels below 40 mg/dl as the low level; this level is the same for women and men. According to statistics, more men than women have lower levels of these lipoproteins. Based on research data, individuals with higher HDL blood level above 50 mg/dl have a lower rate of heart disease.

Low HDL a Risk Factor for Heart Disease

Multiple studies have shown that low levels of HDL cholesterol is linked to increased risk of heart disease and death; on the contrary, high HDL cholesterol has been associated with lower rate of cardiovascular events. Further studies have also confirmed that a 1% decrease in HDL cholesterol level can result in a 2% increase in heart disease rate.

The Benefits of HDL

One of the most appreciated HDL functions is its ability to extract excess cholesterol from periphery and macrophages and haul it to the liver—so-called reversed cholesterol transport. This lipoprotein has also an anti-oxidative activity and is able to attenuate LDL (low-density lipoprotein). It also has been suggested that HDL may have some anti-inflammatory properties.

It has been further suggested that HDL may have anti-inflammatory and anti-oxidative properties; they reduce the chances of blood clots and improve/maintain the vascular (endothelial) function.

Very Low HDL-C Levels

Two genetic abnormalities could result in low blood level of these lipoproteins.

Familial HDL Deficiency: This is an autosomal dominant disorder and associated with early heart disease but without major systemic findings.

Tangier’s Disease: This is a rare, autosomal co-dominant disorder leading to deposition of so-called foam cells (fatty deposits) in vast areas of the body; this disorder could result in early heart disease, enlarged and fatty liver, enlarged spleen, peripheral nerve damage, and enlarged, orange-colored tonsils.

Causes of Low HDL Cholesterol

  • Physical inactivity
  • Cigarette smoking
  • High carbohydrate intakes (>60 percent of total energy intake)
  • Type 2 diabetes
  • Medications (beta-blockers, anabolic steroids, progesterone)
  • Family history
  • Low HDL-C has been also associated with obesity

In general, in half of the population with low HDL, the cause of this abnormality is due to family history and genes and the other half due to acquired reasons as mentioned above.

Do You Know Your Blood HDL-C Level?

You should find out more and know your lipid profile as accurately as possible. I will discuss the management of low HDL in an upcoming article.

Summary

High-density lipoprotein (HDL) is a major cholesterol carrier in our bodies. These carriers transfer excess cholesterol from periphery to the liver. Studies have confirmed that high levels of these lipoproteins could reduce the chance of heart disease; vice versa, a low level of HDL could result in a higher risk of heart disease.

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Hypertension and medications

Hypertension: Caused by 10 Most Commonly Used Medications

Hypertension is the major risk factor for heart disease. Roughly every 34 seconds, one American has a heart-related event, and approximately every minute, an American will die of one. Below are 10 most commonly used medications that could result in hypertension and blood pressure fluctuations.

Albuterol (e.g. Ventolin, Proair)

Albuterol is a so-called rescue inhaler and used to prevent and treat wheezing, shortness of breath, coughing, and chest tightness caused by asthma and chronic obstructive pulmonary disease (COPD). It works as a bronchodilator resulting in the widening of airways.

Estrogen hormone

Estrogens are a group of chemically similar steroid hormones. Many common medications such as birth control, hormone replacement therapies (HRT), cancer drugs, and others contain synthetic estrogens. Long-term exposure to these hormones can also increase the risks of breast, endometrial, and vaginal cancers in women (US Department of Health and Human Services 2002).

Venlafaxine (e.g. Effexor)

This medication is one of the commonly prescribed drugs for depression and anxiety disorders. It belongs to a class of medicines called serotonin and norepinephrine reuptake inhibitors (SNRIs). The FDA has recommended caution when taking venlafaxine together with migraine drugs such as triptan. This combination can cause a so-called serotonin syndrome resulting in coma and high body temperature.

Decongestants (e.g. Afrin, Sudafed)

These medications work by narrowing the nasal vessels and consequently improving the swelling. Some of these drugs such as pseudoephedrine are combined with other products to produce methamphetamine (“Meth”) one of the most destructive and illegal street drugs. Most commonly available over the counter medications are oxymetazoline  (Afrin) and phenylephrine (Sudafed PE).

ADHD medications (e.g. Ritalin, Adderall)

Most of the medications for treatment of ADHD belong to this class of stimulants and are dopamine reuptake inhibitors (increasing the availability of dopamine in the brain). Some diet pills are made of stimulants.

Migraine Medications (e.g Maxalt)

These medications are used to treat more than 30 million Americans who suffer from migraines. Most of these drugs belong to prescription medicine in a class of medicines called triptans. Triptans are serotonin receptor agonist and control migraine headaches by constricting blood vessels in the brain and relieving the swelling. The most commonly prescribed triptans are Zolmitriptan, Zoming, Sumatriptan (Imitrex) and (rizatriptan) Maxalt.

Corticosteroids (e.g. prednisone)

Corticosteroids could result in significant fluid and sodium retention causing increased blood pressure. There are steroids with higher mineralo-corticoid activity (affecting the adrenal gland) such as hydrocortisone and cortisone and lower mineralo-corticoid activity .

Erythropoietin

This medication is used in patients with chronic kidney disease who are predisposed  to anemia. Erythropoietin could also increase blood pressure in patients with normal blood pressure and in hypertensive patients.

Non-steroidal anti-inflammatory agents (e.g. aspirin, indomethacin, ibuprofen)

Studies have suggested that  non-steroidal anti-inflammatory drugs (NSAIDs) could increase mean arterial pressure by approximately 5.0 mm Hg. These medications could also reduce the effectiveness of blood pressure medications such as diuretics and beta blockers. NSAIDs could also result in kidney failure and fluid retention that could cause a worsening of blood pressure.

Acetaminophen (Tylenol)

Acetaminophen can also influence prostaglandin hemostasis causing high blood pressure. Prostaglandins usually help with dilating the vessels and reducing sodium re-absorption that could improve blood pressure and logically inhibiting prostaglandin will have the opposite effect on blood pressure.   It has been shown that 1 g acetaminophen taken 4 times daily was associated with a 4–mm Hg increase in supine and standing systolic blood pressures.

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Could Statins Cause Diabetes?

Statins and Glucose Levels

Diabetes and Statins

Many readers probably have heard the reports about the recent study, which suggested that there is a higher risk of diabetes when taking statins. This data from Women’s Health Initiative (WHI) hints that the risk of new onset diabetes is higher than suggested by previous studies. The investigators have reported a 48% increased risk of diabetes among the postmenopausal women aged 50-79 years old who take the lipid-lowering medications.

A meta-analysis published in the Lancet in 2010 also showed that statin therapy was associated with a 9% increased risk of diabetes.

A significantly increased risk of diabetes was observed in White, Hispanic, and Asian women. Among African-Americans, who made up 8.3% of the population studied, there was an insignificant 18% increased diabetes risk associated with statin use at baseline.

Should We Stop Prescribing Statins?

What are the important points that we should learn after reading these studies? Is there any reason of changing our approach to treating high cholesterol with this group of medications?

Before concluding or thinking about any changes in our view to statins we should realize the following points,

First that statins are one of the most important groups of medications in the history of medicine. In multiple well designed studies, it has been clearly shown that statins have the ability reducing cardiovascular events in a significant way. We know also that heart disease is the number one killer in our society year after year.

Second that the higher risk for high glucose level and diabetes has been seen in older patients and mostly dosage related. It means those patients who have been on more intensive dosage had higher chance of getting diabetes than others on lower dosage.

But at the same time, the same patients on intensive and higher dosage of statins were better protected against heart disease compared to others on lower dosage.

Third of all we should know that patients on statins are mostly higher risk patients. This is an important issue because we do not know retrospectively how many of these patients would end up with high glucose level or diabetes anyways, if they were not on this medication.

Benefits of Statins Outweigh Diabetes Risks

I am thankful for these kinds of studies because it confirms that nothing in our life can function in an extreme way. In my position, as a Lipidologist, I have seen increased unrefined usage of statins without considering the risk factors of a patient or recognizing the interactions between this group and other medications of the patients in countless cases.  The notion that statins can be put in the public water so everybody is able to enjoy its benefits should be questioned. We as human beings have learned to use automobiles despite its many adverse effects and problems. Using medication in the right and measured way is also not very different. In my opinion, the risks and benefits of the treatment for each patient should be thoroughly examined and the complexity of high cholesterol management should be appreciated. This continuous challenge of finding the right balance between risks and benefit with the purpose of delivering the highest value to our patients make our job as a physician rewarding and in the same time unique.

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