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Thursday, July 25, 2013

Nobel Prize and recognition denied due to early death from ovarian cancer

Google doodle honors birthday of biophysicist Rosalind Franklin

British X-ray crystallographer made great strides in our understanding of the molecular makeup of DNA and RNA but missed out on Nobel Prize.
Google doodle honoring Rosalind Franklin.
(Credit: Google)
Google devoted its doodle on Thursday to mark the 93rd birthday of Rosalind Franklin, a British biophysicist and X-ray crystallographer who made great strides in our understanding of the molecular makeup of DNA and RNA but missed out on the Nobel Prize.
British biophysicist Rosalind Franklin.
(Credit: Jewish Chronicle Archive/Heritage-Images)
Born in London on July 25, 1920, Franklin showed exceptional scholastic aptitude at an early age. After studying chemistry at Cambridge, Franklin went to work as a research associate at King's College London in the Medical Research Council's Biophysics Unit. During her tenure at King's College, she captured X-ray diffraction images of DNA that led to the discovery of the DNA's double helix. Her data was the basis for a 1953 hypothesis regarding the structure of DNA that led to the 1962 Nobel Prize.
Franklin died of ovarian cancer in 1958 at age 37 and was ineligible for Nobel Prize nomination in 1962. The honor was bestowed on Francis Crick, James Watson, and Maurice Wilkins based on their work contributing to the understanding of nucleic acids and not exclusively for their DNA structure discoveries. However, Crick wrote in 1961 that Franklin's data was "the data we actually used" to formulate their hypothesis on the structure of DNA.
While her exposure to X-ray radiation is sometimes linked to the illness that killed her, other members of her family have died of cancer.
Franklin's studies also contributed to the understanding of the molecular structures of viruses, coal, and graphite.
Google's doodle represents Franklin gazing at the double helix structure of DNA with an image of the X-ray diffraction image of DNA (known as Photo 51) at the end.

Saturday, July 6, 2013

New Medical Office in Murrells Inlet. Dr. JP Saleeby now accepting New Patients

Accepting patients.

For more information on General Preventive Care. Full service General Practice in the Myrtle Beach area. If you were seen by Dr. Saleeby at another center and have labs, x-rays pending for review. If you are a bHRT patient needing follow up, please call the toll free number to schedule an appointment.www.PriorityHealthSC.com

Office location 637-C Bellamy Ave, Murrells Inlet, SC. Call to arrange appointments now
800-965-8482.


General Practice and Preventive Integrative Medicinewww.PriorityHealthSC.com

Saturday, June 1, 2013

Oolong Tea story

One night long ago mother moon  beheld a beautiful scarlet comet burning in the sky where before had been only darkness. It seemed to her the most wondrous thing she had ever seen.
“Who are you?” she cried.
“I am Hong Long, the red dragon. I have traveled far and am weary but yet I have far to go, for indeed my journey never ends.”
Mother moon felt great pity for the handsome stranger and her heart opened to him. “Hong Long,” she said, “Why not stay with me for a while? I am lonely and you are tired. Let us comfort each other”
“Alas, I cannot linger for it is my fate to wander.” Said Hong Long, “But while I am in your sky I would be happy to have your company.”
And so it happened that for many weeks Mother Moon and the comet kept each either company. Hong Long told her stories of his travels and the wonders he had seen. Mother Moon shared her love of mankind, whom she watched over every night, and long did they laugh at the silly things people did as they rushed through their fleeting lives. In time, as is natural, Mother Moon and Hong Long fell in love.
But far too soon Hong Long had passed through Mother Moon’s sky and was on the far side of the night. Mother Moon confessed her love to Hong Long and he admitted he felt the same. “Must you really leave?” pleaded Mother Moon.
“I truly wish I could stay.” Said Hong Long, “But I am as God made me. I must continue my journey or I die.”
“Either way I would lose you,” sighed Mother Moon, “So, choose life and go your way.” As she spoke these words Hong Long passed from her sky and she saw him no more.
In sorrow, Mother Moon turned her attention to the Earth down below. As she glanced down a single white tear fell from her eye.  Below a tea bush was opening her leaves to feel the night breeze. Mother Moon’s tear fell directly on her. The tea bush was suffused with simultaneous feelings of love and unbearable sadness.
Ever since then the tea from that bush and her children has had a unique silky sweet essence that man in his ignorance called “milk” for he had no other word to describe this sensation. But we know it is really tears of longing that fell from the moon.
So goes the story of how milk oolong (called on our site Golden Lily Oolong) came to be.
 
Ralph Kenney - Owner & Founder
The Immortalitea Company
The Immortalitea Company, 965 Wilson Blvd., Unit1121, El Dorado Hills, CA 95762, USA

Monday, May 27, 2013

www.saleeby.net web portal is launched with new face

Check out the new face of www.saleeby.net it is the new updated version of the Saleeby web portal. Bill Sever my webmaster redesigned and incorporated the old ''Flash" version opening page into a secondary link and created a new Front Page that illustrates more of what Dr. Saleeby is doing these days and associated health and wellness links. Check it our and leave a comment. A special prize to anyone who can find the hidden "typo" within the contents of the first page.

Tuesday, May 21, 2013

US vs Chinese Doctor Burnout Study

Chinese vs US Docs: Comparing Burnout and Lifestyle

Carol Peckham
May 15, 2013

Comparing Chinese and US Physicians on Lifestyle and Burnout

In an interesting collaboration, Medscape shared the questions in its 2013 lifestyle and burnout survey with DXY (www.dxy.cn), which is China's largest online academic portal for physicians and life-science professionals. DXY was established in 2000 and currently has over 3 million registered members and average daily page views of 1.8 million. In this comparison, Medscape and DXY sought to identify differences in how US and Chinese physicians perceive their lifestyles and their experience of burnout.
The first interesting observation to emerge was the large proportion of younger physicians who responded to the DXY survey. Only about 6% of the approximately 6000 Chinese respondents were over age 45. This higher rate of younger physicians is the result of major expansion in Chinese college/university enrollment since 1998, producing dramatic growth in the number of certified Chinese physicians over the past decade. In order to make a reasonable comparison with the Medscape survey results, then, only US physician respondents younger than age 45 were included in the analysis, which totaled about 7500.
There was also a challenge in comparing specialties; a third of the respondents to the DXY survey reported that they were involved in Chinese traditional medicine or a mix with standard medicine. Another 24.1% said that they were internists. The assumption was that these groups taken together would be considered primary care, for a total of 57%. On the US side, a quarter of the respondents reported being family physicians (12%) or general internists (13%). The remainder practiced in subspecialty areas. There was also a slight difference in the proportion of men and women: 32% of Chinese respondents were women compared with 41% of US respondents.

Burnout and Its Causes

Major differences exist between the 2 physician populations in their responses to the questions about burnout. Both groups were given the same definition: "Do you suffer from burnout, defined as loss of enthusiasm for work, feelings of cynicism, and a low sense of personal accomplishment?" Of those who responded, 82% of Chinese physicians said that they were burned out compared with 42% of US physicians.

Burnout Severity

In regard to the severity of burnout, it was difficult to compare the responses because the questions were phrased differently. US physicians were asked to rate their burnout on a scale of 1 to 7, where 1 = "it does not interfere with my life" and 7 = "it is so severe that I am thinking of leaving medicine altogether." Their responses, with a mean of 3.65, were as follows:
 1 (6%)
 2 (19%)
 3 (24%)
 4 (21%)
 5 (17%)
 6 (7%)
 7 (5%)
Chinese respondents were given 4 options to choose from:
 It is manageable and I'm not making any changes (36%)
 It is manageable but I need to make some changes in hours/workload/etc. (52.2%)
 I am thinking of leaving my current position (7.3%)
 I am thinking of leaving medicine altogether (4.5%)
We somewhat arbitrarily matched up the answer options:
US options 1 and 2 = Chinese option 1
US options 3-5 = Chinese option 2
US option 6 = Chinese option 3
US option 7 = Chinese option 4
We then created a table that offered a rough comparison (Table 1). The percentages indicate that although burnout rate is extremely high in China, few Chinese (and US, for that matter) physicians are planning on making any major changes.
Table 1. Severity of Burnout
OptionsChineseUS
It is manageable and I'm not making any changes36%25%
It is manageable but I need to make some changes in hours/workload/etc.52.2%62%
I am thinking of leaving my current position7.3%7%
I am thinking of leaving medicine altogether4.5%5%
 

Causes of Burnout

When asked about the top causes of burnout, again the questions were posed differently, with US physicians asked to rank each stressor on a score of 1 to 7, where 1 = very unimportant and 7 = extremely important. Chinese physicians were given the same options but were asked to choose the top 5 and rank them in order from most to least important. The Chinese survey also excluded 3 options. Therefore, instead of providing numeric values, Table 2 simply lists the most to the least significant stressors for each group, according to the results of each survey. Insufficient income is the number-one stressor for Chinese physicians, and long hours at work are important causes of burnout for both groups.
Table 2. Causes of Burnout for US and Chinese Physicians, Ranked Most to Least Important
United StatesChina
Too many bureaucratic tasks*Income not high enough
Spending too many hours at workSpending too many hours at work
Income not high enoughLack of professional fulfillment
Feeling like just a cog in the wheel*Too many difficult patients
Too many difficult patientsInability to provide patients with the quality care they need
Lack of professional fulfillmentCompassion fatigue (overexposure to death, violence, and/or loss in patients)
The present and future impact of Affordable Care Act*Difficult colleagues or staff
Inability to provide patients with the quality care that they needDifficult employer
Difficult colleagues or staffIncreasing computerization of practice
Difficult employer 
Increasing computerization of practice 
Compassion fatigue (overexposure to death, violence, and/or loss in patients) 
*These options did not appear in the Chinese survey.

Income Disparities

The difference in income in these 2 populations, as reflected in a question about savings and debt, is significant (Figure 1). Among US physicians, 43% report that they have either minimal or no savings, compared with 87% of Chinese physicians. Only 13% of the latter have adequate savings or more, compared with 51% of US physicians. Chinese physicians make far less than their US counterparts. Reports have given official monthly salary ranges for Chinese physicians of 3500 to 10,000 yuan ($560 to $1600).[1,2] Although Chinese physicians make far more than the average worker, they still make less than other professionals. For example, pharmaceutical sales reps can earn 2 or 3 times more than a physician. As a result, many Chinese physicians supplement their income with industry kickbacks. According to a 2010 Lancet article,[3] in the mid-1980s, when the socialist economy was reformed into a more market-driven system, hospitals lost public funding and physician income declined. To compensate for lost revenue, hospitals and physicians were allowed incentives from industry. The unfortunate consequence was the overprescribing of certain drugs and diagnostic tests and an increase in healthcare costs. For example, 75% of Chinese patients with a common cold are prescribed antibiotics, compared with the international average of 30%. China is currently experimenting with different payment methods for providers along with organizational changes to reform the current system.[3]


Figure 1. Savings and debt.

Patient Relationships

Difficult Patients

Chinese physicians ranked "difficult patients" high on their list of burnout causes. Changes in the healthcare system have caused deterioration in physician-patient relationships over recent decades. The most dramatic example of this is increased violence, including homicide, toward physicians by patients or their families. Negative media coverage and the belief that doctors are corrupted by pharmaceutical kickbacks have played a major role in precipitating these events.[4,5] In a previous survey of Chinese physicians, 66% reported that their hospitals encountered 1 to 3 medical disputes per month. In that survey, 78% blamed the tension between patients and physicians on the lack of government funding to hospitals, and 70% placed the blame on negative reports from the public media.[6] A recent article published in the American Journal of Medical Quality offered guidance on preventing and handling violence in hospitals.[7]

Domestic Status

When asked where they were happiest, 60.6% of Chinese physicians indicated at home, 6% at work, and a third in both places. This question was not asked in the 2013 US survey, but it did appear in the 2012 survey, where 46.1% of US physicians said that they were happiest at home, 4.3% at work, and 49.6% in both places. Both the US and the Chinese 2013 surveys requested physicians to rate their happiness at home on a scale of 1 (very unhappy) to 7 (very happy). Although the majority of Chinese physicians preferred home to work, they scored their happiness at home as only 3.4, compared with 5.5 for US physicians. Chinese physicians' mean satisfaction score at work was only slightly lower (3.3) and it was much lower than that of their US counterparts (4.8).
Chinese physicians are more likely to live alone than their US peers (27% vs 16%), which might contribute to their lower satisfaction with home life (Figure 2). They also have far fewer children (Figure 3), a rate that is not limited to this profession, given China's 32-year 1-child-only policy. (There are indications that this policy may be changing.[8])


Figure 2. Domestic status.


Figure 3. Number of children.

Vacations, Volunteering, and Religiosity

Vacations

Regarding the kinds of vacations that physicians take, although the options were the same for both groups, the questions were posed differently, with US physicians able to choose as many as they wanted and Chinese physicians asked to rank their favorites. Still, it's possible to compare their preferences (Table 3) and to assume that Chinese and US physicians, with some slight differences, share the same interests.
Table 3. Vacations, Ranked From Most to Least Favorite
United StatesChina
Spending time with familySpending time with family
Exercise/Physical activityTravel
TravelExercise/Physical activity
ReadingReading
Cultural events (eg, movies, theater, museums)Cultural events (eg, movies, theater, museums)
Food and wineSurfing the Web
Surfing the WebFood and wine
Musical activities (instrumental, vocal)Engaging in social media (eg, discussion boards, Facebook, Twitter)
GardeningMusical activities (instrumental, vocal)
Visual arts (eg, photography, painting, sculpture)Visual arts (eg, photography, painting, sculpture)
Engaging in social media (eg, discussion boards, Facebook, Twitter)Managing finances/investments
Managing finances/investmentsGardening
GolfWriting (nonmedical)
Hunting or fishingCollecting
CollectingHunting or fishing
Writing (nonmedical)Golf
 
In looking at the amount of vacation that each population takes, however, Chinese physicians fare far worse, with 64% getting less than 1 week each year, compared with 5% of US physicians (Figure 4).


Figure 4. Amount of vacation taken by US vs Chinese physicians.

Volunteering and Religiosity

Volunteer rates are high among both US and Chinese physicians, with only 27% of US and 32% of Chinese physicians reporting that they don't volunteer at all. The type of volunteer work they do, however, differs in many ways (Figure 5). Chinese physicians are most likely to choose work that is related to their profession -- clinical work (31%) and tutoring (12%) -- rather than to personal interests. Work with religious organizations is popular among US physicians (22%) but basically nonexistent among Chinese physicians. This is not surprising considering their response to the survey question on religion, where 86.8% said that they did not have a religious or spiritual belief and 12% said that they did but did not practice. In comparison, three quarters of US physicians claimed a belief and 60% attended services.


Figure 5. Types of volunteer activities.

Health and Fitness

Chinese physicians exercise far less than their US counterparts (Figure 6), which could be explained at least partly by answers on some questions that indicate how little time they have for personal activities. On causes of burnout, "too many hours at work" is ranked the number 2 stressor, and to the question about vacation, only 12% of Chinese physicians responded that they are able to take more than 2 weeks off. One can surmise that if they work all the time and take little time off, exercise is an activity that gets sacrificed.


Figure 6. How often Chinese and US physicians exercise.
Still, Chinese physicians' responses to questions on physical well-being and health were mixed. For instance, they have a lower rate of overweight (26%) or obesity (0%) compared with US physicians (31% and 6%, respectively). They also have a higher rate of underweight than their US peers (14% vs 2%), but it is not possible to know whether this indicates a healthy diet or health problems (Figure 7).


Figure 7. US and Chinese physicians' BMIs.
Chinese physicians tend to smoke a bit more than US physicians, although their rate of having never smoked is still very high (85% vs the US rate of 90%) (Figure 8).


Figure 8. History of smoking.
Chinese physicians drink much less than their US peers (Figure 9): 54% do not drink at all, compared with a third of US physicians. Also, 55% have fewer than 1 drink per day, compared with 41% of their US counterparts.


Figure 9. History of alcohol use.

Summary

A substantial percentage of both Chinese and US physicians report burnout. The problem is worse in China, however, where income levels are low and much more time is spent at work. Physician exercise levels and vacation time are very reduced in China compared with the United States, although alcohol use is low and there is less overweight and no obesity. In addition, Chinese doctors face deteriorating respect from patients and even violence directed against them, a result of higher medical costs, a negative media, and an association with pharmaceutical industry kickbacks. Various efforts are now being made in China to improve the situation, including reforming drug company reimbursement practices and undertaking experimental programs to increase income and improve care.

References

  1. Denoble D. Are China's doctors about to get a major bump? November 6, 2012. Asia Healthcare Blog.http://www.asiahealthcareblog.com/2012/11/06/are-chinas-doctors-about-to-get-a-major-salary-bump/ Accessed May 7, 2013.
  2. McGregor T. China's doctors worthy of higher pay. July 25, 2011. CRJ English.http://english.cri.cn/6909/2011/07/25/2743s650260.htm Accessed May 7, 2013.
  3. Yip WC, Hsiao W, Meng Q, Chen W, Sun X. Realignment of incentives for health-care providers in China. Lancet. 2010;375:1120-1130. Abstract
  4. [No authors listed]. Chinese doctors are under threat. Lancet. 2010;376:657. doi: 10.1016/S0140-6736(10)61315-3.http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2961315-3/fulltext Accessed May 7, 2013.
  5. Yu D, Li T. Doctor stabbed to death two days after warning in The Lancet. Lancet. 2011;377:639. doi: 10.1016/S0140-6736(11)60231-6.
  6. Yu D, Li T. Facing up to the threat in China. Lancet. 2010;376:1823-1824. doi: 10.1016/S0140-6736(10)62161-7.http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2962161-7/fulltext Accessed May 7, 2013.
  7. Feng Z, Li T. Guideline for preventing violence at hospitals in China (2011-2012). Am J Med Qual. 2013;28:169-171. doi: 10.1177/1062860612453194. Epub 2012 Aug 13.
  8. Alcorn T. China's new leaders cut off one-child policy at the root. 2013. Lancet. 381;983. doi:10.1016/S0140-6736(13)60697-2. http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2813%2960697-2/fulltext?rss=yesAccessed May 7, 2013.
 

Monday, May 13, 2013

If cherries are good, grapes are even better for a CHF patient.


Grapes activate genes that reduce high blood pressure related heart failure

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It has been known that grapes are able to reduce heart failure associated with chronic high blood pressure. A US study appearing in the "Journal of Nutritional Biochemistry" has now shown how this effect is achieved: The grapes activate a number of genes that improve the levels of glutathione, the most abundant cellular antioxidant in the heart.
The scientists from the University of Michigan hypertensive, fed heart failure-prone rats a grape-enriched diet for 18 weeks. The results reproduced earlier findings that grape consumption reduced the occurrence of heart muscle enlargement and fibrosis, and improved the diastolic function of the heart. Furthermore, the mechanism of action was uncovered. Grape intake "turned on" antioxidant defense pathways, increasing the activity of related genes that boost production of glutathione.
In the next phase, which will continue into 2014, E. Mitchell Seymour, the head of the study, aims to further define the mechanisms of grape action, and also look at the impact of whole grape intake compared to individual grape phytonutrients on hypertension-associated heart failure. His hypothesis is that whole grapes will be superior to any individual grape component. "The whole fruit contains hundreds of individual components, which we suspect likely work together to provide a synergistic beneficial effect," reasons Seymour.
Seymore, EM. Diet-relevant phytochemical intake affects the cardiac AhR and nrf2 transcriptome and reduces heart failure in hypertensive rats, The Journal of Nutritional Biochemistry - 25 March 2013 (10.1016/j.jnutbio.2013.01.008)

Tuesday, May 7, 2013

Life IS a bowel of Cherries especially with someone with Gout.


Do Cherries Really Work in Gout?

Jonathan Kay, MD
May 03, 2013
Hello. I am Jonathan Kay, Professor of Medicine and Director of Clinical Research in the Division of Rheumatology at the University of Massachusetts Medical School and UMass Memorial Medical Center, both in Worcester, Massachusetts.
In the 1931 musical Scandals, Ethel Merman sang a song that began, "Life is just a bowl of cherries." It turns out that gout might also be just a bowl of cherries. Gout is a very prevalent condition, affecting more than 8 million individuals in the United States, and is a very common reason for patients to present to the rheumatologist.
Recently, many patients have come in saying that they take cherry extract or eat cherries to prevent an attack of gout. Is there any scientific basis for this?
In December 2012, Zhang and colleagues[1] from Boston University Medical Center published a very interesting paper inArthritis and Rheumatism. In this case/control study, patients with gout were enrolled in an Internet-based registry. Investigators picked a 2-day period just before an attack of gout and compared that period with the 2 preceding days and the 2 subsequent days as control periods unrelated to an attack of gout.
The investigators validated the diagnosis of gout in more than 550 patients by looking at medical records authorized by the patients for review, and found that this group of patients had more than 1250 attacks of gout. The investigators looked at various self-reported dietary items, including cherries and other unrelated foods. They found that the intake of cherries before an attack of gout reduced the likelihood of experiencing an acute attack of gout by one third compared with the intake of unrelated foods.
This interesting finding suggests that there may be some basis to the ingestion of cherry extract or cherries to reduce attacks of gout. What might be the scientific basis for this? Cherry extract blocks the tubular reabsorption of urate and increases urate excretion in the urine. Cherry juice may also block xanthine oxidase and reduce the production of uric acid.
Cherry extract has a synergistic effect with allopurinol. Moreover, cherries contain anthocyanins, which are somewhat anti-inflammatory. Thus, there may actually be a reason why patients are making the right decision by ingesting cherries. Future controlled clinical trials of cherry extract should help to confirm or disprove this very interesting epidemiologic observation.
Thank you very much for your attention, and I look forward to seeing you on Medscape.

References

  1. Zhang Y, Neogi T, Chen C, Chaisson C, Hunter DJ, Choi HK. Cherry consumption and decreased risk of recurrent gout attacks. Arthritis Rheum. 2012;64:4004-4011. Abstract
 

Wednesday, May 1, 2013

Cholesterol and Statins: Part II


Cholesterol & Statins:  Part II

by Yusuf M. Saleeby, MD
to be published in American Fitness magazine (Mar/April 2013 issue)

In the last issue (Cholesteron & Statins : Part I, American Fitness Jan/Feb 2013), the discussion centered on cholesterol, that necessary but often maligned molecule.  The previous article made one realize that this steroid compound is a double edged sword as it relates to health concerns.  While essential for the life of human cells, high serum levels of total cholesterol and in particular elevated non-HDL-cholesterol, designated bad cholesterol, end up being harmful to our cardiovascular system.

Plenteous research, time and money have been devoted to the study of this low density lipoprotein substance that carries cholesterol (LDL-C) out of the liver to cells.  It was discovered that too much would ‘’clog up’’ arteries back in the 1970s.  This was the driving force for aggressive development of medications to combat the formation and lower the level of LDL-C in circulation.1

As previously mentioned in Part I, dietary restriction of cholesterol is of limited value.  When we limit our oral intake of dietary cholesterol, our body produces cholesterol in the liver to compensate for a predetermined genetic set point.  Thus a cholesterol restrictive diet alone is usually not enough to reduce markedly elevated levels of the ‘’bad cholesterol.’’ 2   Dietary restrictions alongside weight loss and exercise are a more effective approach.  Lipid lowering medications like the class of statin drugs have a more potent affect.

History:

Statins or HMG-CoA reductase inhibitors are a class of drug that inhibits an enzyme which plays a central role in manufacturing cholesterol in the liver.  The term ‘’statin’’ is derived by the last few letters of some of the original drugs developed, lovostatin and simvastatin being examples.  Historically, the Japanese biochemist Dr. Akira Endo isolated the first statin drug (mevastatin), but it showed toxicities and never made it to market.  Not long afterwards in the early 1970’s researchers from Merck pharmaceuticals following up on published research and developed the first marketable statin (lovostatin) which was extracted similar to Dr. Endo’s from the fungus (Aspergillus terreus).1,3   Incidentally, there are naturally occurring statins, namely those found in the oyster mushroom (Pleurotus ostreatus) and the extracts from fermented red yeast rice fungi (Monascus purpureus).4    This latter extract is used commercially as a natural alternative to reduce cholesterol.

Merck capitalized on the statin drugs Zocor® and Mevacor®, which earned the company over $1-Billion each by 1995.  Dr. Endo was also the beneficiary of the 2006 Japan Prize and Lasker-DeBakey Clinical Research Award in 2008 for his achievements in the field of lipid chemistry.  Today there are a number of statins in the marketplace, as both stand alone drugs and in combination with other lipid lowering agents.  Names the public would recognize include Lipitor® (atorvastatin), Lescol® (fluvastatin), Mevacor® (lovastatin), Pravachol® (pravastatin), Crestor® (rosuvastatin) and Zocor® (simvastatin).  All are lab synthesized drugs except for lovastatin and pravastatin which are derived directly from naturally occurring yeast and bacterium. 

Statin Drugs (HMG-coA reductase inhibitors)

Numerous medical trials show the statins as having a major affect on lowering LDL-C, and thus bringing the total cholesterol in serum down.   Statins can, with varying degree raise HDL-C levels.  When compared to diet alone, statins are proven more effective in lowering LDL-C.  However, this is not accomplished without some undesirable side effects.  The drugs mostly affect the liver hepatocytes and muscle cells.  The toxicity of natural occurring statins in mushrooms is unobtrusive, but some serious muscle damage can occur with pharmaceuticals.  One such incident occurred when Baycol® (cerivastatin) came to market some years ago.  It was so toxic that the Federal Drug Administration (FDA) had to remove it from pharmacies in 2001.5

Recent changes to the National Institute of Health (NIH) guidelines for testing individuals now suggest that children between the ages of 9 to 11 have lipid screening performed.  Most statins are approved for use in children 10-years and older, but use should be judicious.  Statins are classified as Category X in pregnancy which means they are contraindicated in expectant women because of high risk of birth defects.6 

Statin drugs produce muscle pain in approximately 30-percent of individuals who take them.  Other side effects include liver damage, digestive problems, rash, cataracts, an increase in blood glucose and type-2 diabetes (T2DM) risk, and neurological conditions as a rise in amyotrophic lateral sclerosis (ALS) incidence.  Those that are at higher risks are females, those taking other cholesterol medications, people with small body frames and with underlying kidney or liver disease and/or diabetes.  Being over the age of 65-years also increases risk for untoward effects for statin users.  There are reports of a fifty-percent increase in risk of developing age-related cataracts with those using statin drugs compared with non-users.5,6,7

To combat detrimental side effects, sometimes a prescriber will switching from one statin to another, or reduce the dose, or change the dosing schedule to every other day.  If a person is taking a statin they should avoid grapefruit and grapefruit juice as this can potentiate the drug’s harmful effects.  The cardiac rhythm drug amiodarone (Cardarone®) has an interaction with simvastatin.  Lopid® another lipid lowering agents concomitant use with statins is ill advised.  Some HIV drugs (protease inhibitors) interact with lovastatin in a negative way.  There are even interactions with antibiotics and antifungal drugs.  The immunosuppressant drug cyclosporine (Sandimmune®) can increase risk for rhabdomyolysis (muscle breakdown) as well.5,7   With statin use monitoring of liver function tests (transaminases) and muscle biomarkers creatine kinase (CPK) and aldolase are indicated routinely along with monitoring the effects of the drug to meet goal (serum LDL-C and ApoB levels).  Yet other measures to reduce untoward effects of statin drugs have been to add coenzyme Q10, correct Vitamin D and thyroid deficiencies, or switch to a non-statin regimen.  There is a theoretical risk that lowering cholesterol drastically can affect production and levels of beneficial steroid hormones.  More study in this area is needed to confirm or dispel fears.

Since the mapping of the human genome, genetic tests have been developed to help predict coronary risk and the effectiveness of statin therapy.  The blood test analyzing the KIF6 genotype (offered by Berkeley Heart Labs) may aid doctors in directing lipid therapy as polymorphisms in this gene identify those at higher risk for coronary heart disease.  Once identified, those individuals can reduce their risk with statin therapy.  The SLCO1B1 genotype test, help clinicians predict who may be at greater risk for muscle damage while on lipid lowering therapy.  Carriers of the SLCO1B1 gene are more likely to have problems with statin induced myopathy then those who do not carry that gene.8,9

With the drug market eventually becoming saturated with statin medications and coming under fire with a plethora of side effects, researchers began looking elsewhere.  Focus was centered on manipulation of beneficial lipoproteins, namely HDL-C.  It was reasonable to think that raising HDL-C would scavenge the bad cholesterol away to be recycled and thus not be around to form foam cells.  Research had already proven that reduction in native LDL-C and foam cells, which lead to arterial plaque formation, would lessen the risk for heart disease.  A genetic malady, albeit rare gave promise that developing pro-HDL-C drugs may be a superior alternative to statin therapy.  Tangier Disease afflicts a very small number of people worldwide, but with extremely low levels of HDL-C there is a tendency for more advanced cardiovascular disease in younger victims.10-13   Initial trials of HDL-C raising drugs were a disappointment to those proponents of raising HDL, but research continues in this direction.14 

In all fairness to statin drugs, there have been reports of other benefits such as improving endothelial function, reducing inflammatory C-Reactive Protein, coronary plaque stability and reduction in thrombus formation (clots).  Additionally, for reasons not quite clear there was a reduction in cancer risk while study subjects were on statin drugs.15,16

According to an October 2012 JAMA report on trends in lipids in the United States between 1988 and 2010, total cholesterol and LDL-C numbers experienced a reduction.  Unfortunately during the same time frame triglycerides (TG) went up while HDL-C remained unchanged.  This is all apparently the result of aggressive statin use with Americans having dyslipidemia.17

Pharmaceutical Alternatives to Statin Therapy

Ezetimibe a drug known in the US market as Zetia® is an alternative for those who cannot tolerate statin therapy.  Ezetimibe can lower cholesterol by interrupting intestinal re-absorption of cholesterol.  However, studies have reported continued use can thicken the arterial walls.  So it is recommended as a drug of last resort by some.  Ezetimibe is also used in conjunction with statins in some dual agent drugs such as Vytorin®.  Dual therapy is a means of using two agents at lower individual doses to achieve a particular lipid level goal and limit side effects.18,19

Fibric Acid derivatives such as gemfibrozil (Lopid®) and fenofibrate (TriCor®) are other alternatives to statin therapy.  While not as effective in lowering LDL-C as stains, they do raise HDL-C and lower Triglycerides (TG).  Fibric Acid drugs are known to improving insulin resistance as an added benefit.  However, in combination with statins they can increase risk for liver and muscle injury.20,21

Vitamin B3 (nicotinic acid) in high doses is commonly used to raise HDL-C.  This naturally occurring substance while relatively safe in high doses does come with the undesirable side effect of flushing.  Flushing can be thwarted by a delayed release delivery system (Niaspan®) by prescription and by premedication with low dose aspirin.22

Questran® and WelChol® are in a class of drug called bile acid resins.  Bile acid resins are used to lower LDL-C and total Cholesterol by sequestration and expulsion in feces.  They are effective and are another pharmaceutical alternative with limited systemic effects used in statin-intolerant patients.22

Cholesteryl ester transfer protein (CETP) inhibitors came on the scene recently.  They were touted as the new wonder drug for cholesterol management, or so it was thought.  This class of medication is used to raise HDL-C.12,13   However, initial attempts by Roche pharmaceuticals were halted in phase III trials due to failure of the agent (torcetrapid) to perform safely.14  Nonetheless, the Academy for the Advancement of HDL Science is optimistic about future developments and new drugs in the pipeline.15

Natural Alternatives to Statin Therapy

Fish oil is a clinically proven agent in lowering cholesterol and triglycerides.  The omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are well researched as being effective for dyslipidemia.  Krill oil is a newer arrival into the forum; it has been peddled as being better than fish oil by proponents.  Having a lower DHA and EPA content than fish oil and costing 5 to 10-times as much, it may not be a preferred choice.  Only a few high concentrated Krill or Krill/Fish oil combinations give you the necessary concentrations of DHA/EPA to lower lipids and provide cardiac risk reduction.23   Fish oil has the FDA nod of approval for lowering cholesterol and triglycerides (TG) and even comes as the FDA approved prescriptive Lovaza®.  While Lovaza® is rather expensive; those seeking pharmaceutical grade fish oil have many less expensive choices that are equally effective and safe.  Caution should be taken when using fish oil with other blood thinning medications prior to elective surgery or with those with seafood allergies.

Besides fish oil there are several herbal and dietary supplements that can lower cholesterol and heart disease risk.  Garlic in some studies reported a reduction of total cholesterol by a few points.  Caution however, must be taken when taken in conjunction with blood thinners such as Coumadin® as bleeding risks may increase.24   Oat bran and barley have been studied and demonstrate that with regular ingestion a person can lower cholesterol and cardiac risk.25  

The resin Guggulipid derived from the mukul myrrh tree, illustrates a reduction of LDL-C and total cholesterol in clinical studies performed in India.  Demonstrating Guggulipid to be an important natural lipid lowering agent will require more scientific examination.  As mentioned earlier the extract of fermented red yeast rice is a naturally occurring statin.  While showing lower risk of toxicity, there is a linear correlation with lower effectiveness due to its reduced potency.  The product of the waxy coating of sugar cane and beet skins known as policosanol was shown in several clinical trials to lower LDL-C when taken orally in standard doses.24,26,27

Extracts of fenugreek, artichoke, yarrow, and holy basil may also help lower cholesterol, but again clinical trials will have to prove this to the medical community.  The use of ginger, turmeric, and rosemary in cholesterol lowering preparations are common as there may be some benefit.  Consumption of dietary fiber, soy based foods, and plant sterols (aka phytosterols, compounds similar to cholesterol) can reduce LDL-C.  Phytosterols interfere with the re-absorption of cholesterol and can be found in commercial bread spreads like Benecol®, Promise®, and Smart Balance®.26,27   With the advent of ‘’Medical Foods” there are patented combination therapies, sanctioned by the FDA for prescriptive use, that have shown promise in scientific studies.  Metagenic’s UltraMeal360® is an example of such a prescriptive medical food.28   Another medical food is Hypertensa® designed for those with metabolic syndrome by Physician Therapeutics; and more of these safer alternatives are on the horizon.29

Whether you put your chips on lowering LDL-C or raising HDL-C one important fact remains; both courses of action will reduce cardiovascular risk, but when you add weight loss and exercise then risk of heart disease really drops.  According to Mayo Clinic reports, weight loss of between 5 and 10 lbs can lower LDL-C levels.  For every six pounds of weight loss you can increase HDL-C by 1mg/dL in serum levels.  Physical activity, as in sustained exercise, lasting 30 minutes or more at least five times a week can yield a five-percent increase in HDL-C.  Smoke cessation is also a big player; quit smoking and you can increase your HDL-C by ten-percent and in a year reduce your heart disease risk by fifty-percent.26,27,30,31

Controlling cholesterol is a complicated process for physicians and patients alike.  Wrought with drug tolerance, unproven alternatives, and cost issues, it is a daunting task to manage dyslipidemia.  Along with ever changing practice guidelines for serum cholesterol levels offered up every couple of years by national medical societies and institutions, therapeutic recommendations will likely remain in flux for the unforeseeable future.


References:

1.      Endo A., The discovery and development of HMG-CoA reductase inhibitors, J. Lipid Res. 1992;33 (11): 1569–82. 

2.      Ahmed SM, Clasen ME, Donnelly JE. Management of dyslipidemia in adults. Am Fam Physician, 1998;1;57(9):2192-2204, 2207-8.

3.      Simons, John. "The $10 billion pill", Fortune magazine, January 20, 2003.

4.      Liu J, Zhang J, Shi Y, Grimsgaard S, Alraek T, Fønnebø V, Chinese red yeast rice (Monascus purpureus) for primary hyperlipidemia: a meta-analysis of randomized controlled trials". Chin Med 2006;1: 4.

5.      Golomb BA, Evans MA., Statin Adverse Effects: A Review of the Literature and Evidence for a Mitochondrial Mechanism. Am J Cardiovasc Drugs 2008;8(6): 373–418. 

6.      Prescriber’s Letter, January 2012 (vol. 19, no. 1) and June 2012 (vol. 19, no. 6) section on Statins and Dyslipidemia.

7.      Statin Side Effects, Retrieved from http://www.mayoclinic.com/health/statin-side-effects/MY00205 (Accessed 12/3/2012)

8.      SLCO1B1 Genotype testing, Retrieved from http://www.bhlinc.com/clinicians/test-descriptions/SLCO1B1-Genotype-Test (Accessed 12/3/2012)

9.      KIF6 Genotype testing, Retrieved from http://www.bhlinc.com/clinicians/test-descriptions/KIF6, (Accessed 12/3/2012)

10.  Grover SA, et al., Evaluating the incremental benefits of raising high-density lipoprotein cholesterol levels during lipid therapy after adjustment for the reductions in other blood lipid levels. Arch. Internal Med. 2009;169:1775.

11.  Singh IM, et al., High-density lipoprotein as a therapeutic target: A systematic review. JAMA. 2007;298:786.

12.  High Cholesterol: Cholesterol-lowering medication, Retrieved from http://www.webmd.com/cholesterol-management/guide/cholesterol-lowering-medication, (Accessed 12/3/2012)

13.  HDL Cholesterol: How to boost your ‘good’ cholesterol, Retrieved from http://www.mayoclinic.com/health/hdl-cholesterol, (Accessed 12/3/2012)

14.  "Roche provides update on Phase III study of dalcetrapib." Roche press release, May 7, 2012.

15.  Academy for the Advancement of HDL Science, Retrieved from http://lipid.org (Accessed 12/3/2012)

16.  Ridker PM, Danielson E, Fonseca FAH et al., Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. NEJM 2008;359 (21): 2195–207.

17.  Mitka M., Cholesterol drug controversy continues. JAMA 2008;299 (19): 2266.

18.  Carroll, MD., et al, Trends in Lipids and Lipoproteins in US Adults, 1988-2010., JAMA, 2012;308(15):1545-1554.

19.  Garcia-Calvo M, Lisnock J, Bull HG, Hawes BE, Burnett DA, Braun MP, et al. The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1). Proc Natl Acad Sci, 2005;102(23):8132-7.

20.  Jun M, Foote C, Lv J, et al., Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis. Lancet 2010;375 (9729): 1875–1884.

21.  Steiner G., Atherosclerosis in type 2 diabetes: a role for fibrate therapy?. Diab Vasc Dis Res, 2007;4 (4): 368–74.

22.  Alternative Treatments for High Cholesterol, Retrieved from http://www.webmd.com/cholesterol-management/guide/high_cholesterol_alternative-therapies, (Accessed 12/3/2012)

23.  Krill Oil: A substitute for Fish oil? Prescriber’s Letter August 2010, Retrieved from http://prescribersletter.therapeuticresearch.com (Accessed 12/3/2012)

24.  Cholesterol-lowering supplements: Lower your numbers without prescription medication, Retrieved from

http://www.mayoclinic.com/health/cholesterol-lowering-supplements/CL00013 (Accessed 12/3/2012)

25.  Jenkins, D. [Oats bran and Barley on Cholesterol] American Journal of Clinical Nutrition, 2005; vol 81:pp 380-87.

26.  Alternative Cholesterol Treatments, Retrieved from http://naturaldatabase.therapeuticresearch.com (Accessed 12/3/2012)

27.  Alternative Cholesterol Treatments, Retrieved from Cleveland Clinic Department of Nutrition and Cleveland Clinic Heart Center web sites (Accessed 12/3/2012)

28.  Metagenics UltraMeal360®, Retrieved from http://www.metagenics.com/products/health-conditions/hypercholesterolemia, (Accessed 11/16/2012)

29.  Hypertensa® Package Insert, Retrieved from http://tmedpharma.com/docs/monographs-5-22/Hypertensa_Product_Monograph_for_website_5-22-08.pdf (Accessed 11/16/2012)

30.  Smith SC Jr, Benjamin EJ, Bonow RO, et al., AHA/ACCF secondary prevention and risk reduction therapy for patients with coronary and other atherosclerotic vascular disease: 2011 update: a guideline from the American Heart Association and American College of Cardiology Foundation endorsed by the World Heart Federation and the Preventive Cardiovascular Nurses Association. J Am Coll Cardiol. 2011;58(23):2432-2446.

31.  Greenland P, Alpert JS, Beller GA, et al., 2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2010;122(25):e584-e636.


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Yusuf (JP) Saleeby, MD is medical director of WellnessOne and WellnessFirst which offer extensive and advanced cardiovascular and stroke biomarker and genetic analysis, including lipid subtypes, Lp(a), CRP, HDL2 and HDL3, LDL1-4, ApoB, NT-proBNP, Lp-PLA2, and the 4q25, 9p21, ApoE, KIF6 and SLCO1B1-Genotype tests.  He is a regular contributor to American Fitness and serves on the medical advisory board.  He can be reached for comment at ymsaleeby@gmail.com.

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