Should I get back on Statins?

Next week, I need to make a decision that may strongly impact my health a decade or two down the road.   The million dollar question, "should I get back on statins?" given that a high fat diet worked for me in the past but is a bit slow to lower my risk factor this time around.  This is a long post so for the short summary, you can skip to the end (Section 4).

1. Background - 1996 to 2012

a. Experts were saying that a high fat diet would not result in weight loss, but would raise cholesterol

A short digression will explain how I got to this point.  In 1996, I started the Atkins diet to combat my growing bulge.  At the time, I was warned not to do it because (1) Eating lots of fat can't make you lose weight; and (2) My cholesterol would rise and I would certainly dye of a heart attack.  My doctor also cautioned me about these issues; but, being an open-minded and intelligent individual, he suggested that my cholesterol be monitored periodically.  He also informed me that the best medical advice of the day was that the ratio of total cholesterol to HDL, called the risk factor, should be below 5 -- but the lower the better.

b. The experts were wrong.  My weight plummeted and my health improved while I was eating lots of fat

A couple months after I started the diet, the ratio tested at almost 8 (see green points on the plot to the right) -- so huge that I was truly concerned.  My cholesterol from a year before was inching up to 5, so 8 was a huge increase.  Since my weight was literally dropping exponentially, as you can see from the red points in the diagram to the right, I decided to wait another 3 months (Atkins stated that the cholesterol in his patients dropped in the long term).  The reading was 6 and then three months later, 4, and six months after that down to almost 3.  So, the critics were wrong.  My weight and cholesterol remained low for over 6 years.  As an added benefit, I felt great; my skin cleared to the sheen of a baby's butt, my weekly migraines disappeared, indigestion was gone, blood pressure plummeted, insomnia was cured, and I was full of energy.  I may be confusing correlation with causation; but, all these effects correlated with my weight loss and risk factor decrease.  The bottom line is that getting over 75% of my calories from fat and about 20% from protein did not make me unhealthy according to the metrics used by the medical profession.

c. The diet was tasty and easy to maintain for more than 6 years

The diet was not difficult to maintain because the food was tasty and enjoyable, and I never felt hungry.  What killed my "healthy" lifestyle was traveling overseas.  In Europe, the "healthy foods" and "exercise" did me in.  My wife and I spent a large fraction of one delightful summer in Belgium.  We had no car so we biked or walked everywhere; yet, I gained over 10 pounds.  A few more years of traveling overseas and my weight and cholesterol slowly crept up; so, I eventually took statins and decided that my health was protected, so I went back to eating pasta, bread, fruit, vegetables, and of course meat.  By the time we got back from our trip to Italy last summer, I was nearing my peak weight of 1996, so I decided to once again go on the Atkins diet for good.

2. The present - Summer of 2012 to Now

I started the Atkins diet for the second time at the end of the summer of 2012.  The data appears to the left (the black points represent my weight).  Over the first two weeks of the diet, my weight hovered between 205 and 210.  Back in 1996, I had lost about 10 pounds in the same time interval (for comparison, blue curve from my 1996 data superimposed in the recent data.)

Internet searches revealed articles that claimed statins were responsible for all kinds of evils, from fog brain to fatigue to increased blood sugar to muscle pain.  I had experienced all these same symptoms to varying degrees.  However, these articles did not offer proof.  They were based on lots of anecdotal evidence.  It is not unreasonable for people to experience all these symptoms as they age, and since statins are prescribed to older people, one could easily confuse correlation with causation.

a. Is Ezetimibe/Simvastatin the Culprit?

I was taking Ezetimibe/Simvastatin for my cholesterol, and it did a good job of lowering it to an acceptable level.  Just as I was getting frustrated with my lack of success on my diet, I also read articles suggesting that while Ezetimibe/Simvastatin does indeed reduce cholesterol, some studies showed that this particular combination (ezetimibe is a cholesterol absorption inhibitor and simvastatin a statin that inhibits HMG-CoA) was no better in outcome than a simple statin.  And since statins alone did not lower my cholesterol, I wondered whether I was really being protected from heart disease.

b. Testing the hypothesis that Ezetimibe/Simvastatin interferes with weight loss

While I could not determine the efficacy of the Ezetimibe/Simvastatinin in protecting me from heart disease, I could test its effect on weight loss.  On day 19, I stopped taking my medication and the weight began to consistently drop.  I accept that this may have been a coincidence, but I noticed improvements in my overall well-being - again a subjective observation.

I regularly play floor hockey year round and ice hockey in the winter.  Since starting my Ezetimibe/Simvastatinin prescription, I felt a general degeneration of physical stamina.  After sprinting for 10 seconds, I was exhausted, and needed to rest for longer and longer periods of time between shifts. More depressing was the unpleasant exhaustion I experienced for at least 12 hours after playing.  The nature of my fatigue was not the good feeling after a workout.  It was a diseased feeling.  Hard to explain, but I attributed it to getting older.  Remember, correlation does not imply causation, so I had no reason to believe that Ezetimibe/Simvastatinin was to blame.

About two years after starting to take my medication, I had an unexpected hit of fog brain.  It was very distressing and it resulted in a lasting general fuzziness of my senses.  I was concerned enough to visit my doctor, who did various tests including an MRI of my head.  Nothing showed up.  Again, I attributed this to aging.

After I stopped taking Ezetimibe/Simvastatinin this year, my energy and stamina returned.  I can now sprint in multiple bursts in a shift without fatigue and I once again feel blissful fatigue after each game, which fades after just a couple hours.  The improvements are so extreme that I am certain that the effect is real. And its been this way consistently for five months.  It's harder to say whether or not the termination of medication has impacted my occasional bouts of fog brain. On this front, I would say the results are inconclusive.

c.  Effects of high fat diet on cholesterol

In my diet of 1996, my cholesterol drop lagged my weight loss by about 6 months.  In reading many books on the topic, and even mentioned in Atkins book from the early 70s, the first phase of an Atkins diets is associated with a cholesterol increase due to cholesterol entering the blood stream as fat is metabolized.  Once weight loss levels off, cholesterol drops.  This is indeed what I observed, with more than a factor of 2 drop in my risk factor.

To track my results this time around, I am monitoring my blood (glucose, ketones, triglycerides, HDL, LDL, etc.) on a weekly basis.  My experiment is complicated by the fact that I stopped taking medication during the diet and then only later started doing blood tests.  In the newer figure above, the horizontal dashed red line represents my risk factor (total cholesterol/HDL) when on medication and the red points show my measurements after getting off the meds.  There is a clear increase in risk factor over time, though with sawtooth features.  The horizontal solid red line is the danger level, and I am in very high territory, though not as high as during the initial phase of my 1996 diet.

Because I have changed both my diet and my medications, there is no clear way to deconvolute the two.  However, there is one striking feature;  my weight plateaued between about day 40 and 90, followed by a precipitous increase in the rate of weight loss.  In contrast, the 1996 data shows a steep and steady drop.    Could the plateau be due to my metabolism making an adjustment to me stopping the medication, and I am finally in the state of rapid fat loss, thus the increase in risk factor?  Did the medication change the equilibrium point of my metabolism to a more unfavorable level? Or am I just becoming old?

d. Cholesterol is not the whole story - the size of LDL particles

New research has shown that LDL comes in a distribution of sizes.  The tiny particles are the ones that lodge themselves in the arteries, while the big fluffy ones do no damage.  Sadly, there is no such test available in my area.  However, studies show that the triglyceride/HDL ratio is a proxy for the LDL particle size and levels below 2 are good.  The green squares show my data and the horizontal green line labels a ratio of 2.  In this regard, my numbers during my 2012 are good.

3. The Science

The issue of diet has been highly politicized and much of the research is not science.  I recommend that readers check out the books by Gary Taubs to understand how our society has become so averse to fat even in the face of contrary evidence. There have been many criticisms of his book that he selectively chooses data that supports his views and ignores the other data. To some extent this is true.  However, his explanations ring true based on my experiences.  The problem is that counter arguments also make sense, so how is the patient to decide the best course of action?
 
My intention is to study the scientific literature to develop an understanding of the ideal healthy lifestyle.  Sadly, this is a daunting task given the huge number of studies.  Also, given the complexity of the human body, variations between individuals, and the difficulty in doing clean studies, it is likely that no single strategy exists that applies to all individuals.  If this is the case, it is foolish to come up with a one-size fits all recommendation, yet that is how patients are treated.

a. How can we judge the truth of the matter?

 Here are the facts.

1. Double blind studies are the hallmark of research that involves people but are not are clearly not possible to implement in diet research.  My own study is not blind at all, and therefore not reliable as a test of any hypothesis, though it does confirm that increasing fat intake and decreasing carbohydrates has resulted in weight loss (1996 data and 2012 data), and based on the 1996 diet, cholesterol drops too.  So, high fat diets can do some good, but are there downsides?
2. Epidemiological Observational Studies (EOS) observe diets of large populations in search of correlations between diet and health (this can include whole countries or studies such as the huge one of doctors and nurses who periodically respond to questionnaires). These can be used to generate hypotheses but do not constitute proof of causation.  Other studies are needed to prove anything.  Unfortunately, such studies are often deemed to constitute proof.  EOS studies have good statistics but do not prove anything.
3. Controlled studies, in which individuals are fed strict diets under researcher supervision, or are taught to independently continue with the diet with frequent monitoring are the best comprise.  The degree of intervention required necessarily limits such studies to smaller groups of individuals and therefore have sparser statistics.
4. Studies on one individual, such as mine, give lots of data but suffer from bias and lack of statistics. This approach gives indicators that can be used by the individual to make medical decisions.  It is satisfying when an N=1 experiment correlates with larger studies.  Indeed, my weight loss dats from 1996 is much cleaner than the data in the literature analyzing the Atkins diet.

There are certain statements that can be definitively tested even in small studies.  For example, the statement that people can't loose weight on low carb diets is falsified by evidence to the contrary.  Controlled studies show that some people loose lots of weight on this diet.  Similarly, eating lots of fat does not guarantee that you will have high cholesterol.  We must also acknowledge that there are populations that eat high carbohydrate diets who are healthy, so it would be false to state that such diets always lead to poor health.  However, this observation does not prove that carbohydrates make you healthy.  The problem always comes down to generalizations.  I need to make a decision about me, and what happens in the case of the average population is of no help.

4 What should I do?

Here is the sequence of events:

A. Historically, when I went on low fat diets (including a vegetarian diet), I

1. never lost weight
2. was always hungry
3. suffered from idigestion
4. couldn't sleep
5. had chronic migraines
6. felt miserable

B. On a high fat diet,

1. I lost weight dramatically
2. My cholesterol risk factor dropped by more than a factor of 2
3. The diet was tasty, I ate as much as I wanted and was never hungry
4. Many of my other indicators of health got better
5. I felt great

 C. I slowly drifted off of the high fat diet due to

1. overseas travel were it was impossible to get enough fatty foods
2. pressure to conform when dining out
3. constant bombardment by the media and the medical establishment of the evils of fat
4. slowly losing faith in the wisdom of staying on a low fat diet given all the persistent voices to the contrary

D. After abandoning the diet

1. I tried to stay away from processed carbohydrates and eat less fatty meats
2. my weight drifted upwards
3. my cholesterol got high enough to require a prescription
4. I was prescribed Lipator(R) but it did not lower my cholesterol
5. Vytorin(R) 10/12 dramatically lowered my cholesterol
6. while on Vytorin(R) for 5 years

• I became extremely fatigued after exercise
• my blood pressure increased
• I developed fog brain
• my weight increased to almost its 1996 peak

E. After going back on the diet

1. My weight loss was stalled until I stopped taking Vytorin(R)
2. My weight is now dropping fast
3. My cholesterol levels started rising after going off the Vytorin(R)
4. My fatigue after exercise is gone
5. My doctor is urging me back onto statin

So, should I go back on statins?  I am seeing my doctor on the 12/17/12, and will then have a blood test.  I want to develop talking points with him to bring up the pertinent questions and I also want to have a decision tree ready before we talk so that I can make choices without emotion.

Here is what I am thinking:

1. I do not do well when eating carbs, so my only alternative is to eat lots of fat.  Since I need to continue eating fat, I need to better understand if it is having a negative affect on my health based of my higher cholesterol and C-reactive protein numbers during my recent diet. My CRP was up a few months ago, but still below the recommended value.
   
2. If statins decrease my cholesterol and my C responsive protein (two purported risk factors for heart disease - though a causal link is not definitively established), then I would gladly take statins if they cause no other ill effects.
3. Statins alone did not lower my cholesterol but the combination drug did.  However, it has been shown that the outcomes (i.e. disease or death) for the combination drug is no better than for statins alone.  So will a statin really help me if it does not decrease my cholesterol or CRP?
4. Given that the combination drug reduces my ability to exercise, and may have other side effects, I prefer to avoid them.
5. Given that statins have been shown to have positive outcomes, perhaps acting as anti-inflammatory agents, then maybe I should take them even if they do not lower cholesterol and then check my CRP and decide later if I should quit.
6. What if there are other systemic effects of statins?  Will they interfere with my insulin response and unravel my positive response to the high-fat diet?  Could this lead to an increased chance of diabetes? Given my data, the combination drug seemed to have had an adverse effect.  Are plain statins better?
7. Sometimes no action is better than action if the benefits are not well defined and the risks unknown. If statins will not help with my chances of decreasing heart disease risk, perhaps I should not take them given the potential risks.
8. Large scale drug tests do not take into account individual variability.  What in my medical history can be used to make a more informed decision?

 My plans for now are to go ahead with a blood test next week.  If my numbers are getting better, I'll probably hold out for another 3 months then plan another visit to my physician.  This is the simplest outcome given the fact that I expect a 6 month lag between starting the diet and stabilization of my cholesterol levels.  The complication is that the combination drug may have delayed this effect.  If  my lipid panel is the same or getting worse, should I stay the course to give my diet a chance, or should I take the statins and risk them making me worse off in the long run by interfering with my diet?

There are clearly no clear-cut answers. What do you think?

Eating lots of fat to lose weight

Classifying foods into the broad categories of healthy and unhealthy misses important nuances. Disease is associated with bacteria, viruses and prions, so foods that are properly cleaned are not unhealthy in the sense of causing disease. It is true that eating only a single food item exclusive of others would deprive the body of vitamins, but if it is not a poison that causes direct harm to the body, it is not unhealthy.

Some people swear by their convictions that organic foods are healthier than foods produced on large corporate farms. Even as a young adult, I was puzzled over the concept of organic foods. In 10th grade chemistry class, we learned that organic molecules are by definition ones that contain carbon atoms, which are covalently bonded to each other and to other atoms. Aren't all foods organic? Petroleum is organic, but it would certainly make one sick if ingested. Some of the most potent toxins are organic.




As I learned later in life, "Organic" is a trademark that describes how foods are cultivated. Manure may be used instead of the chemicals found on larger commercial farms, and fruits and vegetables are harvested later so that they ripen naturally rather than in cardboard crates. If people are willing to pay a higher price for a particular farming practice, so be it.

Conservatives may turn to Fox News for their daily dose of self deception, while liberals may enjoy shopping in hippie-like co-ops to fortify their beliefs in the spiritual purity associated with ingesting so-called healthy foods. In the end, scientifically reliable sources and the preponderance of evidence should rule the day.

Several years ago, I spent part of an evening at a ski lodge watching a program on an investigative TV news magazine. An independent laboratory did a chemical analysis of fruits and vegetables grown on large corporate farms and found no trace of the chemical fertilizers and pesticides used to enhance yield. Ironically, the "organic" foods were found to have high levels of bacteria that cause intestinal diseases. When confronted by these facts, the spokesman for the organic farmers stated very confidently that "when washed properly, 'organic' foods were at least as healthy as foods grown on non-organic farms." He is right in the sense that "at least" also includes "is equal to." In other words, if you wash your organic lettuce very carefully, it will be equivalent in safety to the lettuce sold by large and evil corporations.

The food pyramid suggests that a diet should be high in grains and low in fat. Fruits and vegetables are good and meat in large quantities is bad. One would assume that the food pyramid, introduced by the U.S. Department of Agriculture, is based on solid science; but, it is not.

Many years ago, my wife introduced me to the low carbohydrate Atkins Diet. Being the mid 1990s, there was far less information available on the internet than today; but, I had access to databases of scientific journals. What few studies were available in medical journals at the time did not seem to indicate any adverse effects of such a diet. In contrast, all of the people around me thought me crazy to consider eating lots of fat to lose weight. "That diet sounds mighty dangerous," they would opine. A common criticism of low carbohydrate diets is repeated on many web sites. Consider the following:

Dr. David E. Norwood writes [sic] in an article about the dangers of the Atkins diet. Because of the severe restriction of carbohydrates, a person will lack fiber, which can cause gastrointestinal problems like constipation. Also, the high protein diet is high in cholesterol and saturated fat. This can lead to heart disease, kidney damage and possibly some cancers, Dr. Norwood warns. Because you are depleting the body’s primary source of energy, carbohydrates, the person will feel fatigued and incur a loss of energy. The Atkins diet also does not promote learning about portion control or serving sizes, so the person does not develop any healthy eating habits.

Again, the use of "healthy" in reference to eating habits...

Shortly after I started the Atkins Diet, I visited my physician for a baseline blood test. He warned me that such a diet was not a good idea, but agreed to order blood tests every couple of months. After two weeks on the diet, I had lost 6.5 pounds from a starting weight of 213.5 pounds. My friends were warning me that this was just a loss in water weight. However, I was starting to feel better then ever. My chronic insomnia, which goes back as far as I can remember, disappeared as did my weekly migraine headaches. My chronic heartburn also subsided. Oddly, I felt more energetic and less hungry throughout the day. By day 161, I was down to 174 pounds. At a height of 6'1" I was becoming concerned that my weight was dropping too quickly - about 0.25 pounds per day; so, I started to increase my carbohydrate intake and my weight stabilized, then began to increase a tad.

The only change in my life at that time was my diet. My exercise regimen remained constant as did my stress on the job and my satisfaction with family life, etc. Of course, my story up to this point is a worthless testimonial without hard data. When I started the diet, my physician informed me that the best indicator of risk factor was the ratio of bad cholesterol to good cholesterol, so I used that as a metric.

Above and to the right is a plot of my weight (red points) and the risk factor (green points) over the first six years of my diet. I used an electronic bathroom scale that is accurate to 0.1 pound and took my weight every morning at the same time within about a 30 minute variation.

The smooth blue curve is a plot of a model that is a sum of two exponentials. An exponential function usually is a good model of the time dependence of a process that is the result of a single rate, in this case my weight drop. However, because I changed to a diet with higher carbohydrate content about 3 months later, this introduces a second rate - thus a sum of the two exponentials. The purpose of the model is solely to provide a rough mathematical estimate of the data, which happens to reproduce its shape pretty well.

My diet was heavily skewed in favor of fat. Breakfast consisted of eggs with lots of cheese, and sometimes bacon on the side or pieces of salami mixed in with the eggs for a little extra flavor. Lunch consisted of a small amount of green salad with lots of meat and cheese and a mayonaise-based dressing with no carbohydrates. Dinner was steak, chicken, or a burger smothered in cheese but no buns; my diet was heavily skewed towards red meat. Later in my diet, I added string beans as a side dish. When having lunch with my children at McDonald's, I would order 4 double cheeseburgers minus the bus. At Pizza hut, I would eat a whole pizza without the dough (served on the metal pan), with extra cheese, of course. I even ordered doughless pizza in Korea, were it took a conference of all the employees to determine if it was possible.

During the diet, I took mega vitamins to make sure that I was not missing the essentials.

My experiment was designed to test the two hypotheses originally proposed by Atkins: low carbohydrate diets lead to weight loss and lowered cholesterol. The plot of the data clearly shows my weight loss, which I kept off for almost a decade. Throughout this time, my cholesterol risk factor oscillated in a good range of 3 to 5 (correlated with my carb intake).

In the long run, the diet was difficult to maintain not because it was unpleasant to me, but because of protests from my wife (she loves culinary variety); and, the difficulty of finding low carbohydrate dishes at restaurants or as dinner guests of our friends. I first strayed from the diet by casual cheating at such outings. Interestingly, my largest weight gain started in the summer of 2o05 while in Belgium, where our only form of transportation was walking and biking. Furthermore, we ate "healthy" European foods that included wonderful bread, fruits and vegetables. My weight increased, as did my cholesterol.

I totally gave up on the diet from that point on because it was impossible to maintain in my travels; and, it was difficult to maintain due to social pressures. I was thought weird and inconsiderate for having such a strange diet. It would be wonderful if one could get a low carb meal with the same kind of respectful deference as is given to vegetarians.

My sample-of-one-subject experiment is not necessarily representative of the general population. However, having a Sheldonesque obsessive compulsive personality, my experiment was probably better controlled than is possible in a large population. During the time period shown in the plot, I carefully nionitored my carb intake, slowly adding carbs as my weight stabilized at my target value.

Later, scientifically controlled studies found the same result, as is described below. Note how my data is very similar to the low carb plot, and how the weight loss is faster and cholesterol control better in the low carb diet compared with the low calorie diet that is typically considered healthy.

Below is a verbatim summary of the article, "Weight Loss with a Low-Carbohydrate, Mediterranean, or Low-Fat Diet," which appeared in The New England Journal of Medicine 2008; 359:229-241, July 17, 2008.


Methods

In this 2-year trial, we randomly assigned 322 moderately obese subjects (mean age, 52 years; mean body-mass index [the weight in kilograms divided by the square of the height in meters], 31; male sex, 86%) to one of three diets: low-fat, restricted-calorie; Mediterranean, restricted-calorie; or low-carbohydrate, non–restricted-calorie.

Results

The rate of adherence to a study diet was 95.4% at 1 year and 84.6% at 2 years. The Mediterranean-diet group consumed the largest amounts of dietary fiber and had the highest ratio of monounsaturated to saturated fat (P<0.05 p="0.01)." style="font-weight: bold;">Conclusions

Mediterranean and low-carbohydrate diets may be effective alternatives to low-fat diets. The more favorable effects on lipids (with the low-carbohydrate diet) and on glycemic control (with the Mediterranean diet) suggest that personal preferences and metabolic considerations might inform individualized tailoring of dietary interventions. (ClinicalTrials.gov number, NCT00160108.)

Given the evidence, I am greatly annoyed that people still consider fat unhealthy. There are no documented adverse affects of a high fat diet when carbs are removed. It is mostly hearsay and pontification of supposed experts. I am once again trying to stick with a low carb regimen. Perhaps it is futile, but I have already lost 5 pounds in less than two weeks. The real test of my resolve will be the short trip we are taking to the west side. I hope that I will still be eating "healthy" when we return.