Wednesday, April 14, 2021

An Addition to the Cardiac Alphabet: “a” Novel Risk Factor

 

Lipoprotein (a) or Lp(a), pronounced “El Pee Little a”, is a lipid particle that is associated with plaque in the heart arteries, heart attack and cardiac death. What is Lp(a), what is its link to heart disease and how is it treated?

 

Lp(a) was discovered in 1963, but has been largely forgotten since then due to the lack of good treatment options.  Newer medications have shown some efficacy in lowering Lp(a) sparking a resurgence in research.  Plaque or blockage in the heart arteries mostly consists of low density lipoprotein (LDL, the “bad” cholesterol). In fact, plaque is more than 90% LDL cholesterol. Lp(a) however is also needed initiate and propagate plaque formation in the heart arteries. In addition, Lp(a) promotes blood clotting and inflammation, two properties contributing to heart disease. Abnormal elevation in Lp(a) is a common genetic entity. Lp(a) elevation above 50 mg/dl affects one in five people in the US or approximately 60 million Americans. Studies have linked Lp(a) to a higher risk for heart attack, stroke, aortic stenosis (thickening and blockage of  the aortic valve, limiting blood flow from the heart), heart failure, kidney disease and heart deaths.

 

Who should be tested for an abnormal Lp(a) level? Lp(a) may be measured in the blood and levels over 50 mg/dl are abnormal. However, the risk for heart disease increases as Lp(a) levels increase. Therefore, slight elevations may not be as clinically relevant as high levels of Lp(a).  There are a couple of scenarios where measuring Lp(a) may be beneficial. One consideration is in a patient with a strong family history for coronary artery disease (first degree relative with heart disease at age 60 or younger). Another possibility is a patient who has had recurrent heart events (heart attack or repeated cardiac stents) despite adequate treatment with a statin. In these cases knowing that there is an elevated Lp(a) level may change therapy. 

 

How should elevated Lp(a) be treated?  Ideally a medication should be chosen that reduces both LDL and Lp(a). Statins are the treatment of choice for patients with heart disease and high LDL levels. Statins lower LDL and reduce the risk for heart attack and cardiac death. Unfortunately, statins do not reduce Lp(a) levels. In fact, statins can increase Lp(a) by 10% to 20%.  Niacin reduces Lp(a) levels by 15-25%. Unfortunately, niacin has not been shown to reduce the risk for cardiac outcomes and has significant side effects (flushing of the skin after ingestion). For these reasons, niacin has not been used for heart patients for some time. PCSK9 inhibitors are new monoclonal antibodies that have very good data in heart disease. PCSK9 agents reduce LDL nearly 50% on their own and by 60% when used with a statin.  They have been shown to reduce the risk for heart attack and cardiac death. They are injected under the skin every two weeks and, since they are not a statin, do not have muscle pain as a side effect. In addition, PCSK9 agents reduce Lp(a) levels by 25%.  Another new medication is currently undergoing trials. Inclisiran reduces LDL by 50% and Lp(a) by 20%. It is also given by injection and is administered twice yearly. 

 

While the data associating Lp(a) with a higher risk for heart artery plaque, heart attack and cardiac death is well established, it is not known whether lowering Lp(a) will improve cardiac outcomes.  This is important because many treatments in cardiology that initially seemed promising (examples include vitamin E, hormone replacement therapy and folic acid) did not reduce the risk for heart attack or cardiac death when tested in large scale clinical trials and have thus fallen out of favor.  Trials are currently underway testing the Lp(a) hypothesis of heart artery disease and cardiac outcomes and the answer should be available very soon. Until then, we should try to identify patients who have significant elevations in Lp(a) and treat them as best we can. 


Tuesday, March 23, 2021

Q: Crazy Conspiracy Theory or Useful Supplement?


Over the past several months, the news has been reporting about a shadowy figure named “Q”, who has promulgated many baseless and false theories over a wide range of subjects, mostly about politicians and elections. Similarly, the body has a shadowy “Q”, coenzyme Q, which is ubiquitous and is involved in multiple metabolic pathways. Since the election is over, we will tackle questions about the body’s Q.

 

Coenzyme Q10 (CoQ10) is a naturally occurring substance produced by the body. It plays an essential role in generating energy for the cell. CoQ10 is found in abundance in tissues with high-energy requirements, such as the heart or skeletal muscle. CoQ10 is made in all tissues of the body and the pathway that produces it also produces cholesterol. In general, the body produces as much CoQ10 as it needs, but with aging, the levels of CoQ10 can diminish. Also, importantly, statin use can decrease CoQ10 levels.  CoQ10 is also available as a nutritional supplement with a global market estimated at $600 million. The supplement has been studied extensively and is safe with mild adverse reactions such as dizziness, insomnia, nausea and diarrhea. CoQ10 supplementation may play a role in statin associated muscle pain and in congestive heart failure.

 

Statin associated muscle problems can occur in 10 to 20% of patients who take statins to lower cholesterol. It is one of the major reasons why patients stop taking statins.  Symptoms range from minor muscle aches, to severe muscle pain, cramps and weakness, to muscle breakdown and toxicity (called rhabdomyolysis, a serious condition that can lead to hospitalization, kidney failure and even death).  Unfortunately, there is no objective test to determine statin associated muscle pain. A lab test, creatine kinase or CPK, can be elevated if there is muscle damage, but the test isn’t always reliable. The diagnosis is made by clinical symptoms and stopping the statin (if symptoms improve, they may have been due to the statin). No one knows the cause of statin associated muscle pain, but it has been hypothesized that depletion of CoQ10 may play a role. As such, many trials have been conducted to see if supplementation with CoQ10 would be beneficial. Unfortunately, the trials have been inconclusive and contradictory; some trials show that CoQ10 is beneficial while others do not.  One trial reported more muscle pain in patients who took a statin plus CoQ10 compared to statin plus placebo; a finding known as the nocebo effect. Even though benefit is questionable, there is no harm in taking CoQ10 supplements. Therefore, there may be a role. For patients with statin associated muscle pain the following may be an approach:

1)  Stop the statin for 1 or 2 months

2)  If symptoms improve, restart the same statin at a lower dose or try a different statin 

(if symptoms don’t improve, the muscle pains may be due to something else)

3)  If symptoms return at a low dose or on a different statin, a trial of CoQ10 may be used at a dose of 200 to 400 mg per day

 

Congestive heart failure (CHF) occurs when the heart weakens and cannot pump blood effectively. Fluid builds up in the lungs (causing shortness of breath) or throughout the body (causing swelling in the legs and abdomen).  CHF is the number one cause for hospitalization in the US. CoQ10 is involved with the production of energy in cells, especially heart cells. If CoQ10 is depleted, the heart cells will have reduced energy leading to the weakening of the pumping function of the heart. It has been shown that there are reduced levels of CoQ10 in the blood and in the heart tissue of CHF patients. It has been theorized that supplementation of CoQ10 might improve CHF.  Studies have shown that CoQ10 supplementation does improve symptoms, reduces hospitalizations and decreases cardiac death in chronic CHF patients.  It may also improve the ejection fraction (a measure of the heart’s pumping function). It must be noted that these studies are preliminary and that CoQ10 should only be used in the context of a clinical trial, and not for routine use as yet.

 

CoQ10 is emerging from the shadows and being extensively studied in heart disease.  Depletion of CoQ10 may play a role in statin associated muscle pain and in congestive heart failure.  While awaiting definitive data from future research, nutritional supplementation with CoQ10 may be beneficial in these conditions. It must be noted that CoQ10 is not approved for any medical condition by the Food and Drug Administration (FDA).  In addition, routine us of CoQ10 is not needed in cardiac patients as the body manufactures the amount of CoQ10 that it requires.

 

 

 

Monday, February 15, 2021

Can You Teach An Old Drug New Tricks?

 


It's a warm summer evening in ancient Athens. Archimedes is sitting in the agora and notices redness, swelling and pain in his big toe after drinking a kylix of wine. He goes to the market and is given an herb by a local farmer. After taking the herb, his big toe starts to feel better. He runs through the streets crying "Eureka!".

 

Colchicine is an anti-inflammatory medication which is used to treat acute episodes of gout. It is derived from the plant Colchicum autumnaleor autumn crocus. It was in fact used in ancient Greece, but as a laxative. The ancient Egyptians used it to treat rheumatism.  Colchicum plant extracts were used to treat gout starting about 550 AD. Benjamin Franklin, who suffered from gout, is credited with bringing Colchicum plants to the United States when he returned from Paris after completing his duties as French ambassador. Colchicine was first extracted in 1821 by French chemists and soon thereafter became a popular remedy for gout. It was approved for use in the US by the FDA in 1961. The anti-inflammatory effect of colchicine is very different from nonsteroidal anti-inflammatory (NSAID) medications and aspirin.  For more than 50 years colchicine was used exclusively to treat gout. Over the past ten years it’s anti-inflammatory properties were found to be useful in heart disease. Even more recently, it has been used in COVID-19. So colchicine, an old drug, finds itself at the intersection of inflammation, heart disease and COVID-19. Here are some clinical scenarios where colchicine has found new uses.

 

Pericarditis is inflammation of the sac lining the heart (the pericardium).  The most common cause of pericarditis is a virus, and symptoms are usually preceded by an upper respiratory infection, the flu or, recently, COVID-19.  Chest pain is the main presenting symptom, often associated with changes on the EKG or fluid around the heart on echocardiogram. Acute episodes of pericarditis are treated with anti-inflammatory agents such as aspirin, NSAIDs, colchicine or steroids.  Colchicine has been used since 1987 to treat acute pericarditis and recently it has been shown that colchicine combined with either an NSAID or aspirin was better for treatment than aspirin or NSAID alone.  With the combination, symptoms usually resolve within 72 hours, but treatment should continue for three months to prevent repeat episodes. About 15 to 30% of patients will have recurrent episodes of pericarditis. As with acute bouts, colchicine plus either aspirin or an NSAID successfully treats recurrent pericarditis. 

 

Coronary artery disease (CAD) or plaque in a heart artery can lead to a heart attack or chronic angina (chest pain). Low-grade inflammation within the walls of the heart arteries leads to plaque build up and blockage. Inflammation can also cause acute rupture of a plaque causing a heart attack. Previous research showed that a strong intravenous anti-inflammatory agent (a monoclonal antibody) improved outcomes for CAD patients but was expensive and had significant side effects. Would cheap, easily available colchicine be beneficial? Colchicine has been shown to reduce inflammation within the walls of arteries, so theoretically it should be helpful. Several studies examined the use of colchicine in chronic stable CAD patients and patients who had a recent heart attack. These studies show that colchicine consistently reduces the risk for cardiovascular outcomes (especially repeat heart stents).  Therefore, it seems that colchicine can be added to the cardiac medication armamentarium.

 

COVID-19 is another inflammatory disease. In severe COVID-19, the immune system’s inflammatory response overtakes the body affecting the lungs, heart, and blood vessels especially hard.  High dose, intravenous steroids are used to combat the inflammatory consequences of the disease.  Given colchicine’s anti-inflammatory properties, can it be used to prevent serious complications in outpatients with mild COVID-19? Several trials are underway to answer the question, one of which was recently reported. The trial enrolled 4000 patients with a diagnosis of COVID-19 within the previous 24 hours. In addition, one high-risk characteristic was needed (older age, obesity, diabetes, hypertension or underlying heart or lung disease).  Colchicine reduced hospitalizations, the need for a respirator and deaths. However, the trial was not peer-reviewed and with the sting of hydroxychloroquine fresh in mind, the data are being interpreted with caution. It is felt that colchicine may be beneficial, but that there is still insufficient evidence to use the medication.  Fortunately, other trials are ongoing and may be able to provide yet another use for colchicine.

 

Currently, a massive amount of research is being conducted focusing on inflammation, it’s effects on the body and novel agents to treat it. Meanwhile, the tried and true drug colchicine, with known efficacy, few side effects, wide availability and low cost, may be an answer to treat inflammatory diseases both old and new.

 

Sunday, January 24, 2021

Red Meat, Red Flag?


The holidays are over. The gifts have been unwrapped. The decorations are down. The holiday ham has been cooked and eaten. Now that it’s a new year, it’s time to examine whether that ham is healthy or not.

 

For years, a cornerstone of teaching in medical school, and in cardiology training programs, is that red meat is bad for health.  Red meat is animal muscle and is defined as any meat that is a dark red color before it is cooked. It has been extensively studied for many years and has consistently been associated with higher risks for heart disease, cancer, diabetes and death. However, it is important to distinguish between unprocessed and processed red meat. Unprocessed red meat is defined as beef, pork, veal or lamb. Processed red meat is preserved in some way, by smoking, salting or curing. Examples of processed red meat include sausage, delicatessen meat (such as salami or ham or pepperoni), hot dogs and bacon.  Both types have similar amounts of cholesterol and saturated fat. Processed meat has slightly more calories and less protein per serving than unprocessed meat. The big differences between the two are the salt content and the preservatives. Processed meat has four times the amount of salt and many more preservatives than unprocessed meat.  So eating a sandwich with low fat deli meat may be less healthy than eating a juicy hamburger! Based on these differences, dietary guidelines have recommended low consumption of unprocessed red meat and avoidance of processed red meat. 

 

Then the tide changed in October 2019 when the Annals of Internal Medicine published a series of papers on red meat. They also published, and aggressively promoted, guidelines based on the findings.  These guidelines were contrary to the current dogma and stated that it was fine for Americans to continue their current consumption of both processed and unprocessed red meat. They stated, “No need to reduce red or processed meat consumption for good health”. This set off a media frenzy with headlines touting “It’s OK to eat red meat!”.  What the papers actually found was that the studies were of low quality and that the researchers could not say for certain that eating red meat was bad for health. One of the problems was that studies compared a red meat diet to other unhealthy diets (which were high in refined starches, sugars and saturated fats). Compared to these other unhealthy diets, consumption of red meat did not look as bad. Critics pointed this out as well as other numerous flaws in the data. In addition, it came to light that the authors did not disclose funding from the beef industry, which could have biased the results. The Annals then published a correction. 

 

So, is it OK to eat red meat? It certainly makes sense that red met increases the risk for heart disease. Red meat is associated with increased levels of LDL cholesterol (the “bad” cholesterol). Red meat is also high in iron, which has been show to increase the risk for heart attack and heart deaths. The high salt content of processed meats increases blood pressure and damages blood vessels. Lastly, preservatives such as nitrates are associated with heart artery disease. What if red meat was compared to a diet based on plant based proteins (such as nuts, peas, beans, or lentils)?  This study was performed and published in December 2020. Researchers followed 40,000 American men for 30 years and compared red meat to plant based protein. They found that one serving of red meat per day increased the risk for heart disease by 12%. One serving per day of unprocessed red meat increased the risk to 15%. Replacing red meat with plant-based protein lowered the risk for heart disease. If red meat was substituted with fish, yogurt, cheese or eggs, the risk of heart disease decreased by 15-24%. Replacing red meat with plant proteins was even more beneficial for those over 65 years old.  The bottom line was that increasing consumption of red meat proportionally increased the risk for heart disease. However, the key to a heart healthy diet may be less about reducing red meat and more about consuming plant based foods that protect the heart. We don’t know if the goal is eating less red meat or eating more plant based protein. 

 

What can be said about red meat consumption in 2021? It seems clear that processed red meats should be avoided. If unprocessed red meat is to be eaten, then limit consumption to about once per week.  It may be best to leave the ham to a once a year tradition.

 

Monday, December 14, 2020

The Vaccine


Has something been needling you the past year? Has something been jabbing at your brain? Has something pricked the bubble of your hopes and dreams for 2020? Of course! It’s COVID 19! Now, finally, there may be light at the end of the tunnel with the coronavirus vaccine. How does the new vaccine work and what does the data show?

 

Vaccines work by training the immune system to recognize and kill a foreign invader, such as a virus. Older vaccines work by injecting a dead virus or a weak live viruses to stimulate an immune response.  Newer vaccines work by injecting proteins found on the virus and teaching the immune system to mount a defensive response. Vaccines typically take years or even decades before they are ready to be used by the public. The development of a coronavirus vaccine is somewhat of a scientific miracle; the first COVID 19 case was described on December 1 2019, the coronavirus genetic code was sequenced on January 10 2020 and a vaccine was approved by the FDA on December 11 2020.  The coronavirus vaccine is not a single vaccine, there are at least six different methods companies are using to attack the virus.  Despite the quick turn around on the coronavirus vaccine, the technology behind it has been in development for decades. One method (the vaccine platform used by both Pfizer and Moderna) uses two key components: messenger RNA and the spike protein found on coronaviruses. Messenger RNA takes instructions encoded in the DNA into cells to turn on protein manufacturing. Messenger RNA vaccine technology was invented in the 1990’s and has been constantly refined since then. Work on a spike protein vaccine accelerated after pandemics with severe respiratory syndrome (SARS) in 2003 and Middle East respiratory syndrome (MERS) in 2012, viruses that are similar to coronavirus. The vaccine, containing messenger RNA in a lipid shell, works as follows. The messenger RNA carrying a copy of the spike protein enters a cell. The cell reads the instructions for the spike protein and starts making copies of it.  The spike protein moves to the outside of the cell where the immune system detects it. The immune system then learns how to recognize the protein and releases defense mechanisms to kill the infected cells. The second method uses a viral vector (AstraZeneca, Johnson and Johnson and Oxford use this approach). The coronavirus spike protein is introduced into an adenovirus that infects only chimpanzees. The vaccine contains an empty adenovirus with the spike protein inside. This is injected and stimulates the immune system to recognize the spike protein and mount an immune response. Both vaccines teach the body’s own immune system to find and kill the coronavirus.

 

The data on Pfizer’s messenger RNA vaccine was just reported.  The trial enrolled 43,448 people, all 16 years of age or older.  The vaccine was administered in two doses, 21 days apart and patients were followed for two months. The efficacy of the vaccine in preventing symptomatic COVID 19 was excellent at 95%. The efficacy was good for all groups: 94% for those over 55 years old, 96% for men, 94 % for women, 95% for whites, 100% for blacks, 94% for Hispanics and 94% for those with hypertension. For comparison, the efficacy of the measles vaccine is 97%, the chicken pox vaccine is 82% and the flu vaccine varies from 50% to 60%. Side effects were generally mild and included pain at the injection site, fever, fatigue, headache and muscle or joint pain.  In general, reactions were milder and less common in older patients (> 55) compared to younger patients.  Reactions were more common after the second dose compared to the first dose. Side effects are similar to the reactions seen after the shingles vaccine.  It is not known whether the vaccine can prevent COVID 19 in children under 16 years old, pregnant women and immunocompromised patients. In addition, the study could not determine whether the vaccine prevents asymptomatic infection. Lastly, patients in the placebo arm will have to be offered the vaccine since the FDA approved it. It is unethical to withhold vaccine for these people. This means that long-term efficacy and safety will be determined by real world experience. Based on this data, the FDA gave the Pfizer vaccine emergency use authorization on December 11 2020. The first dose of this vaccine was given to a 90-year-old woman in England on December 8 2020.  Moderna is conducting a 30,000 person trial with a similar vaccine. The preliminary results show good efficacy (also 95%) and safety but the final results are still pending. 

 

The Oxford adenovirus vector vaccine was studied in 23,849 people over the age of 18. This was also a two-dose regimen. The efficacy was 62% in patients who received two standard doses and 90% in those who received a low dose followed by a standard dose. The side effect profile was also very low.  Johnson and Johnson’s vaccine works in a similar fashion.  A 60,000 person trial was put on hold due to a serious adverse reaction but has recently resumed. Results from the trial are pending. 

 

To contain coronavirus, it is estimated that 60% of the population will need to be vaccinated to achieve herd immunity.  This may be difficult for several reasons. First, enough vaccine must be manufactured and distributed. There are many logistical obstacles. Next, enough people must consent to take the vaccine.  A recent poll of Americans found that 29% would definitely take the vaccine and 31% would probably take it. That adds up to 60% with no room for error. In addition, a poll among health care workers in New Jersey revealed only 50% were planning on taking the vaccine. This is disappointing since the CDC guidelines will have health care personnel vaccinated first along with long term nursing home residents in Phase 1a.  Phase 1b will be essential workers (police, fire, corrections officers, transportation workers, food and agriculture workers and teachers). Phase 1C will include adults with high-risk medical conditions and adults over age 65. 

 

Some caveats:

The efficacy of the vaccine is excellent (better than the annual flu vaccine with an efficacy of only 50-60%). 

It seems that the vaccine-induced immune response is stronger than that of the natural COVID 19 infection.

The side effect profile is similar to other vaccines (such as the shingles vaccine). 

The coronavirus is not being injected. You cannot get COVID 19 from the vaccine.

The vaccine will not alter your DNA.

 

So once it is available, please line up to get your vaccine. It will help your herd tremendously. 

 

 

Monday, November 16, 2020

New Jersey Just Legalized Marijuana. Is This Good News For the Heart?



The big news in this month's election is not the contested presidential race. It's not undecided Senate seats. The big news is that New Jersey voted to legalize recreational marijuana use! Is this a recreational activity that is good, or even safe, for those with heart disease or risks for heart disease?

 

Marijuana is a greenish mixture of leaves, stems, and flowers derived from Cannabis plants.  It contains many different chemicals, called cannabinoids.  The two major, active chemicals are delta 9-tetrahydrocannabinol (THC) and cannabidiol (CBD).  THC is the most psychoactive chemical, producing the euphoric effects of marijuana. CBD is anti-inflammatory. There are also synthetic cannabinoids which are used for medical purposes in the treatment of epilepsy and to relieve severe nausea and vomiting in cancer chemotherapy patients.  Cannabinoids are either smoked or eaten, with 77% of users reporting inhalation as their method of choice. There has been a dramatic increase in marijuana use over the last ten years.  In 2017, more than 39 million Americans reported using marijuana at least once.  Marijuana consumption is not just for the young. In the older population, marijuana is used to treat chronic illnesses.  Marijuana consumption increased by 4.5 times in people over age 55 between 2002 and 2014. 

 

Paralleling the increase in consumption is an increase in the legalization of marijuana at the state level.  The medical use of cannabis is legal (with a doctor’s prescription) in 35 states.  New Jersey legalized medical marijuana in 2010. The law allowed marijuana to be acquired at state licensed treatment centers. As of 2017, there were six centers in the state, with about 12,000 patients enrolled in the program.  On November 3 2020, New Jersey voted, by a 66% to 33% margin, to legalize the recreational use of marijuana, joining 14 other states. The law will take effect on January 1 2021, potentially opening a huge market (estimated at $2 billion) as New Jersey is the most populous state on the East Coast to legalize marijuana.

 

The general public opinion is that marijuana use is safe, maybe even healthy. How true is that assumption? What are the physiologic effects of marijuana? Is marijuana consumption safe for heart patients?  Smoking marijuana causes an immediate increase in heart rate and blood pressure as well as an increase in the work of the heart. In addition, it activates the body’s release of adrenaline. Marijuana impairs the blood’s oxygen carrying capacity, resulting in less oxygen to the heart muscle. Marijuana can cause inflammation and blood clots within the heart arteries. None of these effects are beneficial for heart patients.  Multiple case reports have linked marijuana with heart attacks and strokes.  The victims are usually young (average age 45), males, and without cardiac risk factors. The risk of a heart attack rises 5 fold within one hour of smoking marijuana.  Angina, chest pain, also occurs frequently after smoking marijuana due to the decrease in oxygen to the heart.   Cardiac rhythm problems may also occur with marijuana smoking, due to the stimulation by adrenaline.  The most common rhythm disturbances are atrial fibrillation (an irregular rhythm from the upper chambers of the heart) and ventricular fibrillation (cardiac arrest).  The average age of patients suffering from marijuana-associated arrhythmias is only 24 years old.  About 3% of marijuana users experience an arrhythmia. On the other end of the spectrum, at higher doses of THC, slow heart rates can occur, sometimes necessitating a pacemaker. Most of the effects described are with inhalation of marijuana. However edible forms are not safer and may be more dangerous. Oral marijuana gets into the blood stream slower than inhaled marijuana. Since the favorable psychogenic effects take longer, more is consumed, leading to higher concentration of chemicals and a higher rate of complications. Lastly, marijuana interacts with many cardiac medications including antiarrhythmic agents, calcium channel blockers, beta-blockers, statins and warfarin. 

 

While there is evidence linking marijuana to adverse cardiac events, the studies are not robust. Given the increasing use of marijuana in the general population as well as the population with heart disease or heart risks, high quality studies are needed. However, the adverse effects of marijuana seem to be as bad as cigarette smoke. It can be concluded that inhaling particulate matter of any kind is harmful to the heart and blood vessels. That’s food for your head before you go to the head shop in January 2021. 

  

Tuesday, October 20, 2020

Time Restricted Eating. Time for a Change?

 


Mediterranean, Pesco-Mediterranean, Keto, Paleo, Atkins, DASH, vegetarian, lacto- vegetarian, ovo-vegetarian, vegan. There are a staggering number of diets, but which one is right? Each has their proponents and their opponents. All of these diets tout weight loss, cholesterol lowering, prevention of heart disease and longevity. Unfortunately, the research behind the claims of these diets is shaky. Nutritional research is plagued by poorly conducted scientific studies. What is lacking in dietary studies? First, the method used by most studies is an observational model rather than the more rigorous randomized controlled trial. In addition, outcomes such as heart disease or death take a long time to develop, so diet studies must be carried on for years to see a possible effect. Lastly, nutritional studies are often funded by industry and thus subject to bias. It is therefore very difficult to recommend a particular diet, with scientific certainty, to promote health and reduce heart disease. However, what if the key to health lies not in the food we eat, but in not eating at all?

 

Of course we need to eat to survive and to live a long and healthy life. However the benefits of fasting have recently come into focus.  Early in the course of human evolution, energy rich food was not always available. We evolved to handle periods of feast and famine. We adapted by storing energy as fat. During times of fasting, the stored fat was metabolized into energy.  Nowadays, with the round-the-clock availability of energy dense food coupled with inactivity, fat stores in the body grow, are not mobilized and obesity, diabetes, heart disease and early death are the result. Not eating, fasting, may be a good thing. In fact, many studies have shown that reduced calorie intake over the course of a lifetime, increases the life span. For example, the exceptional longevity of the people on Okinawa can be partially attributed to a constant low level of calorie intake. 

 

Three types of fasting have been studied: alternate day fasting, 5:2 fasting (fasting 2 days per week) and time restricted eating. Time restricted eating, limiting the intake of calories to a short window between six and twelve hours per day, is the best studied and the most in vogue in the medical literature.  This strategy is attractive in that it does not require time consuming measurements and adherence to a strict diet. After a twelve hour overnight fast, the body mobilizes fat stores. This decreases intra-abdominal fat tissue and leads to weight loss. The stress of fasting challenges the body to come up with ways to tolerate or overcome the period of fasting. Most of the organs in the body are able to do this. With repeated bouts of fasting, these adaptive changes allow the body to resist a broad range of potentially damaging stresses. Fasting does stress the body, but low levels of stress are good.  Consider the analogy with exercise. Everyone agrees that exercise stresses the body and can make people feel uncomfortable. No Pain No Gain! However that stress produces positive benefits by improving fitness, helping with weight loss, lowering blood pressure, decreasing the risk for diabetes and heart disease.  If the stress of exercise is good, so too is the stress of fasting. Time restricted eating has been shown to prevent obesity as well as lower blood pressure, decrease heart rate, lower cholesterol and triglycerides, reduce inflammation and prevent diabetes.  In addition, intermittent fasting may prevent dementia. In trials with older adults, intermittent fasting improved memory. Whether these beneficial effects translate into a lower risk for heart disease and death has not yet been determined. 

 

There are downsides to time restricted eating. First, the timing of meals is often dictated by work schedule or cultural norms or even weather (Mediterranean countries often eat at 9 or 10 PM, after the sun is down and it is cooler). In addition, fasting for prolonged periods makes people jittery and irritable. It makes them hangry! We have to rationalize that that uncomfortable feeling does stress the body, but it produces positive adaptations. Intermittent fasting results in weight loss. However the amount of weight lost is similar to the weight loss on a reduced calorie diet. Fasting can lead to the loss of muscle mass and bone density in people who are not obese. In fact, the overall effects of intermittent fasting in nonobese patients is not known. Lastly, the studies on time restricted eating were mostly in animals, with some observational human trials. In addition, no studies have determined the optimal time window for eating. Clearly more research is needed before the widespread prescription of time restricted eating. 

 

Until further research is done, what recommendations can be made?  Certainly an easy adaptation would be to restrict food intake to a tight window. There are a couple of possible options. One is unrestricted eating but only between 9 AM and 6 PM, with no nighttime snacking. The other approach is eating only between 12 PM and 8 PM, while skipping breakfast. Both methods provide more than a twelve-hour window of fasting.  In addition, restricting total calories intake is always a good recommendation. Remember: Eat less, live longer