Sunday, April 29, 2012

The Nutrition Debate #50: Free Radicals and Oxidative Stress

In The Nutrition Debate #46, we posited that oxidative stress was one of the three prime contributors to cardiovascular disease, along with inflammation and imbalances in blood sugar and insulin. But, what is oxidative stress and what causes it? Oxidative stress is an imbalance between the production of reactive oxygen species (ROS) and the body’s ability to neutralize them. Thus, a delicate balance is required. Too many reactive oxidizing species or too few (or ineffective) anti-oxidant defenses produce oxidative stress. And oxidative stress can lead to atherogenesis, etc., etc.
Free Radicals are one of the most common ROS. They have an unpaired electron that makes them highly reactive chemically, but also generally short-lived. The long-lived free radicals can be dangerous, depending on their stability. According to Wikipedia, “Excessive amounts of these free radicals can lead to cell injury and death, which may contribute to many diseases such as cancer, stroke, myocardial infarction and diabetes. Many forms of cancer are thought to be the result of reactions between free radicals and DNA, potentially resulting in mutations that can adversely affect the cell cycle and potentially lead to malignancy.”
Some of the symptoms of aging such as atherosclerosis are also attributed to free-radical induced oxidation of many of the chemicals in the body. In addition, free radicals contribute to alcohol-induced liver damage, perhaps more than alcohol itself. Radicals in cigarette smoke are implicated in the process that promotes the development of emphysema.
But, free radicals play an important role in a number of biological processes, and “some of these are necessary for life such as the intracellular killing of bacteria by… macrophages,” according to Wikipedia. See column #48. So, because some free radicals are necessary for life, the body produces a number of enzymes to minimize free radical-induced damage and to repair damage that does occur. In addition, antioxidants play a key role in these defense mechanisms. Research is underway to determine the relative importance and interactions between antioxidants. In the meantime the use of antioxidant supplements to prevent disease is very controversial; real food sources are probably the best choices and very tasty too.
Antioxidants are classified into two broad divisions, depending on whether they are water soluble or fat soluble. These compounds may be synthesized in the body or obtained from the diet or through supplementation. Some are mostly present within cells, while others, such as uric acid, are more evenly distributed. In fact, human blood has a high concentration of water-soluble uric acid. Antioxidants are found in vegetables, fruits, grains, eggs, meat, legumes, and nuts. Herbs and spices are particularly high in antioxidants.
·         Vitamin C (ascorbic acid): Bell pepper, parsley, broccoli, Brussels sprouts, cauliflower, kale (see list here).
·         Vitamin E (tocopherols, tocotrienols): green leafy vegetables, almonds, asparagus, papaya (see list here).
  • Polyphenolic antioxidants (flavonoids): tea, coffee, fruit, olive oil, chocolate, red wine, and herbs and spices  (top 10 list here).  Also, see this 2002 Science Daily reprint from the American Chemical Society.
·         Carotenoids (lycopene, carotenes, lutein): sweet potatoes, spinach, tomatoes,  and chili peppers (see list here).
In general, processed foods contain fewer antioxidants than fresh and uncooked foods, since generally the preparation process exposes the food to oxygen.
Again, Wikipedia: “The paradox in metabolism is that, while the vast majority of complex life on Earth requires oxygen for its existence, oxygen is a highly reactive molecule that damages living organisms by producing reactive oxygen species. Consequently, organisms contain a complex network of antioxidant metabolites and enzymes that work together to prevent oxidative damage to cellular components such as DNA, proteins and lipids. In general, oxidant systems either prevent these reactive species from being formed, or remove them before they can damage vital components of the cell. However, reactive oxygen species also have useful cellular functions, such as redox signaling. Thus the function of antioxidant systems is not to remove oxidants entirely, but instead to keep them at an optimum level.” The oxidative challenge in biology is to maintain proper cellular homeostasis -- a balance between reactive oxygen production and consumption. Diet and lifestyle play a large role in this complex system… and you are in charge.
 © Dan Brown 4/29/12

Sunday, April 22, 2012

The Nutrition Debate #49: The Dietary Causes of Inflammation

Do you have syphilis? Or snort cocaine, or smoke tobacco, or have a bacterial infection or periodontal disease that causes overproduction of cholesterol that accumulates in the arteries? If none of these “insults” apply to your body, the cause of chronic inflammation, and therefore the cause of atherosclerotic plaque in your arteries, is likely to be dietary.
The relationship between dietary fat and atherosclerosis, however, is a contentious field. The USDA, in its food pyramid and Dietary Guidelines for Americans, promotes a low-fat diet, based largely on the view that fat in the diet is atherogenic. The American Heart Association, the American Diabetes Association and the National Cholesterol Education Program make similar recommendations. Especially singled out are saturated fats, dietary cholesterol and trans fats.  Trans fats are one of the few consensus points in nutrition as everyone thinks these are very bad for your health. But could all of these authorities be wrong about the role of saturated fats and dietary cholesterol?
In a word, “yes.” Writing in Science, multiple award-winning science writer Gary Taubes says that political considerations played into the recommendation of government bodies. Gary Taubes broke onto the scene with his 2002 exposé in the New York Times Sunday magazine cover story, “What if it’s All Been a Big Fat Lie?” Later he wrote a tome for serious readers, “Good Calories – Bad Calories” and later still a more readable “Why We Get Fat – And What to Do About It.”
Professor Walter Willett, of the Harvard School of Public Health and Principal Investigator of the second Nurse’s Health Study, recommends much higher levels of dietary fat than the public health establishment, and especially of monounsaturated and polyunsaturated fat. Once again, there is growing unanimity that monounsaturated fats, such as are found in olive oil, are healthy. But polyunsaturated fats, such as are found in vegetable and seed oils, are coming under increasing scrutiny. Soy bean oil and corn oil are the most widely used, accounting for over 90% of food oils used in the U.S.
Unfortunately, polyunsaturated fats are not particularly stable. They become damaged or oxidized very easily. Oxidized or rancid fats play a very troubling role. Feed rancid fats to lab rats and they will develop atherosclerosis. In another study, rabbits fed atherogenic diets containing various seed and grain oils showed the largest increase in oxidative susceptibility of LDL. In a study involving rabbits fed heated soybean oil, “grossly induced atherosclerosis and marked liver damage were histological and clinically demonstrated,” as per Wikipedia.
Rancid fats and oils taste and smell very bad even in small amounts and people avoid eating them. But, in the United States, the majority of oils consumed are refined, bleached, deodorized and degummed by manufacturers. The resultant oils are colorless, odorless, tasteless, and have a longer shelf life than their unrefined counterparts. This extensive processing makes fully oxidized, rancid oils much more elusive to detection via human senses.
To properly protect polyunsaturated fats (vegetable and seed oils) from oxidation, it is best to keep them cool and in a dark and oxygen free environment. And don’t overheat or use them repeatedly, such as in deep fat frying. I keep my Omega-3 fish oil capsules and Flax Oil (very high in Omega-3s) in the refrigerator. I also keep Safflower Oil, another polyunsaturated fatty acid (PUFA), which I use with olive oil and coconut oil to make mayonnaise, in the refrigerator.
So, if atherosclerosis is defined by Wikipedia as “a chronic inflammatory response in the walls of arteries, promoted by LDL…without adequate removal of fats and cholesterol…by…HDL,” then we should be concerned about the quality and quantity of LDL in our arteries – lest it become oxidized LDL. Likewise, we should be concerned if our circulating HDL in not high enough to transport any oxidized-LDL back to the liver the way it is supposed to.
Why do these two conditions (high LDL and low HDL) co-exist in so many of us today? It’s the diet of course. To avoid oxidized LDL, we can begin by eating far fewer polyunsaturated fats, especially ones that are hydrogenated, oxidized, or overheated. We can also take supplementary Omega-3s to help us regain a better Omega 6/Omega 3 balance. Then, we can significantly raise our HDL so they can do their job. See The Nutrition Debate #34 for “Foods that Raise HDL.”
The oxidized-LDL hypothesis posits that, “Once inside the vessel wall, LDL molecules become susceptible to oxidation by free radicals and become toxic to the cells.” (See The Nutrition Debate #48) Free radicals cause the oxidative stress that “triggers a cascade of immune responses which over time can produce an atheroma, the characteristic nodule in the artery wall that is the start of atherosclerosis. “Free Radicals and Oxidative Stress” is the subject of the next column.                           
 © Dan Brown 4/21/12

Sunday, April 15, 2012

The Nutrition Debate #48: Inflammation and Atherosclerosis

“Atherosclerosis…is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol. It is a syndrome affecting arterial blood vessels, a chronic inflammatory response in the walls of arteries, caused largely by the accumulation of macrophage white blood cells and promoted by low-density lipoproteins (LDL) -- plasma proteins that carry cholesterol and triglycerides -- without adequate removal of fats and cholesterol from the macrophages by…high-density lipoproteins (HDL)” (all italics added).  So begins the Wikipedia entry on Atherosclerosis.
Atherosclerosis is a chronic disease that remains asymptomatic for decades. Atherosclerotic lesions, or plaques, cause narrowing (stenosis) of the artery and, if unstable, can rupture and induce a thrombus (blood clot, attached or motile). A thrombus, in place or more likely downstream, can cause an occlusion of the lumen of the artery, stopping blood flow (ischemia), resulting in the death of tissues fed by the artery. This catastrophic event is called infarction. Thrombosis in the coronary artery is a myocardial infarction (heart attack). Stroke is often caused by a clot in the carotid artery.
These complications of advanced atherosclerosis are chronic, slowly progressive and cumulative. What’s “new” in the understanding of atherosclerosis, however, is an appreciation of the role of inflammation in atherosclerosis. The 2002 abstract of a paper titled “Inflammation and Atherosclerosis” begins, “Atherosclerosis, formerly considered a bland lipid storage disease, actually involves an ongoing inflammatory response.” The full paper was published in Circulation (2002; 105:1135-1143), the Journal of the American Heart Association, under the banner “Clinical Cardiology: New Frontiers.”
The main cause of atherosclerosis is yet unknown, but a considerable body of experimental evidence points to oxidized LDL. This hypothesis posits that the inflammatory processes in the artery wall are initiated in response to retained low-density lipoprotein (LDL) molecules. The LDL molecule is globular shaped with a hollow core whose purpose is to carry cholesterol throughout the body. Once inside the vessel wall, LDL molecules become susceptible to oxidation by free radicals, and become toxic to the cells. The damage caused by the oxidized LDL molecules triggers a cascade of immune responses which over time can produce an atheroma, the characteristic nodule in the artery wall.
The body’s immune system responds to the damage to the artery wall by sending specialized white blood cells (macrophages and T-lymphocytes) to absorb the oxidized-LDL forming specialized foam cells. These white blood cells are not able to process the oxidized-LDL, and ultimately grow, then rupture, depositing a greater amount of oxidized cholesterol into the artery wall. This triggers more white blood cells, continuing the cycle, according to the theory. The primary documented driver of this process is therefore oxidized-LDL particles within the artery wall.
According to Wiki, various anatomic, physiological and behavioral risk factors for atherosclerosis are known. They can be divided into the categories modifiable or not. The points labeled ‘+’ in the list below form the core components of Metabolic Syndrome, discussed in multiple columns in The Nutrition Debate, starting with column #9.
·         Diabetes or Impaired glucose tolerance (IGT) +
·         Dyslipoproteinemia (unhealthy patterns of serum proteins carrying fats and cholesterol, such as) +
o   High LDL (bad if elevated and small/dense particles) and/or High VLDL
o   Low HDL (protective if large/fluffy particles and high enough)
o   An LDL:HDL ratio great than 3:1
·         Elevated serum C-Reactive Protein concentrations
·         Hypertension +, on its own increasing risk by 60%
·         Vitamin B6 deficiency
·         Tobacco smoking, increases risk by 200% after several pack years
·         Periodontal disease
Non-modifiable risk factors include advanced age, male sex, having close relatives who have some complication of atherosclerosis (e.g. coronary heart disease or stroke), and genetic abnormality, e.g. familial hypercholesterolemia.
Other lesser or uncertain risk factors for atherosclerosis includes obesity +, a sedentary lifestyle, hypercoagulability, post-menopausal estrogen deficiency, high intake of saturated fat (may raise total and LDL cholesterol), intake of trans fats (may raise total and LDL cholesterol while lowering HDL), high carbohydrate intake, elevated triglycerides +, homocysteine, uric acid, or fibrinogen or lipoprotein(a) concentrations, chronic systemic inflammation, as reflected by upper normal WBC concentrations, elevated hs C-reactive protein or serum insulin levels +, stress or symptoms of clinical depression, hyperthyroidism (over-active thyroid), short sleep duration and Chlamydia pneumoniae infection. That only leaves dietary causes of inflammation that cause atherosclerotic plaque, the subject of the next column.

© Dan Brown 4/15/12

Sunday, April 8, 2012

The Nutrition Debate #47: Testing for Heart Disease Risk

“Key tests can reveal problems with a person’s blood sugar and insulin, inflammation level, level of folic acid, clotting factors, hormones and other bodily systems that affect your risk of cardiovascular disease,” says Mark Hyman, MD, the Lennox, MA, practitioner, on a May 2010 blog post.  This last-of-three column on that post will discuss some of these tests and zero in on these prime markers for cardiovascular disease.
“There’s no doubt about it,” Dr. Hyman says, “Inflammation is a key contributor to heart disease. A major study done at Harvard found that people with high levels of a marker called C-Reactive Protein (hs-CRP) had higher risks of heart disease than people with high cholesterol. Normal cholesterol levels were NOT protective to those with high CRP. The risks were greatest for those with high levels of both CRP and cholesterol.”
“Another predisposing factor to heart disease is insulin resistance or metabolic syndrome, which leads to an imbalance in the blood sugar and high levels of insulin. This may affect as many as half of Americans over age 65. Many younger people also have this condition, which is sometimes called pre-diabetes,” says Dr. Hyman.
“Although modern medicine sometimes loses sight of the interconnectedness of all our bodily systems, blood sugar imbalances like these impact your cholesterol levels too. If you have any of these conditions, they will cause your good cholesterol to go down, while your triglycerides rise, which further increases inflammation and oxidative stress. All of these fluctuations contribute to blood thickening, clotting, and other malfunctions – leading to cardiovascular disease.”
“What’s more, elevated levels of a substance called homocysteine (related to our body’s levels of folic acid and vitamins B6 and B12) appear to correlate to cardiovascular illness. Where problematic levels occur, they can be easily addressed by adequate folic acid intake, along with vitamins B6 and B12.” My own internist, who is also a board-certified cardiologist, has had me on a supplement called Homocysteine Modulators (Solgar brand), as well as CoQ10, for years.
“So, heart disease is not only about cholesterol. It is important to look at many factors that contribute to your overall risk.” Dr. Hyman notes, “It seems that insulin and blood sugar imbalances and inflammation are proving to be more of a risk than cholesterol.” If you want to test your overall risk, consider asking your doctor to perform the following tests:
·         Cardio (hs) CRP (C-Reactive Protein): There can be many causes of inflammation in the body, but this marker of inflammation is essential to understand in the context of overall risk. Your CRP should be less than 1.0.
·         Standard Lipid Panel: Total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides. Pay particular attention to your HDL and triglycerides and the TC/HDL and TG/HDL ratios and work to improve them.  Pay less attention to lowering Total Cholesterol by lowering LDL, an outcome shown to be of dubious value alone. Your doctor can’t write a script for raising HDL and lowering triglycerides. You have to do it yourself by the food choices you make each and every meal.
·         VAP cholesterol test: directly measures LDL (vs. calculated as in the standard lipid test above), also VLDL, LP(a), and LDL particle size and characteristics (small, dense vs. large, fluffy).
·         Hemoglobin (Hb) A1c: This measures your average blood sugar over the last 6 weeks to 3 months. Anything over 5.5 is high. Dr. Richard K. Bernstein, the glucose self-testing guru and leading diabetes expert, considers 5.8 to be full-blown diabetes. Alas, the ADA considers 6.5 (formerly 7.0) to be diabetes and 6.0 to be pre-diabetes. Studies show that CVD risk doubles from an A1c of 5.5 to 6.0.
·         Glucose Insulin Tolerance Test: Measurements of fasting and 1 and 2 hour levels of glucose AND insulin helps identify pre-diabetes and excessively high levels of insulin. Most doctors just check blood sugar and NOT insulin, which is the first thing to go up. By the time your blood sugar goes up, “the train has left the station.”
·         Homocysteine: Your homocysteine measures your folate status and should be between 6 and 8.
·         Fibrinogen: Looks at clotting factors in the blood. It should be less than 300.
And, most importantly, know your test results. Take charge of your health. It’s your life. Make the most of it.

© Dan Brown 4/8/12

Sunday, April 1, 2012

The Nutrition Debate #46: How to Treat Heart Disease Risk (a doctor’s prescription)

If lowering LDL and therefore Total Cholesterol is not the great panacea that we thought, how does one treat heart disease risk? “How do we get the right kind of cholesterol – high HDL, low LDL and low triglycerides, and have cholesterol particles that are large, light and fluffy rather than small, dense and hard, which is the type that actually causes heart disease and plaque build-up,” asks Mark Hyman, MD, in a May 2010 blog post, found at

Again, according to Dr. Hyman, “We know what causes the damaging small cholesterol particles. And it’s not fat in the diet. It is sugar. Sugar in any form or refined carbohydrates (white food) drives the good cholesterol down, causes triglycerides to go up, creates small damaging cholesterol particles, and causes metabolic syndrome or pre-diabetes. That is the true cause of most heart attacks, NOT LDL cholesterol.”

“One of the reasons we don’t hear about this is because there is no good drug to raise HDL. Statin drugs lower LDL – and billions are spent advertising them, even though they are the wrong treatment. If you are like most of the patients I see in my practice,” Dr. Hyman says, “you’re convinced that cholesterol is the evil that causes heart disease. You may hope that if you monitor your cholesterol levels and avoid the foods that are purported to raise cholesterol, you’ll be safe from America’s number-one killer. If only it were so simple,” he says. “The truth is much more complex. Cholesterol is only one factor of many – and not even the most important – that contributes to your risk of getting heart disease,” he says.

According to Dr. Hyman (and many, many other cutting-edge practitioners), the three prime contributors to cardiovascular disease are: 1) inflammation, 2) imbalances in blood sugar and insulin, and 3) oxidative stress. “To control these key biological functions and keep them in balance, you need to look at your overall health as well as your genetic predispositions, as these underlie the types of diseases you’re most likely to develop. It is the interaction of your genes, lifestyle, and environment that ultimately determines your risks – and the outcome of your life,” Dr. Hyman says.

“This is the science of nutrigenomics, or how food acts as information to stall or totally prevent some predisposed disease risks by turning on the right gene messages with our diet and lifestyle choices. That means some of the factors that unbalance bodily health are under your control, or could be. These include nutritional status, stress levels and activity levels” (italics added). Nutritional status means the foods you choose to eat. They are under your control. Get it?

To demonstrate the effect of diet on nutritional status, I offer my own test results (n = 1) as an example. I previously reported this in “The Nutrition Debate #34: Foods that Raise HDL,” on my blog. You can access this and all other columns at The Nutrition Debate. Before I started eating low-carb 10 years ago, my average HDL over the previous 22 years was 43mg/dl. The desired range for men is ≥ 40mg/dl and for women ≥ 50mg/dl. My average HDL now is 78mg/dl. My most recent HDL was 92mg/dl. Bonus. There seems to be a link between HDL and longevity in men. Check out this link from The American Journal of Cardiology posted in Newsmax Health :

Before I started low-carbing, my triglyceride average of 21 previous tests was 137. The desired range for both men and women is < 150mg/dl. My triglyceride average for the most recent 21 tests is 54. My most recent was 32mg/dl. My ratio of triglycerides to HDL is 0.35 (ideal range is < 1.0). My ratio of Total Cholesterol to HDL is 2.3 (209/92). Desired range is < 5.0. My doctor says “just keep on doing what you’re doing.” It’s fun (for both) to visit his office. No more hectoring.

As for inflammation, the most statistically significant marker for overall heart disease risk is the hs (high sensitivity) cardio C-Reactive Protein test (hs-CRP). Your C-Reactive Protein level should be less than 1.0. At the time I started low-carbing, mine was 5.8. My most recent was 1.5. It has been as low as 0.7. I’m obviously doing something wrong, and I’ve still got some work to do to figure out what it is. Hey doc (my doctor, not Dr. Hyman): What extra tests can you do to help me figure out whether this low-grade inflammation is acute or chronic, and if chronic (as is likely), the source?

© Dan Brown 4/1/12