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Ketogenic Diets: Possible Hidden Cardiovascular Risks?
Bodybuilders and Cardiovascular Health
Cardiovascular health is important for bodybuilders and anabolic steroid-using athletes to consider, as certain anabolic-androgenic steroids (AAS) are associated with adverse changes in cholesterol, and heart attacks and heart failure are some of the most common causes of sudden death or serious injury in this group. Elite bodybuilders and many other AAS users have suffered heart problems. While it is not possible to directly assign AAS as a contributing cause to these cases, there is a strong base building due to several reasons:
• Use patterns of AAS— dose and duration of cycles— have changed.
• Polypharmacy (the use of multiple medications and/or the administration of more medications than are clinically indicated, representing unnecessary drug use) includes many other anabolic biologics (growth hormones and cytokines) and potent lipolytics (fat-reducers).
• The demographics of AAS users are aging.
‘Cardiovascular’ refers to the heart and the blood vessels. Heart damage is most commonly caused by ischemia (oxygen deprivation) but can also be electrical in nature, as the heartbeat is generated by an internal conduction system that accelerates and decelerates to meet the circulatory demand of the body. When the electrical signal is disrupted, the heart does not beat efficiently or if the disruption is severe enough, may not beat at all. Ischemic damage of the heart (and brain, as well as other tissues) is often due to a buildup of plaque in the arteries, but may also be due to inappropriate vasoconstriction (the blood vessel squeezing shut, as seen in the skin when exposed to cold) or not dilating (opening wider) when oxygen demand requires greater blood flow. Many abusers of cocaine suffered heart attacks due to coronary vasoconstriction, even though their arteries were perfectly healthy.7
When ischemia is mild-to-moderate and long-term, the body grows new blood vessels to shorten the distance between active cells and nearby capillaries (the smallest blood vessels and the site where oxygen and factors are diffuse back-and-forth to cells of the body).8 A person who lives in the mountains likely has a higher capillary density (a measure of how branched the circulation is to provide oxygen) than a person who lives on the beach at sea level. Many endurance athletes sleep in special chambers that mimic living in the mountains. This increases their red blood cell supply (the cells that carry oxygen) by stimulating the hormone erythropoietin, and likely stimulates new blood vessel growth. Many cancer drugs kill tumors by shutting down blood vessel growth, starving the malignant tumors of oxygen and nutrients.9
One final mechanism that affects the buildup of plaque in artery walls is the ability of the blood vessel to maintain an intact lining. Major blood vessels are designed not to leak, and do so by having a lining that prevents red and white blood cells from escaping into the surrounding tissue. With the constant flow of blood rushing through the vessels, the lining wears away but is constantly replaced by new lining cells. If these replacement cells were not available, plaque can more easily build up under the lining in the artery walls.
Picture a pickup truck bed with a spray-on liner. If the liner gets gouged, rust can develop in the underlying metal— unless a new layer of spray-on lining covers the damage. If neglected, the rust spreads, potentially causing significant damage.
Low-Carb Mice and Ketogenic Diets
This background is provided to put into context the relevance of a newly-published study that unveils some heretofore-unrealized concerns about ketogenic diets. A group of researchers at Beth Israel Hospital and other facilities, all part of the Harvard Medical System, compared the cardiovascular effect of three types of diets— all containing the same amount of cholesterol— in mice bred to be capable of developing atherosclerosis (plaque buildup).10 The standard chow was low in fat and protein, being 65 percent carbohydrate. The second group received a diet that mimics what most people in the United States consume, (43/15/42— carbohydrate/protein/fat); and the last group was provided with a low-carbohydrate diet of 12/45/43 (carbohydrate/protein/fat).
Mice do not develop atherosclerosis naturally, and the mice fed the standard ‘mouse chow’ had clean arteries after 12 weeks. Mice fed the Western diet had a significant amount of atherosclerosis and the low-carb mice had even more, nearly twice as much.
In looking at the typical lab markers to explain these findings, researchers discovered that there was no real difference in cholesterol, bad cholesterol, or oxidized cholesterol between mice fed the Western and low-carbohydrate diets. Both had a four-fold increase in serum (blood) cholesterol compared to the standard diet. The low-carbohydrate diet was not associated with any increase in oxidative damage (the molecular damage that is protected against by antioxidants). Oxidative damage is proposed to make blood vessels more susceptible to atherosclerosis.11
Another factor involved in atherosclerosis is inflammation. The study looked at two measures of inflammation and found the exact opposite of what would be expected. The low-carbohydrate diet resulted in lower measures of a specific marker for inflammation in the bloodstream— no different from measurements taken from mice fed the standard diet who had essentially no atherosclerosis.10
The mice fed the low-carbohydrate diet experienced a dramatic decrease in the healing ‘replacement cells’ that normally repair the blood vessel lining. The degree of decrease was greater than 80 percent and also affected precursor cells in the bone marrow.10 Ironically, one hormone that stimulates the production of the replacement cells, VEGF, actually increased in low-carbohydrate fed mice.10,12 Failing to directly measure the replacement cells (called endothelial progenitor cells, or EPC) and measuring VEGF instead would misled a clinician to believe that low-carbohydrate dieting was safer for cardiovascular health. The increase in VEGF may be a sign of the body reacting to the EPC-lowering effect of the low-carbohydrate diet in the mice.
EPC plays a role in new blood vessel growth, and corresponding to the decrease seen with EPC, low-carbohydrate fed mice were unable to respond to ischemia (oxygen deprivation).10,13 One of the factors known to stimulate EPC growth (pAkt) is a ‘downstream’ molecule in the insulin-signaling cascade. ‘Downstream’ means insulin turns on one molecule, which turns on another, which turns on pAkt. Statin drugs (Lipitor, for example), exercise, and estrogen have been shown to counteract impaired EPC production.13 Low-carbohydrate fed mice had significantly lowered insulin concentrations compared to other diets, as would be expected. Type 2 diabetics who are insulin-resistant also demonstrated impaired EPC production.14 Though this is not the entire reason EPC growth is impaired in low-carbohydrate diets, it likely plays a role.
Thus far, low-carbohydrate diets have been shown to markedly increase atherosclerosis, even compared to high-fat diets. This is in a setting that would not raise suspicion. In fact, many measures suggest that cardiovascular health is improved with low-carbohydrate dieting. Also, the ability of the circulatory system (blood vessels) to respond to oxygen deprivation is seriously impaired.
This study did not look at ketogenic dieting, as the carbohydrate content was high enough to prevent ketosis. Thus, it is difficult to determine whether the same concerns would be present during ketogenic dieting. However, another concerning observation has been noted during ketogenic dieting that adds another level of risk.
One study published last year showed that people on a ketogenic diet had impaired dilation, whereas those on a low-fat diet actually demonstrated improved flow-mediated dilation and response to a dilating drug. Similar impairment is again seen in people with insulin resistance.15,16 This adverse effect may be exaggerated when saturated fat is high, but the balance of research appears to suggest that if mono- and polyunsaturated fats are consumed in sufficient quantities and saturated fats are moderated, blood vessels should respond more appropriately to dilating signals.17 Research looking at non-ketogenic, low-carbohydrate diets do not demonstrate the same defect, suggesting there may be different risks present during ketosis.18-20
Given the findings in this study, it is impossible to recommend low-carbohydrate or ketogenic diets to those with a significant personal or family history of cardiovascular disease. In fact, this data supports the recommendation for moderate carbohydrate intake sufficient to maintain a baseline insulin presence. The exact recommendation for carbohydrates remains fuzzy at this time, but it appears that at least 60-100 grams per day of low-glycemic carbohydrates, along with an intake of mono- and polyunsaturated fats to counterbalance saturated fat intake, is the optimal diet plan. Excessive carbohydrate intake should be avoided as well, suggesting that the age-old adage of moderation in all things remains sound advice.
Bodybuilders and Cardiovascular Health
Cardiovascular health is important for bodybuilders and anabolic steroid-using athletes to consider, as certain anabolic-androgenic steroids (AAS) are associated with adverse changes in cholesterol, and heart attacks and heart failure are some of the most common causes of sudden death or serious injury in this group. Elite bodybuilders and many other AAS users have suffered heart problems. While it is not possible to directly assign AAS as a contributing cause to these cases, there is a strong base building due to several reasons:
• Use patterns of AAS— dose and duration of cycles— have changed.
• Polypharmacy (the use of multiple medications and/or the administration of more medications than are clinically indicated, representing unnecessary drug use) includes many other anabolic biologics (growth hormones and cytokines) and potent lipolytics (fat-reducers).
• The demographics of AAS users are aging.
‘Cardiovascular’ refers to the heart and the blood vessels. Heart damage is most commonly caused by ischemia (oxygen deprivation) but can also be electrical in nature, as the heartbeat is generated by an internal conduction system that accelerates and decelerates to meet the circulatory demand of the body. When the electrical signal is disrupted, the heart does not beat efficiently or if the disruption is severe enough, may not beat at all. Ischemic damage of the heart (and brain, as well as other tissues) is often due to a buildup of plaque in the arteries, but may also be due to inappropriate vasoconstriction (the blood vessel squeezing shut, as seen in the skin when exposed to cold) or not dilating (opening wider) when oxygen demand requires greater blood flow. Many abusers of cocaine suffered heart attacks due to coronary vasoconstriction, even though their arteries were perfectly healthy.7
When ischemia is mild-to-moderate and long-term, the body grows new blood vessels to shorten the distance between active cells and nearby capillaries (the smallest blood vessels and the site where oxygen and factors are diffuse back-and-forth to cells of the body).8 A person who lives in the mountains likely has a higher capillary density (a measure of how branched the circulation is to provide oxygen) than a person who lives on the beach at sea level. Many endurance athletes sleep in special chambers that mimic living in the mountains. This increases their red blood cell supply (the cells that carry oxygen) by stimulating the hormone erythropoietin, and likely stimulates new blood vessel growth. Many cancer drugs kill tumors by shutting down blood vessel growth, starving the malignant tumors of oxygen and nutrients.9
One final mechanism that affects the buildup of plaque in artery walls is the ability of the blood vessel to maintain an intact lining. Major blood vessels are designed not to leak, and do so by having a lining that prevents red and white blood cells from escaping into the surrounding tissue. With the constant flow of blood rushing through the vessels, the lining wears away but is constantly replaced by new lining cells. If these replacement cells were not available, plaque can more easily build up under the lining in the artery walls.
Picture a pickup truck bed with a spray-on liner. If the liner gets gouged, rust can develop in the underlying metal— unless a new layer of spray-on lining covers the damage. If neglected, the rust spreads, potentially causing significant damage.
Low-Carb Mice and Ketogenic Diets
This background is provided to put into context the relevance of a newly-published study that unveils some heretofore-unrealized concerns about ketogenic diets. A group of researchers at Beth Israel Hospital and other facilities, all part of the Harvard Medical System, compared the cardiovascular effect of three types of diets— all containing the same amount of cholesterol— in mice bred to be capable of developing atherosclerosis (plaque buildup).10 The standard chow was low in fat and protein, being 65 percent carbohydrate. The second group received a diet that mimics what most people in the United States consume, (43/15/42— carbohydrate/protein/fat); and the last group was provided with a low-carbohydrate diet of 12/45/43 (carbohydrate/protein/fat).
Mice do not develop atherosclerosis naturally, and the mice fed the standard ‘mouse chow’ had clean arteries after 12 weeks. Mice fed the Western diet had a significant amount of atherosclerosis and the low-carb mice had even more, nearly twice as much.
In looking at the typical lab markers to explain these findings, researchers discovered that there was no real difference in cholesterol, bad cholesterol, or oxidized cholesterol between mice fed the Western and low-carbohydrate diets. Both had a four-fold increase in serum (blood) cholesterol compared to the standard diet. The low-carbohydrate diet was not associated with any increase in oxidative damage (the molecular damage that is protected against by antioxidants). Oxidative damage is proposed to make blood vessels more susceptible to atherosclerosis.11
Another factor involved in atherosclerosis is inflammation. The study looked at two measures of inflammation and found the exact opposite of what would be expected. The low-carbohydrate diet resulted in lower measures of a specific marker for inflammation in the bloodstream— no different from measurements taken from mice fed the standard diet who had essentially no atherosclerosis.10
The mice fed the low-carbohydrate diet experienced a dramatic decrease in the healing ‘replacement cells’ that normally repair the blood vessel lining. The degree of decrease was greater than 80 percent and also affected precursor cells in the bone marrow.10 Ironically, one hormone that stimulates the production of the replacement cells, VEGF, actually increased in low-carbohydrate fed mice.10,12 Failing to directly measure the replacement cells (called endothelial progenitor cells, or EPC) and measuring VEGF instead would misled a clinician to believe that low-carbohydrate dieting was safer for cardiovascular health. The increase in VEGF may be a sign of the body reacting to the EPC-lowering effect of the low-carbohydrate diet in the mice.
EPC plays a role in new blood vessel growth, and corresponding to the decrease seen with EPC, low-carbohydrate fed mice were unable to respond to ischemia (oxygen deprivation).10,13 One of the factors known to stimulate EPC growth (pAkt) is a ‘downstream’ molecule in the insulin-signaling cascade. ‘Downstream’ means insulin turns on one molecule, which turns on another, which turns on pAkt. Statin drugs (Lipitor, for example), exercise, and estrogen have been shown to counteract impaired EPC production.13 Low-carbohydrate fed mice had significantly lowered insulin concentrations compared to other diets, as would be expected. Type 2 diabetics who are insulin-resistant also demonstrated impaired EPC production.14 Though this is not the entire reason EPC growth is impaired in low-carbohydrate diets, it likely plays a role.
Thus far, low-carbohydrate diets have been shown to markedly increase atherosclerosis, even compared to high-fat diets. This is in a setting that would not raise suspicion. In fact, many measures suggest that cardiovascular health is improved with low-carbohydrate dieting. Also, the ability of the circulatory system (blood vessels) to respond to oxygen deprivation is seriously impaired.
This study did not look at ketogenic dieting, as the carbohydrate content was high enough to prevent ketosis. Thus, it is difficult to determine whether the same concerns would be present during ketogenic dieting. However, another concerning observation has been noted during ketogenic dieting that adds another level of risk.
One study published last year showed that people on a ketogenic diet had impaired dilation, whereas those on a low-fat diet actually demonstrated improved flow-mediated dilation and response to a dilating drug. Similar impairment is again seen in people with insulin resistance.15,16 This adverse effect may be exaggerated when saturated fat is high, but the balance of research appears to suggest that if mono- and polyunsaturated fats are consumed in sufficient quantities and saturated fats are moderated, blood vessels should respond more appropriately to dilating signals.17 Research looking at non-ketogenic, low-carbohydrate diets do not demonstrate the same defect, suggesting there may be different risks present during ketosis.18-20
Given the findings in this study, it is impossible to recommend low-carbohydrate or ketogenic diets to those with a significant personal or family history of cardiovascular disease. In fact, this data supports the recommendation for moderate carbohydrate intake sufficient to maintain a baseline insulin presence. The exact recommendation for carbohydrates remains fuzzy at this time, but it appears that at least 60-100 grams per day of low-glycemic carbohydrates, along with an intake of mono- and polyunsaturated fats to counterbalance saturated fat intake, is the optimal diet plan. Excessive carbohydrate intake should be avoided as well, suggesting that the age-old adage of moderation in all things remains sound advice.
