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http://www.blogalegentcreighton.com/index.php/2010/what-is-normal/ (What is Normal? | BlogAlegentCreighton | Alegent Creighton Health Heart)
Dr. Frederick Frankenstein: [to Igor] Now that brain that you gave me. Was it Hans Delbruck’s?
Igor: [pause, then] No.
Dr. Frederick Frankenstein: Ah! Very good. Would you mind telling me whose brain I DID put in?
Igor: Then you won’t be angry?
Dr. Frederick Frankenstein: I will NOT be angry.
Igor: Abby Someone.
Dr. Frederick Frankenstein: [pause, then] Abby Someone. Abby who?
Igor: Abby Normal.
Dr. Frederick Frankenstein: [pause, then] Abby Normal?
Igor: I’m almost sure that was the name.
In medical school I learned how laboratory “normals” are set. These are the numbers that represent the range where presumably normal patients fall. For example, if you get your hemoglobin measured in one of our Alegent labs you’ll be provided with your result accompanied by a range of normals (13.5 – 17.5 gm/dl). If you have a hemoglobin level of 13.5, you’re normal; if it’s 13.4, you’re not (and are thus mildly anemic).
To determine the reference range for any laboratory value you first need a few thousand presumably healthy volunteers. You draw blood from all of them and measure whatever you’re looking for—as an example let’s use a made-up blood component we want to assess, say “midi-chlorians”. You find that your healthy subjects have a wide variety of midi-chlorian levels, some high, some low, most of them right in the middle. Now comes the magic of statistics. You figure out what level of midi-chlorians the bottom and top 2.5% of subjects have. Then you simply take the middle 95% of values and label them normal, and those at the highest and lowest levels become the abnormals. If the reference range for midi-chlorians is 4.5 to 178.9 mJjb (millijarjars)—implying that 95% of the normal population fall into this span—then someone with a level of 180 mJjb would be defined as abnormal, even if the specimen came from one of your normal volunteers.
And, as everyone knows, one’s midi-chlorian level is fixed from birth. What about bodily components that change over time? The b-type natiuretic peptide (BNP), for example, is a protein marker of congestive heart failure that rises steadily with age and varies according to gender and level of obesity. A “normal” BNP for you at age twenty (when you can still fit into those skinny jeans) may not be the same when you are twice that age (and maybe twice that size), even if you consider yourself to still be normal.
Another issue relates to tests where there is debate about what should be considered normal. The best example in this category is LDL cholesterol (LDL-C). Pull in a thousand random healthy volunteers from the U.S. and you’ll find that the average LDL-C is around 130 mg/dL. Does that mean that 130 mg/dL should be the standard for what is normal? What if our supposedly “healthy” volunteers aren’t so healthy after all? Just because the average LDL-C in this country is 130 mg/dL doesn’t necessarily mean that this represents the level at which our bodies function most normally.
Lipid researchers have long postulated that the LDL-C levels in our society are anything but normal. We’ve long known that LDL-C rises with age in our society despite the fact that this is actually not a normal phenomenon. Consider this paragraph from a review entitled “Redefining Normal Low-Density Lipoprotein Cholesterol” in a recent edition of Journal of American College of Cardiology:
“At least two adult human populations, however, do not exhibit this progressive increase in LDL-C with age. One population consists of hunter-gatherer societies, diverse in geographic location and ethnic origin but arguably living the way humans did 10,000 years ago. LDL-C levels remain in the 35 to 70 mg/dL range. In modern societies, rural Chinese blood levels often fall within this range. In neonates and these two adult groups, atherosclerotic coronary disease is rare. The consistency of these diverse human data sources, taken together with the mammalian species data, supports the speculation that the putative normal range of LDL-C in adult humans may be approximately 35 to 70 mg/dL.”
Sure, 130 mg/dL of LDL-C is typical in our population, but what would it be if we didn’t spend 90% of our lives subsisting on fast food and exercising as much as catatonic tree sloths? In the case of LDL-C, normal is likely less than 70 mg/dL and anything much above that (in other words, nearly all of us) falls in the abnormal range.
http://www.blogalegentcreighton.com/index.php/2012/optimal-cholesterol-level/ (Optimal Cholesterol Level | BlogAlegentCreighton | Alegent Creighton Health Heart)
But is the average American—whose mean cholesterol level is 208 mg/dL, by the way—the same things as the average healthy American? Dr. James H. O’Keefe of the Mid America Heart Institute in Kansas City, MO, and an expert on lipids, argues that we humans are designed to thrive on cholesterol levels far below 208 mg/dL. In an essay published in the Journal of the American College of Cardiologyin 2004, Dr. O’Keefe suggests that we need to look to hunter-gatherer societies and our mammalian cousins to discover what the truly optimal lipid panel should look like.
http://content.onlinejacc.org/article.aspx?articleid=1135650&issueno=11
The Kalihari tribe in Africa, to bring up one example, subsists on a diet high in complex carbohydrates and lean proteins but very little fat. The average cholesterol level in those individuals is well under 150 mg/dL and, not coincidentally, the incidence of coronary atherosclerosis is correspondingly very low. Across the board, “less civilized” societies whose diet and lifestyle mimic early human experience (ie. the diet that our bodies evolved to thrive on) tend to have a combination of very low cholesterol level and extreme longevity. Even babies, who enter this world with an average LDL cholesterol of 30-70 mg/dL, give us some insight into what our normal level should be.
Mammals who share most of our DNA, such as primates, also do best with less cholesterol in their system. In fact (writes Dr. O’Keefe), “modern humans are the only adult mammals, excluding some domesticated animals, with a mean LDL level over 80 mg/dL and a total cholesterol over 160 mg/dL.”
JAMA Network | JAMA Internal Medicine | Lipid Values in Kalahari Bushmen
Samples of the plasma from nine male adult bushmen were analyzed for their lipid content. The mean results obtained (total cholesterol = 77 mg/100 ml, phospholipids = 107 mg/100 ml, and triglycerides= 49 mg/100 ml) were extremely low. The probable reasons for this finding are the very low dietary fat content and habitually high physical activity of Kalahari bushmen.
Dr. Frederick Frankenstein: [to Igor] Now that brain that you gave me. Was it Hans Delbruck’s?
Igor: [pause, then] No.
Dr. Frederick Frankenstein: Ah! Very good. Would you mind telling me whose brain I DID put in?
Igor: Then you won’t be angry?
Dr. Frederick Frankenstein: I will NOT be angry.
Igor: Abby Someone.
Dr. Frederick Frankenstein: [pause, then] Abby Someone. Abby who?
Igor: Abby Normal.
Dr. Frederick Frankenstein: [pause, then] Abby Normal?
Igor: I’m almost sure that was the name.
In medical school I learned how laboratory “normals” are set. These are the numbers that represent the range where presumably normal patients fall. For example, if you get your hemoglobin measured in one of our Alegent labs you’ll be provided with your result accompanied by a range of normals (13.5 – 17.5 gm/dl). If you have a hemoglobin level of 13.5, you’re normal; if it’s 13.4, you’re not (and are thus mildly anemic).
To determine the reference range for any laboratory value you first need a few thousand presumably healthy volunteers. You draw blood from all of them and measure whatever you’re looking for—as an example let’s use a made-up blood component we want to assess, say “midi-chlorians”. You find that your healthy subjects have a wide variety of midi-chlorian levels, some high, some low, most of them right in the middle. Now comes the magic of statistics. You figure out what level of midi-chlorians the bottom and top 2.5% of subjects have. Then you simply take the middle 95% of values and label them normal, and those at the highest and lowest levels become the abnormals. If the reference range for midi-chlorians is 4.5 to 178.9 mJjb (millijarjars)—implying that 95% of the normal population fall into this span—then someone with a level of 180 mJjb would be defined as abnormal, even if the specimen came from one of your normal volunteers.
And, as everyone knows, one’s midi-chlorian level is fixed from birth. What about bodily components that change over time? The b-type natiuretic peptide (BNP), for example, is a protein marker of congestive heart failure that rises steadily with age and varies according to gender and level of obesity. A “normal” BNP for you at age twenty (when you can still fit into those skinny jeans) may not be the same when you are twice that age (and maybe twice that size), even if you consider yourself to still be normal.
Another issue relates to tests where there is debate about what should be considered normal. The best example in this category is LDL cholesterol (LDL-C). Pull in a thousand random healthy volunteers from the U.S. and you’ll find that the average LDL-C is around 130 mg/dL. Does that mean that 130 mg/dL should be the standard for what is normal? What if our supposedly “healthy” volunteers aren’t so healthy after all? Just because the average LDL-C in this country is 130 mg/dL doesn’t necessarily mean that this represents the level at which our bodies function most normally.
Lipid researchers have long postulated that the LDL-C levels in our society are anything but normal. We’ve long known that LDL-C rises with age in our society despite the fact that this is actually not a normal phenomenon. Consider this paragraph from a review entitled “Redefining Normal Low-Density Lipoprotein Cholesterol” in a recent edition of Journal of American College of Cardiology:
“At least two adult human populations, however, do not exhibit this progressive increase in LDL-C with age. One population consists of hunter-gatherer societies, diverse in geographic location and ethnic origin but arguably living the way humans did 10,000 years ago. LDL-C levels remain in the 35 to 70 mg/dL range. In modern societies, rural Chinese blood levels often fall within this range. In neonates and these two adult groups, atherosclerotic coronary disease is rare. The consistency of these diverse human data sources, taken together with the mammalian species data, supports the speculation that the putative normal range of LDL-C in adult humans may be approximately 35 to 70 mg/dL.”
Sure, 130 mg/dL of LDL-C is typical in our population, but what would it be if we didn’t spend 90% of our lives subsisting on fast food and exercising as much as catatonic tree sloths? In the case of LDL-C, normal is likely less than 70 mg/dL and anything much above that (in other words, nearly all of us) falls in the abnormal range.
http://www.blogalegentcreighton.com/index.php/2012/optimal-cholesterol-level/ (Optimal Cholesterol Level | BlogAlegentCreighton | Alegent Creighton Health Heart)
But is the average American—whose mean cholesterol level is 208 mg/dL, by the way—the same things as the average healthy American? Dr. James H. O’Keefe of the Mid America Heart Institute in Kansas City, MO, and an expert on lipids, argues that we humans are designed to thrive on cholesterol levels far below 208 mg/dL. In an essay published in the Journal of the American College of Cardiologyin 2004, Dr. O’Keefe suggests that we need to look to hunter-gatherer societies and our mammalian cousins to discover what the truly optimal lipid panel should look like.
http://content.onlinejacc.org/article.aspx?articleid=1135650&issueno=11
The Kalihari tribe in Africa, to bring up one example, subsists on a diet high in complex carbohydrates and lean proteins but very little fat. The average cholesterol level in those individuals is well under 150 mg/dL and, not coincidentally, the incidence of coronary atherosclerosis is correspondingly very low. Across the board, “less civilized” societies whose diet and lifestyle mimic early human experience (ie. the diet that our bodies evolved to thrive on) tend to have a combination of very low cholesterol level and extreme longevity. Even babies, who enter this world with an average LDL cholesterol of 30-70 mg/dL, give us some insight into what our normal level should be.
Mammals who share most of our DNA, such as primates, also do best with less cholesterol in their system. In fact (writes Dr. O’Keefe), “modern humans are the only adult mammals, excluding some domesticated animals, with a mean LDL level over 80 mg/dL and a total cholesterol over 160 mg/dL.”
JAMA Network | JAMA Internal Medicine | Lipid Values in Kalahari Bushmen
Samples of the plasma from nine male adult bushmen were analyzed for their lipid content. The mean results obtained (total cholesterol = 77 mg/100 ml, phospholipids = 107 mg/100 ml, and triglycerides= 49 mg/100 ml) were extremely low. The probable reasons for this finding are the very low dietary fat content and habitually high physical activity of Kalahari bushmen.
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