Watch as we discuss the important markers of heart disease and vascular disease risk. We will talk about how these markers can help you understand what your body is doing in the process of making or reversing atherosclerosis (plaque in the vessels). And, should you really be taking that STATIN (cholesterol lowering) drug? Get the scoop here as Dr. Nally very simply points out how the right diet can and will lower your cholesterol without the use of medications.
Research in the last 10 years points to the small-dense LDL particle as the atherogenic component of cholesterol (Hoogeveen RC et al., Arterioscler Thoromb Vasc Biol, 2014 May; Ivanova EA et al., Oxidative Med Cell Longevity, 2017 Apr). Studies in the last five years have identified that elevated small-dense LDL cholesterol correlates much more closely with risk for inflammation, heart disease and vascular disease (Williams PT, et al. Atherosclerosis. 2014 April; 233(2): 713-720.)
Recent research in the last three years demonstrates that small dense LDL cholesterol is a better marker for prediction of cardiovascular disease than total LDL-C (Hoogeveen RC et al., Arterioscler Thromb Vasc Biol. May 2014, 34(5): 1069-1077l; Ivanova EA et al., Oxidative Med Cell Longev. 2017).
Additionally, higher LDL-C is actually predictive of longer life and has been demonstrated to correlate with longevity (Ravnskov U et al., BMJ Open, 2016 Jun 12;6(6): e010401). And, a low LDL-C actually increases risk of early mortality (Schwartz I et al., Lancet 2001, 358: 351-55).
It is commonly understood that LDL-C will rise with increased saturated fat intake on a ketogenic diet. This has been know and reported in the scientific literature for over twenty years. This is to be expected, because LDL-C is really a measurement of three different LDL sub-particles (“big fluffy, medium, and small dense”). Increased saturated fat intake, while at the same time lowering carbohydrate intake, actually causes a shift in these low density particles to a bigger “fluffier” particle conformation (Griffin BA et al., Clin Sci (Lond), 1999 Sep).
The 2015 British Medical Journal, referenced above, analyzed the relevant 19 peer reviewed medical articles that included over 68,000 participants. This review showed that there is no association of high LDL-C with mortality (meaning that an elevated LDL-C does not lead to an increased risk of death from heart or vascular disease). I realize that, in stark opposition to the landmark review above, The American Heart Association’s Presidential Advisory published their position in the June 20, 2017 issue of Circulation. They stated that saturated fat is the cause of increased LDL-C and they further extrapolated that elevated LDL-C is associated with an increase in death by cardiovascular disease. This boldfaced claim is only based on one single small four year (2009-2013) literature review completed by the World Health Organization with a total of only 2353 participants, most of these studies only lasting 3-5 weeks (not nearly long enough to see fully effective cholesterol changes) and none of which had any focus on carbohydrate intake, insulin levels or LDL sub-particle measurement (Mensink RP, Geneva: WHO Library Cataloguing-in-Publication Data, 2016).
Based upon the most current scientific evidence above and my clinical experience, the large body of evidence above demonstrates the use of total cholesterol and LDL-C to determine vascular disease risk to be ineffective tools. A low carbohydrate/ketogenic diet lowers small dense LDL cholesterol, triglycerides and blood sugar and in many cases, the use of cholesterol drug (STATIN) therapy is not needed and ineffective in comparison with a ketogenic/carbohydrate restricted lifestyle.
Watch as Dr. Nally discusses how eating more fat actually lowers your cholesterol and your risk for heart disease. Is a ketogenic lifestyle more effective than cholesterol medication? Find out as we discuss this an many fascinating cholesterol questions from Dr. Nally’s Periscope watchers from around the world. He also answers questions about his KetoEssentials Multi-Vitamin, Exogenous Ketones, and Pork Rinds (his favorite are the Pork Clouds brand).
So, mix up a bowel of fluff and grab a spoon while you listen and lower your cholesterol.
On this evenings PeriScope video we talked about cholesterol. And, and you can see an updated, in depth discussion about cholesterol on my YouTube channel here. Please go check it out and if you find it helpful, please follow me here and on YouTube. The is the burning question on everyone’s mind who starts a Low-Carb, High Fat or Ketogenic Diet: “What will happen to my cholesterol if I lower my carbohydrates and eat more fat?”
The answer . . . it will improve!
How do I know this? I’m an obesity specialist. I specialize in FAT or lipids (to put it kinder scientific terms). To specialize in fat, one must know where it came from, what it’s made of and where it is going. And, this has been the case with every single patient I have used this dietary change with for the last ten years, myself included.
Lets start with the contents of the standard cholesterol or “Lipid Panel”:
Total Cholesterol
HDL-C (the calculated number for “good” cholesterol)
LDL-C (the calculated number for “bad” cholesterol).
Triglycerides
The first problem with this panel is that it makes you believe that there are four different forms of cholesterol. NOT TRUE! Actually cholesterol is cholesterol, but it comes in different sizes based on what it’s function is at that moment in time. Think of cholesterol as a bus. There are bigger busses and smaller busses. Second, triglyceride is actually the passenger inside the HDL and the LDL busses. And third, Total Cholesterol is the sum of the HDL, LDL, as well as ILDL & VLDL which aren’t reported in the “Lipid Panel” above.
The fourth thing that this panel doesn’t tell you is that HDL & LDL are actually made up of sub-types or sub-particles and are further differentiated by weight and size.
For our conversation, we need to know that the number of LDL particles (LDL-P) can actually be measured in four different ways and these measurements have identifed that there are three sub-types: “Big fluffy” large dense LDL, medium dense LDL, and small-dense LDL. Research has identified that increased numbers of small-dense LDL correlates closely with risk for inflammation, heart disease and vascular disease (1).
If you’ve been a follower of my blog for a while, you’ve seen this picture before. This picture illustrates why an LDL-C (the bad cholesterol measurement) can be misleading. Both sides of the scale reflect an LDL-C of 130 mg./dl. However, the LEFT side is made up of only a few large fluffy LDL particles (this is the person with reduced risk for heart disease) called Pattern A or a LDL healthy cholesterol level. Even though the LDL-C is elevate above the recommended level of 100 mg/dl, the patient on the left has much less risk for vascular disease (this is why you CAN’T trust LDL-C as a risk factor).
The RIGHT side of the scale shows that the same 130 mg/dl of LDL-C is made up of man more small dense LDL particles (called “sd LDL-P”) with a Pattern B type that is as increased risk for heart or vascular disease. This is where the standard Lipid Panel above, fails to identify heart disease and it’s progression.
Research tells us that the small dense LDL particle levels increase as the triglycerides increase. And we know that Triglyceride levels increase in the presence of higher levels of insulin leading to a cascade of inflammatory changes. Insulin is directly increased by the ingestion of simple and complex carbohydrates. Insulin also increases with the ingestion of too much protein. So, that chicken salad or the oatmeal you ate, thinking it was good for you, actually just raised your cholesterol. If you are insulin resistant, your cholesterol just increased by 2-10 times the normal level (see my article here on how insulin resistance causes this.)
“Ok, but Dr. Nally, there are four different companies out in the market measuring these fractional forms of cholesterol. Which one should I choose?”
There are actually five different ways you can check your risk.
Apolipoprotein levels. This can be done through most labs; however, this test doesn’t give you additional information on insulin resistance that the other tests can.
Berkley Heart Lab’s Gradient Gel Electrophoresis – This test gives a differentiation based on particle estimation between Pattern A and Pattern B
Vertical Auto Profile (VAP-II) test by Arthrotec – This test determines predominant LDL size but does not give a quantifiable lipoprotein particle number which I find very useful in monitoring progression of insulin resistance and inflammation.
NMR Spectroscopy from LipoScience – This test measures actual lipoprotein particle number as well as insulin resistance scores and will add the Lp(a) if requested. I find the NMR to be the most user friendly test and useful clinically in monitoring cholesterol, vascular risk, insulin resistance progression and control of the inflammation caused by diabetes. This test has the least variation based on collection methods if frozen storage is used.
Ion-Mobility from Quest – This test also measures lipoprotein particle number but does not include insulin resistance risk or scoring. Because the test is done through a gas-phase electric differential, the reference ranges for normal are slightly different from the NMR.
In regards to screening for cardiovascular risk, the use of all five approaches are more effective than the standard lipid panel. However, I have found that clinically the NMR Lipo-profile or the Cardio I-Q Ion-Mobility tests are the most useful in additionally monitoring insulin resistance, inflammation, and disease progression.
It is was the use of these tests that demonstrated to me the profound effect of carbohydrate restriction and ketogenic lifestyles on vascular and metabolic risk. We talk more about these tests on my YouTube video .
Hope this helps.
References:
Williams PT, et al. Comparison of four methods of analysis of lipoprotein particle subfractions for their association with angiographic progression of coronary artery disease. Atherosclerosis. 2014 April; 233(2): 713-720.
I can’t help myself. Some days I enjoy a good murder mystery, but on others, I enjoy a good journal article elucidating our understanding of leptin. No, leptin is not a tiny Irish folk character or even a superhero. Leptin is a hormone. It’s made by fat cells. Anything made by fat cells becomes fascinating to a “fat doctor.”
Why is learning about leptin illuminating?
Well, if Sir Arthur Conan Doyle was an Obesity Specialist, the mystery would have been that Mr. Plump was killed by the wrench in the kitchen, but the wrench seems to have never left tool case in the garage. No one has been able to figure out how leptin, the allegorical wrench, plays its roll in lepin resistance. We know that a lack of leptin allows hunger to persist and a person without leptin will continue to eat without the sensation of feeling full – leading to obesity. What we haven’t understood is – what causes the brain to no longer sense larger and larger amounts of leptin being produced by those who are obese.
That is . . . we haven’t understood it until now. . .
We have known for some time that the hormone leptin is a key hormone produced by the adipose (fat) cells that suppresses hunger. A majority of obese patients in my clinic have elevated circulating leptin levels 2-10 times the normal levels. We know that a lack of leptin leads to obesity, but the patients that I see in the office are producing an over abundance consistent with leptin resistance. The leptin signal is not being recognized by the brain. This is very similar to type II diabetes and insulin resistance. The pancreas is producing an over abundance of insulin, but the cells are recognizing the signal to let the glucose in through the door way.
Three recent and very interesting studies have pointed to the probable cause. First, one of the most common genetic disorders causing human obesity is loss of function of the melanocortin receptor.
Image adapted from 2011 “The Skinny About Fat” presentation – Adam Nally, D.O.
If the MC-4R receptor is broken, suppression of appetite is limited, continued eating occurs and weight gain continues. Leptin, produced by every adipose cell in the body, is carried in the blood stream to the brain and must pass through the blood-brain barrier. Once it crosses the blood-brain barrier and enters the hypothalamus, it has a stimulatory effect on the MC-3R receptor in the Arcuate Nucleus of the hypothalamus causing stimulation of the MC-4R receptor in the Parventricular Nucleus and Lateral Hypothalamus to turn off hunger.
Image adapted from 2011 “The Skinny About Fat” presentation – Adam Nally, D.O.
However, if leptin cannot cross the blood brain barrier, the signal is never received from the adipose cells and continued eating without satiation (feeling full) persists. Studies have shown that dietary fructose ingestion alone or in combination with diets high in fat suppress the transmission of leptin across the blood-brain barrier.
Image adapted from 2011 “The Skinny About Fat” presentation – Adam Nally, D.O.
Fructose is the primary component of high-fructose corn syrup, and makes up 45-50% of every other type of natural form of sugar (sucrose). Yes, it’s the major component found in table sugar, brown sugar, honey, agave, molasses and maple syrup. This is why a Paleolithic Diet isn’t fully effective for people with leptin resistance.
Lastly, anything that raises triglycerides inhibits leptin from crossing the blood-brain barrier.
Image adapted from 2011 “The Skinny About Fat” presentation – Adam Nally, D.O.
Insulin has a direct effect on triglycerides. (See the articles “Insulin Resistance & The Horse,” “Fat Thoughts on Cholesterol,” “Ketogenic Living” and “So, What is this Ketogenic Thing?“). If your insulin levels go up, triglyceride production goes up. The patient with insulin resistance, pre-diabetes, impaired fasting glucose or type II diabetes produces between two to ten times the normal amount of insulin when eating the standard American diet (SAD diet). These patients have significant triglyceride elevation because of the high insulin response to carbohydrates in their diet. (Many of them were told by their doctor that “It’s just genetic so take your Lipitor.”) Statin drugs lower the LDL-C (calculated “bad cholesterol” level), but don’t reduce triglycerides effectively. Inadequate treatment of high triglycerides allows poor blood-brain barrier transmission of leptin and worsening leptin resistance.
In fact, this is the challenge and problem with the “frequent fasting” or “intermittent fasting” fad for weight loss that has been popping up in the blogosphere. If fasting reaches a state of starvation (which is a very fine line metabolically), it stimulates a stress response . . . causing a spike in cortisol, release of glycogen (a form of sugar), a compensatory release of insulin and a spike in triglycerides. If you have tried intermittent fasting and you’ve gained weight, you are probably not “fasting,” your probably “starving.” We’ve known for years that triglycerides are elevated in starvation. This diminishes leptin’s ability to cross the blood-brain barrier and leads to worsening leptin and insulin resistance.
High leptin levels caused by leptin resistance also seems to play a significant role in the development of diabetic retinopathy – damage to the tiny blood vessels at the back of the eye feeding the retina. Diabetic retinopathy starts insidiously without any symptoms initially and can lead to eventual blindness if not treated. Leptin seems to upregulate vascular endothelial growth factor (VEGF) which leads to narrowing of the blood vessels called “ischemia.” Chronic ischemia of the retinal vessels leads to damage to the delicate retinal cells of the eye.
So what do you do if you have leptin resistance. First, eliminate carbohydrates from your diet, especially sugars, high fructose corn syrup and any other form of simple sugar. This is why I am such a big fan of low carbohydrate, high fat diets.
Third, use a supplement containing alpha-lipoic acid, carnosine high gamma vitamin E and benfothiamin (derivative of Vitamin B1). These have been demonstrated to decrease inflammation and render protection to the blood vessels.
The use of Epigallocatechin gallate (EGCg), a derivative extract of green tea, has been shown to repress hepatic glucose production, one of the insidious factors of insulin resistance, and may play a role in stabilizing the effect insulin has on production of triglycerides. You should consider using KetoEssentials. It is my specially formulated multivitamin that contains all of the above supplements, and includes methylated folic acid (B9), the necessary vitamin B6 & B12, chromium, vandium & zinc that help to further stabilize insulin resistance.
Fourth, get a good night’s sleep. Lack of sleep causes a stress response, increases cortisol, raises blood sugar and insulin leading to further leptin resistance.
Fifth, mild to moderate resistance exercise has been shown for years to improve insulin resistance significantly. If you’re not exercising, take a 20 minute walk 2-3 times per week, ride a bike for 20 minutes, start a weight lifting program, consider yoga or Pilates, Remember, jumping to conclusions, flying off the handle, carrying things too far, dodging responsibility and pushing your luck don’t qualify as resistance exercise.
Above all, if you’re having trouble losing weight, controlling insulin or leptin, see your doctor. He or she can really help.
References:
Ray F. Gariano, Anjali K. Nath, Donald J. D’Amico, Thomas Lee, and M. Rocio Sierra–Honigmann. “Elevation of Vitreous Leptin in Diabetic Retinopathy and Retinal Detachment.” Invest Ophthalmol Vis Sci. 2000;41:3576–3581
Hammes HP, Du X . “Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy.” Nat Med. 2003 Mar;9(3):294-9. Epub 2003 Feb 18.
Hipkiss AR, Brownson . “Reaction of carnosine with aged proteins: another protective process?” Ann N Y Acad Sci. 2002 Apr;959:285-94.
Zachary A. Knight, K. Schot Hannan, Matthew L. Greenberg, Jeffrey M. Friedman. “Hyperleptinemia Is Required for the Development of Leptin Resistance.” PLoS ONE 5(6): e11376. doi:10.1371/journal.pone.0011376.
Min-Diane Li. “Leptin and Beyond: An Odyssey to the Central Control of Body Weight.” The Yale Journal of Biology and Medicine. 2011;84(1):1-7.
Eri Suganami, Hitoshi Takagi,Hirokazu Ohashi, Kiyoshi Suzuma, Izumi Suzuma, Hideyasu Oh, Daisuke Watanabe, Tomonari Ojimi, Takayoshi Suganami, Yasushi Fujio, Kazuwa Nakao, Yoshihiro Ogawa and Nagahisa Yoshimura. “Leptin Stimulates Ischemia-Induced Retinal Neovascularization: Possible Role of Vascular Endothelial Growth Factor Expressed in Retinal Endothelial Cells.” Diabetes. September, 2004. vol. 53 no. 9 2443-2448
Joseph R. Vasselli, Philip J. Scarpace, Ruth B. S. Harris, and William A. Banks. “Dietary Components in the Development of Leptin Resistance.” Adv. Nutr. 2013: 4: 164–175.
Joseph R. Vasselli. “Fructose-induced leptin resistance: discovery of an unsuspected form of the phenomenon and its significance.” Am J Physiol Regul Integr Comp Physiol. 2008 Nov;295(5):R1365-9. doi: 10.1152/ajpregu.90674.2008. Epub 2008 Sep 10.
Waltner-Law ME, Wang XL Epigallocatechin gallate, a constituent of green tea, represses hepatic glucose production. J Biol Chem. 2002 Sep 20;277(38):34933-40. Epub 2002 Jul 12.
85% of the people that walk through my office doors have some degree of insulin resistance.
What is “insulin resistance?” It is an over production of insulin in response to ANY form of carbohydrate intake (yes, even the “good carbs” cause an insulin over-response in a person with insulin resistance.)
How do I know this? Because I routinely check insulin levels (I check them every three months) and the down stream markers of insulin on a large number of the patients that I see. I have been fascinated by the fact that a diet high in both sugar and fat [like the Standard American Diet, (SAD) diet] turn on the genetics leading to insulin resistance. Starch and sugar load the genetic gun.
Insulin acts like a key at the glucose doorway of every cell in your body. In many people, the insulin signal is blocked by hormones produced in the fat cell and the the insulin, acting like a “dull or worn out key” – can’t open the glucose doorway as efficiently.
So, the body panics, and releases extra insulin in response to the same load of carbohydrate or glucose. People with insulin resistance will produce between 2-20 times the normal amount of insulin in response to a simple carbohydrate load. Recent studies(1, 2) reveal high cholesterol and diets high in both fat and carbohydrate cause insulin resistance to progress or worsen.
So, instead of producing enough insulin to accommodate the one slice of bread or the one apple that you might eat, the insulin resistant person produces enough insulin for an entire loaf of bread or an entire bushel of apples. This excess insulin then stimulates one or all of the following:
Weight Gain – Insulin directly stimulates weight gain by activating lipoprotein lipase to take up triglycerides into the fat cells. This causes direct storage of fat and increases your waistline. (3)
Elevated Triglycerides – Insulin directly stimulates production of free fatty acids and triglycerides through hepatic gluconeogenesis and is even more notably amplified by the broken signaling mechanism of the FOX-01 phosphorylation mechanism in patients with insulin resistance. (4)
Increased number of Small Dense LDL (sdLDL) particles – Low density lipoprotein (LDL, or “bad cholesterol”) is actually comprised of various sized lipoproteins including small, medium and large. As triglycerides increase, the small dense LDL particle numbers increase. Research points to the fact that it is the small dense particle that is highly atherogenic (leading to the formation of vascular plaques within the arteries). (5, 8)
Elevated Uric Acid – Leptin resistance and insulin resistance syndromes are often found together and are suspected to have significant influence on each other. High insulin loads lead to “sick adipose cells” causing leptin resistance. This has a dramatic effect on hepatic fructose metabolism increasing the production of uric acid. Excess insulin suppresses urinary excretion of uric acid and dramatically increases serum content of uric acid and the risk of kidney stones and gout. (6, 7)
Increased Inflammation – Increased levels of circulating insulin have a direct correlation on raising many of the inflammatory markers and hormones including TNF-alpha and IL-6 in the body (9). Any disease process that is caused by chronic inflammation can be amplified by increased circulating levels of insulin including asthma, acne, eczema, psoriasis, arthritis, inflammatory bowel and celiac disease, etc.
Elevated Blood Pressure – Increased uric acid production from insulin resistance as noted above directly suppresses production of nitric oxide within the vasculature and increases blood pressure (7). This completes the triad of metabolic syndrome (elevated triglycerides & cholesterol, weight gain, and elevated blood pressure) found in patients with insulin resistance.
Water Retention – We have known for many years that insulin affects the way the kidney uses sodium in the distal nephron. Insulin has a direct effect on sodium retention in the kidney. As insulin levels rise, the kidney retains increased levels of sodium (10). Water follows sodium and thereby causes fluid retention. This is the reason that many of my insulin resistant patients who have struggled with leg swelling and edema suddenly improve when they correct their diet and their high circulating insulin levels fall. It is also the reason that many of my patients show up in my office after the holidays with swollen legs and amplified swelling in their varicose veins after cheating on their ketogenic diets.
If you are plagued by any or all of these, my first suggestion is to see your doctor and get screened for insulin resistance. I treat patients with these every day and have reversed these effects in thousands of patients with the correct diet and/or medications. Having seen these signs and patterns over the last 20 years of medical practice, I am still astonished every day by the dramatic effect our diet plays on the hormonal changes within the body. Remember that the food you eat is actually the most powerful form of medicine . . . and the slowest form of pernicious poison.
Cholesterol Elevation Impairs Glucose-Stimulated Ca2+Signaling in Mouse Pancreatic β-Cells, Endocrinology, June 2011, Andy K. Lee, Valerie Yeung-Yam-Wah, Frederick W. Tse, and Amy Tse; DOI: http://dx.doi.org/10.1210/en.2011-0124
Glucose-Stimulated Upregulation of GLUT2 Gene Is Mediated by Sterol Response Element–Binding Protein-1c in the Hepatocytes, DIABETES, VOL. 54, JUNE 2005; Seung-Soon Im, Seung-Youn Kang, So-Youn Kim, Ha-il Kim, Jae-Woo Kim, Kyung-Sup Kim and Yong-Ho Ahn
Selective versus Total Insulin Resistance: A Pathogenic Paradox, Cell Metabolism, Volume 7, Issue 2, 6 February 2008, Pages 95–96, Michael S. Brown, Joseph L. Goldstein
Association between small dense LDL and early atherosclerosis in a sample of menopausal women, Department of Clinical Medicine and Surgery, University “Federico II” Medical School, Naples, Italy Division of Cardiology, Moscati Hospital, Aversa, Italy A. Cardarelli Hospital, Naples, Italy, Gentile M, Panico S, et al., Clinica Chimica Acta, 2013
Sugar, Uric Acid and the Etiology of Diabetes and Obesity. Diabetes. 2013;62(10):3307-3315, Richard J. Johnson; Takahiko Nakagawa; L. Gabriela Sanchez-Lozada; Mohamed Shafiu; Shikha Sundaram; Myphuong Le; Takuji Ishimoto; Yuri Y. Sautin; Miguel A. Lanaspa
Fructose: metabolic, hedonic, and societal parallels with ethanol. J Am Diet Assoc. 2010 Sep;110(9):1307-21. doi: 10.1016/j.jada.2010.06.008. Lustig RH
Cardiovascular Risk in Patients Achieving Low-Density Lipoprotein Cholesterol and Particle Targets. Atherosclerosis. Vol 235; 585-591, May 2014, Peter P. Toth, Michael Grabner, Rajeshwari S. Punekar, Ralph A. QuimboMark J. Cziraky c, Terry A. Jacobson
Chronic Subclinical Inflammation as Part of the Insulin Resistance Syndrome The Insulin Resistance Atherosclerosis Study (IRAS), Circulation, July 2000, 102:42-47; Andreas Festa, MD; Ralph D’Agostino, Jr, PhD; George Howard, DrPH; Leena Mykka¨nen, MD, PhD; Russell P. Tracy, PhD; Steven M. Haffner, MD
The Effect of Insulin on Renal Sodium Metabolism. Diabetologia. September 1981, Volume 21, Issue 3, pp 165-171. R. A. DeFronzo
