The Problematic Paradigm of LCL-C, Part 12

Part 12 - The Effects of Diet on LDL-C, As Told By Energy Delivery

Previous - Part 11 - The Effects of Diet on Markers of Cardiovascular and Metabolic Health

In the previous, penultimate section we touched on the ways in which macronutrient distribution affects common markers of cardiometabolic health. One incredibly popular marker still remains, though, and that is of course LDL-C.

There are a couple good reasons to save LDL-C for last. For one, it doesn’t move in a consistent direction with carbohydrate restriction in the way HDL-C, triglycerides, or blood sugar might – how it moves depends on who is restricting carbohydrates. But mostly, we’re discussing it last because this entire series focuses on the shortcomings of the modern cholesterol paradigm, in which LDL-C is the central player.

To be clear, I am not making the claim that nothing in the world aside from energy delivery affects LDL-C levels. For example, plant sterols (essentially the plant version of cholesterol, but not usable in the human body) lower LDL-C to a certain degree. But, as has been explained at length in this series, I am making the claim that energy delivery is the primary driver of LDL cholesterol levels. And furthermore, that this energy system is driven primarily by what you eat.

So…what happens to your LDL-C when you eat more carbs, or, perhaps, what happens when you eat less?

 

Personal Anecdote

Early last month I consumed a fairly prodigious amount of cheese (and more – the reasons why are here, but aren’t important) over the course of a weekend before having my blood drawn the next day. My LDL-C on that morning? 108mg/dl. This was on the heels of some significant fat consumption – a three day average of 192g of saturated fat, some 8 or 9 times more than the USDA recommend the average person eat in a day.

Just 13 days later, another blood draw returned an LDL-C of 180 mg/dl. In the intervening days, I consumed a maximum of 152g of saturated fat and averaged only 83g per day. Clearly, saturated fat consumption didn’t drive the extreme increase in LDL-C, as it is traditionally thought to do. So, what happened?

The important missing information is that the second blood draw came on day 3 of an extended fast, meaning I had literally consumed nothing – zero grams of fat – the two days prior. My LDL-C was elevated for the exact reasons that have been outlined at length in these writings – increasing LDL-C is an unavoidable consequence of utilizing fat for energy.

 

Low-Carb Trials and LDL-C

We don’t need to rely on my stories for evidence though – studies indeed demonstrate that healthy individuals will see a rise in LDL-C during extended fasting.^1,2 Healthy individuals moving to a very low-carbohydrate diet experience the same, just as we would expect.^3–7 Note the use of the word “healthy” here – these are individuals without significant metabolic dysfunction. They neatly fit the profile we’ve described of a metabolically healthy individual with excellent health markers that experience an increase in LDL-C as a consequence of trafficking triglycerides for energy.

But what if they weren’t healthy? Imagine instead a study that enrolled only those with metabolic dysfunction, obesity, and insulin resistance. These individuals might very well already have elevated LDL-C alongside poor markers of metabolic health, a consequence of poor triglyceride utilization, increased return of triglycerides to the liver, and compensatory VLDL production. The traditional cholesterol paradigm would likely be aghast at the suggestion that these individuals consume more fat, with their LDL-C already considered a risk to their health and the increased fat, surely, likely to elevate it even further.

But of course, this is not what happens. As many studies that demonstrated, the common finding in these individuals is indeed lower LDL-C following the transition to a low-carb, high-fat diet.^8–21 Of course, an energy delivery model of lipid metabolism explains clearly why this is the case – reduced blood sugar and insulin levels allow for improved fatty acid utilization, increased triglyceride clearance, reduced triglyceride return to the liver, and the gradual reduction of excess VLDL production. Much like my fasting example above, a traditional paradigm that suggests fat consumption as the prime driver of elevated LDL-C levels simply cannot explain these observations.

(You may notice here that these findings, taken together, suggest that over a long enough time frame an obese individual restricting carbohydrates would experience BOTH an initial decrease in LDL-C and then again increasing LDL-C levels following a return to normal weight and metabolic health. Of course, every other possible marker of health – HDL-C, triglycerides, blood sugar, body fat, blood pressure, etc. – would be much closer to optimal by the end of this journey)

 

Conclusion

If you’ve read the first eleven sections on this topic, nothing written above is surprising or even new. While the traditional paradigm continues to stress carbohydrate consumption in an effort to lower LDL-C, it is overwhelmingly clear that this approach may or may not have the desired effect but will certainly contribute to worsening metabolic health. I’ll end this series with the conclusion from my paper on cholesterol and lipid metabolism:

 

“This paper is absolutely not intended to make the argument that elevated LDL-C via an energy-driven increase in endogenous VLDL production is a metabolic state for which one need necessarily strive. Instead, this particular metabolic presentation is examined at length because it succinctly highlights the failure of the lipid-heart and diet-heart hypotheses that have undermined public health for decades. It is not a metabolic state towards which one needs to strive, but, far more importantly, it is also does not appear to be a metabolic state of which one needs to be afraid. The full body of scientific evidence, massive in both scope and depth, makes this incredibly clear.

What this paper is meant to argue is that the myopic focus on LDL-C and total cholesterol and the demonization of dietary fat must begin receding from medical, nutritional, and public consciousness if chronic health is to improve in western society. It is absolutely meant to highlight the indisputable evidence that every legitimate marker of chronic and cardiometabolic health – HDL-C, triglycerides, modified LDL particles, and others – has been repeatedly and overwhelmingly demonstrated to improve with a decrease in carbohydrate consumption. The understanding that poor triglyceride utilization, driven by insulin resistance and excess carbohydrate consumption, is the primary factor in metabolic dysfunction is crucial to recognizing the failure of conventional guidelines in addressing these risk factors. An energy deliver model of lipid metabolism best explains the available interventional evidence and wide range of lipid observations, existing in stark contrast to the abject catastrophe that is an entrenched paradigm of outdated and anti-scientific dogma pushing unsuspecting persons quickly and aggressively towards dyslipidemia, disease, and death.

The lipid-heart hypothesis has been allowed to survive for so long because the broad relationship between LCL-C and cardiovascular disease will always exist in an insulin resistant population that overconsumes carbohydrates. While the relationship is loosely valid in a diseased population, it should not be considered good enough for the purposes of preventing or especially treating cardiometabolic disease. Instead, the goal in both cases must be to prevent or reverse the underlying insulin resistance and the host of hyperglycemia-induced damages that occur alongside it. Only when this happens, when lipids are fairly viewed as an energy delivery system rather than as a disease state, can cardiovascular, metabolic, and chronic health truly be improved.”

 

 

Key takeaways

• LDL-C is increased when a metabolically healthy person significantly reduces carbohydrate consumption, either through fasting or a low-carb diet
• LDL-C is reduced when a person with poor metabolic health reduces carbohydrates, because previous elevations were driven by metabolic dysfunction rather than fat consumption
• Advocacy for an increase in carbohydrate consumption has variable effects on LDL-C, a marker with little to no independent relationship with cardiovascular disease, while clearly and consistently worsening every other marker of cardiometabolic health

 

1.               Browning JD, Baxter J, Satapati S, Burgess SC. The effect of short-term fasting on liver and skeletal muscle lipid, glucose, and energy metabolism in healthy women and men. Journal of Lipid Research. 2012;53(3):577-586. doi:10.1194/jlr.P020867

2.               Sävendahl L, Underwood LE. Fasting Increases Serum Total Cholesterol, LDL Cholesterol and Apolipoprotein B in Healthy, Nonobese Humans. The Journal of Nutrition. 1999;129(11):2005-2008. doi:10.1093/jn/129.11.2005

3.               Volek JS, Sharman MJ, Gómez AL, Scheett TP, Kraemer WJ. An Isoenergetic Very Low Carbohydrate Diet Improves Serum HDL Cholesterol and Triacylglycerol Concentrations, the Total Cholesterol to HDL Cholesterol Ratio and Postprandial Lipemic Responses Compared with a Low Fat Diet in Normal Weight, Normolipidemic Women. The Journal of Nutrition. 2003;133(9):2756-2761. doi:10.1093/jn/133.9.2756

4.               Huntriss R, Campbell M, Bedwell C. The interpretation and effect of a low-carbohydrate diet in the management of type 2 diabetes: a systematic review and meta-analysis of randomised controlled trials. Eur J Clin Nutr. 2018;72(3):311-325. doi:10.1038/s41430-017-0019-4

5.               Sharman MJ, Kraemer WJ, Love DM, et al. A Ketogenic Diet Favorably Affects Serum Biomarkers for Cardiovascular Disease in Normal-Weight Men. The Journal of Nutrition. 2002;132(7):1879-1885. doi:10.1093/jn/132.7.1879

6.               Lee HS, Lee J. Influences of Ketogenic Diet on Body Fat Percentage, Respiratory Exchange Rate, and Total Cholesterol in Athletes: A Systematic Review and Meta-Analysis. International Journal of Environmental Research and Public Health. 2021;18(6):2912. doi:10.3390/ijerph18062912

7.               Burén J, Ericsson M, Damasceno NRT, Sjödin A. A Ketogenic Low-Carbohydrate High-Fat Diet Increases LDL Cholesterol in Healthy, Young, Normal-Weight Women: A Randomized Controlled Feeding Trial. Nutrients. 2021;13(3):814. doi:10.3390/nu13030814

8.               Hussain TA, Mathew TC, Dashti AA, Asfar S, Al-Zaid N, Dashti HM. Effect of low-calorie versus low-carbohydrate ketogenic diet in type 2 diabetes. Nutrition. 2012;28(10):1016-1021. doi:10.1016/j.nut.2012.01.016

9.               Westman EC, Yancy WS, Edman JS, Tomlin KF, Perkins CE. Effect of 6-month adherence to a very low carbohydrate diet program. The American Journal of Medicine. 2002;113(1):30-36. doi:10.1016/S0002-9343(02)01129-4

10.             Foster GD, Wyatt HR, Hill JO, et al. Weight and Metabolic Outcomes After 2 Years on a Low-Carbohydrate Versus Low-Fat Diet. Ann Intern Med. 2010;153(3):147-157. doi:10.7326/0003-4819-153-3-201008030-00005

11.             Lim SS, Noakes M, Keogh JB, Clifton PM. Long-term effects of a low carbohydrate, low fat or high unsaturated fat diet compared to a no-intervention control. Nutrition, Metabolism and Cardiovascular Diseases. 2010;20(8):599-607. doi:10.1016/j.numecd.2009.05.003

12.             Iqbal N, Vetter ML, Moore RH, et al. Effects of a Low-intensity Intervention That Prescribed a Low-carbohydrate vs. a Low-fat Diet in Obese, Diabetic Participants. Obesity. 2010;18(9):1733-1738. doi:10.1038/oby.2009.460

13.             Dansinger ML, Gleason JA, Griffith JL, Selker HP, Schaefer EJ. Comparison of the Atkins, Ornish, Weight Watchers, and Zone Diets for Weight Loss and Heart Disease Risk ReductionA Randomized Trial. JAMA. 2005;293(1):43-53. doi:10.1001/jama.293.1.43

14.             Maki KC, Beiseigel JM, Jonnalagadda SS, et al. Whole-Grain Ready-to-Eat Oat Cereal, as Part of a Dietary Program for Weight Loss, Reduces Low-Density Lipoprotein Cholesterol in Adults with Overweight and Obesity More than a Dietary Program Including Low-Fiber Control Foods. Journal of the American Dietetic Association. 2010;110(2):205-214. doi:10.1016/j.jada.2009.10.037

15.             Harman NL, Leeds AR, Griffin BA. Increased dietary cholesterol does not increase plasma low density lipoprotein when accompanied by an energy-restricted diet and weight loss. Eur J Nutr. 2008;47(6):287. doi:10.1007/s00394-008-0730-y

16.             Lofgren I, Zern T, Herron K, et al. Weight loss associated with reduced intake of carbohydrate reduces the atherogenicity of LDL in premenopausal women. Metabolism. 2005;54(9):1133-1141. doi:10.1016/j.metabol.2005.03.019

17.             Klempel MC, Kroeger CM, Bhutani S, Trepanowski JF, Varady KA. Intermittent fasting combined with calorie restriction is effective for weight loss and cardio-protection in obese women. Nutr J. 2012;11(1):98. doi:10.1186/1475-2891-11-98

18.             Dashti H, Bo-Abbas Y, Asfar S, et al. Ketogenic diet modifies the risk factors of heart disease in obese patients. Nutrition (Burbank, Los Angeles County, Calif). 2003;19:901-902. doi:10.1016/S0899-9007(03)00161-8

19.             Dashti HM, Mathew TC, Khadada M, et al. Beneficial effects of ketogenic diet in obese diabetic subjects. Mol Cell Biochem. 2007;302(1):249-256. doi:10.1007/s11010-007-9448-z

20.             Dashti HM, Mathew TC, Hussein T, et al. Long-term effects of a ketogenic diet in obese patients. Exp Clin Cardiol. 2004;9(3):200-205.

21.             Dashti HM, Al-Zaid NS, Mathew TC, et al. Long Term Effects of Ketogenic Diet in Obese Subjects with High Cholesterol Level. Mol Cell Biochem. 2006;286(1):1. doi:10.1007/s11010-005-9001-x

The Problematic Paradigm of LDL-C, Part 11

Part 11 - The Effects of Diet on Markers of Cardiovascular and Metabolic Health

Previous - Part 10 - Other Factors in the Development of Atherosclerosis

Now that we’ve thoroughly examined the manner by which poor metabolic health can lead to small, damaged LDL particles and compromised blood vessels, lets finish our exploration of the LDL disease paradigm by examining common health markers and the effects of dietary choices on each.  

 

Impaired Metabolic Health

As has been made extremely clear by now, an individual with poor lipid metabolism will have several characteristic features. They will take up triglycerides slowly and inefficiently, which increases both the lifespan and the triglyceride count of the VLDL particles that transport them. This will lead to increased trading with HDL and LDL particles in order to share the excess triglyceride burden that must return to the liver. As a result, HDL-C will do down, while triglyceride-rich LDL particles will be acted on at the liver and reduced in size. This leads to a preponderance of small, dense LDL particles that are prime targets for modification, damage, and an immune response instrumental in atherosclerotic development.

Let’s walk through several of these and other markers one at a time, highlighting dozens of controlled trials that have sought to examine how dietary choices affect each of them.

 

Triglycerides

High triglycerides levels, as we have explored, are not primarily indicative of high triglyceride production but instead of poor triglyceride uptake by the cells of the body. This is effectively where metabolic dyslipidemia begins; Many other markers of poor metabolic health – low HDL-C, high VLDL-C, etc. – stem directly from the surplus of triglycerides in the blood of a person who cannot effectively utilize them.

Conventional advice on triglyceride lowering is mixed, but improving. Some authoritative sources, such as the Mayo Clinic, correctly blame high carbohydrate consumption above all else as a cause of elevated triglycerides (“If you regularly eat more calories than you burn, particularly from high-carbohydrate foods, you may have high triglycerides”).¹ However, this position is hardly unanimous. Recent guidelines on triglyceride management from the American College of Cardiology include the advice that “clinicians are advised to further reduce TGs with a very low-fat diet.”²

The scientific literature on this topic, however, is extremely clear. To my knowledge (and believe me, I’ve looked), there does not yet exist a controlled trial in which the replacement of fat with carbohydrates has demonstrated a reduction in triglycerides. On the contrary, it is a fairly trivial task to find dozens that demonstrate the opposite.^3–55 The reasons for this are multiple:

• Elevated blood sugar causes glucose to be preferentially burned in an effort to return blood sugar levels to normal, inhibiting fat-utilization and essentially leaving triglycerides to accumulate as they wait to be taken up.
• Long-term exposure to excess carbohydrates can lead to chronically elevated insulin and potential insulin resistance, making it more difficult for some cells to take in triglycerides.  
• Some carbohydrates (fructose, most specifically) are directly converted to triglycerides in the liver. Thus it is common to heavily utilize carbs for energy while also creating new triglycerides that can’t presently be taken up.

In short – in order to lower triglycerides, one must eat fewer carbohydrates and “teach” the body to begin utilizing fat at a more efficient rate.

 

HDL-C

The largest factor in HDL-C levels is of course the degree to which HDL particles must trade away cholesterol in order to take on triglycerides from heavily-burdened VLDL particles. It should be no surprise whatsoever, then, that the science on HDL-C is just as consistently clear and overwhelming as is the science of triglycerides. When one eats too many carbohydrates, HDL-C goes down.^{6,15,21,23,27,30–34,41–43,47,48,54,56–71}

This is not the only way diet can affect HDL however. A high HDL particle count is also associated with decreased risk for cardiovascular disease, and tends to increase alongside HDL-C. High fat consumption drives further production of apoA1, the main structural component of HDL particles.^71–75 Unsurprisingly, then, greater fat consumption is associated with increased HDL particle count.^66,76–79

Again we see that in order to improve HDL-C levels, one absolutely must replace some dietary carbohydrates with fat. 

 

VLDL-C

This one should be fairly clear as well. Because poor triglyceride utilization both increases the risk for cardiovascular disease and increases the lifespan of a triglyceride-rich VLDL particle, it meets all expectations that studies show a strong connection between elevated VLDL-C and cardiovascular disease.^80–84

Equally as expected, trials routinely indicate that reducing carbohydrate intake improves VLDL-C levels.^8,37,85–88

 

LDL particle size and sdLDL  

The reasons for the strong association between decreased LDL particle size and increased cardiovascular risk have been detailed at length – poor triglyceride utilization and increased return of triglycerides to the liver drives these changes. Again, as was the case with the previous markers, numerous trials have demonstrated that increased carbohydrate consumption at the expense of fat drives an increase in sdLDL and a decrease in average LDL particle size.^{4,36,37,76,77,89–94}

 

Other factors

The markers outlined above are common health markers and major players in lipid metabolism that have been extensively demonstrated to improve with reduced carbohydrate consumption. Many other factors are affected by carbohydrate consumption as well, including:

• Oxidized LDL – Decreasing the glycemic load, decreasing fructose consumption, and increasing fat consumption have all been demonstrated to reduce levels of oxidized LDL particles.^95–101
• lipoprotein(a) – lp(a), an LDL-like particle considered to be particularly atherogenic, serves as a primary carrier of oxidized lipoproteins. While many incorrectly assume lp(a) levels to be genetically fixed, they can in fact be lowered through increased saturated fat consumption.^101–104
• The primary reason the above points are true is because highly unsaturated fatty acids (such as those found in seed oils like corn, soybean, canola, etc.) are more reactive than saturated fatty acids and those more susceptible to modification. This may be exacerbated by the inflammatory conditions consistent with long-term elevated blood sugar.
• Hyperglycemia decreases the availability of nitric oxide, contributing to increases in oxidized LDL and impairing vascular integrity.^105–109
• Hyperglycemia increases the expression of the free radical-generating NADPH oxidase and the immune-modulating protein NF-kB, instrumental in the inflammatory immune response that binds LDL particles at the walls of the blood vessel.^110–117
• Hyperglycemia both damages and impairs rebuilding of the protective glycocalyx that lines the walls of the blood vessels. ^118–122

 

Hundreds of studies demonstrate that these and other risk factors for cardiovascular disease are made worse by increasing adherence to a carbohydrate-heavy diet. The reasons for this are readily apparent with an understanding of lipid mechanics, and the ways in which poor triglyceride utilization and excess blood sugar lead to a variety of atherogenic conditions. There is one metric left to examine though – LDL-C – which we’ll cover in the next, and final, section.

 

**Key Takeaways

• Every common cardiometabolic marker (leaving aside LDL-C) reliably and consistently improves with a decrease in carbohydrate consumption and an increase in fat
• Modification and damage to both LDL particles and the overall vascular environment is increased by the presence of excess carbohydrate in the bloodstream

 

Part 12 - The Effects of Diet of LDL-C, As Told By Energy Delivery

1.               Triglycerides: Why do they matter? - Mayo Clinic. Accessed April 22, 2023. https://www.mayoclinic.org/diseases-conditions/high-blood-cholesterol/in-depth/triglycerides/art-20048186

2.               Hypertriglyceridemia Management According to the 2018 AHA/ACC Guideline. American College of Cardiology. Accessed August 12, 2022. https://www.acc.org/latest-in-cardiology/articles/2019/01/11/07/39/http%3a%2f%2fwww.acc.org%2flatest-in-cardiology%2farticles%2f2019%2f01%2f11%2f07%2f39%2fhypertriglyceridemia-management-according-to-the-2018-aha-acc-guideline

3.               Volek JS, Sharman MJ, Gómez AL, Scheett TP, Kraemer WJ. An Isoenergetic Very Low Carbohydrate Diet Improves Serum HDL Cholesterol and Triacylglycerol Concentrations, the Total Cholesterol to HDL Cholesterol Ratio and Postprandial Lipemic Responses Compared with a Low Fat Diet in Normal Weight, Normolipidemic Women. The Journal of Nutrition. 2003;133(9):2756-2761. doi:10.1093/jn/133.9.2756

4.               Forsythe CE, Phinney SD, Feinman RD, et al. Limited Effect of Dietary Saturated Fat on Plasma Saturated Fat in the Context of a Low Carbohydrate Diet. Lipids. 2010;45(10):947-962. doi:10.1007/s11745-010-3467-3

5.               Mousavi SM, Ejtahed HS, Marvasti FE, et al. The Effect of a Moderately Restricted Carbohydrate Diet on Cardiometabolic Risk Factors in Overweight and Obese Women With Metabolic Syndrome: A Randomized Controlled Trial. Clinical Therapeutics. Published online March 4, 2023. doi:10.1016/j.clinthera.2023.02.002

6.               Foster GD, Wyatt HR, Hill JO, et al. A Randomized Trial of a Low-Carbohydrate Diet for Obesity. New England Journal of Medicine. 2003;348(21):2082-2090. doi:10.1056/NEJMoa022207

7.               Yamada Y, Uchida J, Izumi H, et al. A Non-calorie-restricted Low-carbohydrate Diet is Effective as an Alternative Therapy for Patients with Type 2 Diabetes. Internal Medicine. 2014;53(1):13-19. doi:10.2169/internalmedicine.53.0861

8.               Parks EJ, Krauss RM, Christiansen MP, Neese RA, Hellerstein MK. Effects of a low-fat, high-carbohydrate diet on VLDL-triglyceride assembly, production, and clearance. J Clin Invest. 1999;104(8):1087-1096. doi:10.1172/JCI6572

9.               Chiu S, Bergeron N, Williams PT, Bray GA, Sutherland B, Krauss RM. Comparison of the DASH (Dietary Approaches to Stop Hypertension) diet and a higher-fat DASH diet on blood pressure and lipids and lipoproteins: a randomized controlled trial1–3. The American Journal of Clinical Nutrition. 2016;103(2):341-347. doi:10.3945/ajcn.115.123281

10.             Properzi C, O’Sullivan TA, Sherriff JL, et al. Ad Libitum Mediterranean and Low-Fat Diets Both Significantly Reduce Hepatic Steatosis: A Randomized Controlled Trial. Hepatology. 2018;68(5):1741-1754. doi:10.1002/hep.30076

11.             Bradley U, Spence M, Courtney CH, et al. Low-Fat Versus Low-Carbohydrate Weight Reduction Diets: Effects on Weight Loss, Insulin Resistance, and Cardiovascular Risk: A Randomized Control Trial. Diabetes. 2009;58(12):2741-2748. doi:10.2337/db09-0098

12.             Marckmann P, Sandström B, Jespersen J. Low-fat, high-fiber diet favorably affects several independent risk markers of ischemic heart disease: observations on blood lipids, coagulation, and fibrinolysis from a trial of middle-aged Danes. The American Journal of Clinical Nutrition. 1994;59(4):935-939. doi:10.1093/ajcn/59.4.935

13.             Bazzano LA, Hu T, Reynolds K, et al. Effects of Low-Carbohydrate and Low-Fat Diets. Ann Intern Med. 2014;161(5):309-318. doi:10.7326/M14-0180

14.             Ebbeling CB, Leidig MM, Feldman HA, Lovesky MM, Ludwig DS. Effects of a Low–Glycemic Load vs Low-Fat Diet in Obese Young AdultsA Randomized Trial. JAMA. 2007;297(19):2092-2102. doi:10.1001/jama.297.19.2092

15.             Dashti HM, Mathew TC, Hussein T, et al. Long-term effects of a ketogenic diet in obese patients. Exp Clin Cardiol. 2004;9(3):200-205.

16.             Abbasi F, McLaughlin T, Lamendola C, et al. High carbohydrate diets, triglyceride-rich lipoproteins, and coronary heart disease risk. The American Journal of Cardiology. 2000;85(1):45-48. doi:10.1016/S0002-9149(99)00604-9

17.             Shai I, Schwarzfuchs D, Henkin Y, et al. Weight Loss with a Low-Carbohydrate, Mediterranean, or Low-Fat Diet. New England Journal of Medicine. 2008;359(3):229-241. doi:10.1056/NEJMoa0708681

18.             Brinkworth GD, Noakes M, Buckley JD, Keogh JB, Clifton PM. Long-term effects of a very-low-carbohydrate weight loss diet compared with an isocaloric low-fat diet after 12 mo. The American Journal of Clinical Nutrition. 2009;90(1):23-32. doi:10.3945/ajcn.2008.27326

19.             Hudgins LC, Hellerstein M, Seidman C, Neese R, Diakun J, Hirsch J. Human fatty acid synthesis is stimulated by a eucaloric low fat, high carbohydrate diet. J Clin Invest. 1996;97(9):2081-2091. doi:10.1172/JCI118645

20.             Nordmann AJ, Nordmann A, Briel M, et al. Effects of Low-Carbohydrate vs Low-Fat Diets on Weight Loss and Cardiovascular Risk Factors: A Meta-analysis of Randomized Controlled Trials. Archives of Internal Medicine. 2006;166(3):285-293. doi:10.1001/archinte.166.3.285

21.             Ruth MR, Port AM, Shah M, et al. Consuming a hypocaloric high fat low carbohydrate diet for 12weeks lowers C-reactive protein, and raises serum adiponectin and high density lipoprotein-cholesterol in obese subjects. Metabolism. 2013;62(12):1779-1787. doi:10.1016/j.metabol.2013.07.006

22.             Parillo M, Rivellese AA, Ciardullo AV, et al. A high-monounsaturated-fat/low-carbohydrate diet improves peripheral insulin sensitivity in non-insulin-dependent diabetic patients. Metabolism. 1992;41(12):1373-1378. doi:10.1016/0026-0495(92)90111-M

23.             Huntriss R, Campbell M, Bedwell C. The interpretation and effect of a low-carbohydrate diet in the management of type 2 diabetes: a systematic review and meta-analysis of randomised controlled trials. Eur J Clin Nutr. 2018;72(3):311-325. doi:10.1038/s41430-017-0019-4

24.             Martens EA, Gatta-Cherifi B, Gonnissen HK, Westerterp-Plantenga MS. The Potential of a High Protein-Low Carbohydrate Diet to Preserve Intrahepatic Triglyceride Content in Healthy Humans. PLOS ONE. 2014;9(10):e109617. doi:10.1371/journal.pone.0109617

25.             Sanfelippo ML, Swenson RS, Reaven GM. Reduction of plasma triglycerides by diet in subjects with chronic renal failure. Kidney International. 1977;11(1):54-61. doi:10.1038/ki.1977.7

26.             Stern L, Iqbal N, Seshadri P, et al. The Effects of Low-Carbohydrate versus Conventional Weight Loss Diets in Severely Obese Adults: One-Year Follow-up of a Randomized Trial. Ann Intern Med. 2004;140(10):778-785. doi:10.7326/0003-4819-140-10-200405180-00007

27.             Volek JS, Sharman MJ. Cardiovascular and Hormonal Aspects of Very-Low-Carbohydrate Ketogenic Diets. Obesity Research. 2004;12(S11):115S-123S. doi:10.1038/oby.2004.276

28.             Hays JH, DiSabatino A, Gorman RT, Vincent S, Stillabower ME. Effect of a high saturated fat and no-starch diet on serum lipid subfractions in patients with documented atherosclerotic cardiovascular disease. Mayo Clin Proc. 2003;78(11):1331-1336. doi:10.4065/78.11.1331

29.             Kirkpatrick CF, Bolick JP, Kris-Etherton PM, et al. Review of current evidence and clinical recommendations on the effects of low-carbohydrate and very-low-carbohydrate (including ketogenic) diets for the management of body weight and other cardiometabolic risk factors: A scientific statement from the National Lipid Association Nutrition and Lifestyle Task Force. Journal of Clinical Lipidology. 2019;13(5):689-711.e1. doi:10.1016/j.jacl.2019.08.003

30.             Schwingshackl L, Hoffmann G. Comparison of Effects of Long-Term Low-Fat vs High-Fat Diets on Blood Lipid Levels in Overweight or Obese Patients: A Systematic Review and Meta-Analysis. Journal of the Academy of Nutrition and Dietetics. 2013;113(12):1640-1661. doi:10.1016/j.jand.2013.07.010

31.             Chawla S, Tessarolo Silva F, Amaral Medeiros S, Mekary RA, Radenkovic D. The Effect of Low-Fat and Low-Carbohydrate Diets on Weight Loss and Lipid Levels: A Systematic Review and Meta-Analysis. Nutrients. 2020;12(12):3774. doi:10.3390/nu12123774

32.             Dashti H, Bo-Abbas Y, Asfar S, et al. Ketogenic diet modifies the risk factors of heart disease in obese patients. Nutrition (Burbank, Los Angeles County, Calif). 2003;19:901-902. doi:10.1016/S0899-9007(03)00161-8

33.             Dashti HM, Mathew TC, Khadada M, et al. Beneficial effects of ketogenic diet in obese diabetic subjects. Mol Cell Biochem. 2007;302(1):249-256. doi:10.1007/s11010-007-9448-z

34.             Yancy WS, Olsen MK, Guyton JR, Bakst RP, Westman EC. A Low-Carbohydrate, Ketogenic Diet versus a Low-Fat Diet To Treat Obesity and Hyperlipidemia. Ann Intern Med. 2004;140(10):769-777. doi:10.7326/0003-4819-140-10-200405180-00006

35.             Dashti HM, Al-Zaid NS, Mathew TC, et al. Long Term Effects of Ketogenic Diet in Obese Subjects with High Cholesterol Level. Mol Cell Biochem. 2006;286(1):1. doi:10.1007/s11010-005-9001-x

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