De Novo Lipo-what?

Humans have limited capacity to store carbohydrates. Beyond the glucose and glycogen in our blood and tissues, we have relatively little carbohydrate to draw from in time of energy need. That's why long-distance runners and triathletes have to carry sugar sources to keep blood sugar from plummeting.

Fat, of course, is different. We have virtually unlimited capacity to store energy as fat.

Because we have limited carbohydrate storage capacity, what can the body do with the excessive quantities of carbohydrates that Americans ingest? What becomes of a bagel for breakfast, wheat crackers for snacks, a whole wheat sandwich for lunch, pretzels, and whole wheat pasta that many people eat every day, not to mention the chips, soft drinks, and juices?

Excess carbohydrates are diverted to an interesting metabolic pathway called de novo lipogenesis (DNL). This refers to the liver's ability to make triglycerides from excessive carbohydrates in the diet. Triglycerides are packaged for release into the blood as VLDL. VLDL, in turn, interacts with other lipoproteins, creating small LDL particles, reduced HDL and smaller, less protective HDL. High VLDL will be measured on a standard cholesterol panel as higher triglycerides.

A University of California (Berkeley, San Francisco) group has done much of the work describing DNL.

A diet weighed towards carbohydrates, especially if 50% or greater calories are carbohydrate, is sufficient to provoke plenty of DNL, even in slender people. DNL is a big part of the reason why low-fat (and, thereby, high-carbohydrate) diets result in higher triglycerides. DNL really gets turned on many-fold if the carbohydrates are "simple," rather than "complex."

Overweight people, however, can demonstrate five-fold greater DNL even with lesser quantities of carbohydrate intake (e.g., 40% fat, 46% carbohydrate, 14% protein):

From Schwarz et al 2003. Mean (± SEM) fractional de novo lipogenesis in lean normoinsulinemic (NI), obese NI, and obese hyperinsulinemic (HI) subjects after 5 d of consuming a high-fat, low-carbohydrate diet and in different lean NI and obese HI subjects after 5 d of consuming a low-fat, high-carbohydrate diet. Values with different superscript letters are significantly different.

Excessive carbohydrates, a la standard low-fat diets, are good for nobody. The concept of de novo lipogenesis fills in a theoretical hole that now explains why people who eat carbohydrates have higher triglycerides, VLDL, and, eventually, insulin resistance and diabetes.

Comments (16) -

  • Dave

    1/5/2010 5:11:24 PM |

    Just how do higher VLDL and higher triglycerides promote insulin resistance?

  • Anonymous

    1/5/2010 6:03:32 PM |

    Dr. Davis, I've just recently stumbled upon this blog and I love it.  Thank you for so generously sharing your insights.

    I was wondering if would suggest any different dietary guidelines for people with familial hypercholesterolemia.  In particular, I have heterozygous FH for which I am taking 40mg Crestor, but I am an otherwise healthy, lean 25 year old male with lipid numbers of 47 Trig / 169 LDL (calculated)/ 73 HDL.  I closely follow a paleo/primal diet and fitness routine so I am hoping the LDL is the large and in little danger of oxidation.

    To any other FHers out there, I would be happy to hear about your experiences.


  • Anonymous

    1/5/2010 9:54:50 PM |

    46% carbs is still high in my opinion. I tend to agree with Dr. Eades in the book Protein Power where your carb requirements should not exceed 1.3 times your protein requirements and that should be based on lean body mass and activity level. The rest fat, mostly saturated animal fat. Tropical oils are great too.

  • Anonymous

    1/5/2010 10:45:04 PM |

    Does this chart, which shows that HI people have much higher DNL on a low-carb diet, explain Gretchen's result in your previous article?  She is HI (hyperinsulinemic), right?

    So people on a low-carb/high-fat diet who have normal levels of insulin will not experience the post-prandial spike in triglycerides that Gretchen did.

  • Anonymous

    1/6/2010 1:56:22 PM |

    DNL really gets turned on many-fold if the triglycerides are "simple," rather than "complex."

    Could you please explain the difference between 'simple' and 'complex' triglycerides.


  • LynneC

    1/6/2010 7:27:38 PM |

    Anonymous re familial Hz hypercholesterolemia.  I, too, am Hz and started with the Track your Plaque (Dr Davis') program about 4 months ago. I think that you have stumbled upon the best diet for this condition. (paleo/ low-carb) I am trying to find that balance of the least amount of Crestor that I can take vs how much sat fat I can add to my diet while keeping my LDL in line.
    I was on a weekly total of 80 mg Crestor, and my LDL-c was 170 as of 2 weeks ago. My LDL particle count is still too high, so I have just started to add another 20mg dose per week.  I take it every other day, so my new weekly total of Crestor will be 100mg.

    You should consider joing the Track your Plaque program that is run by Dr Davis.  There many great discussions there and some very sharp minds that contribute to the discussion forum.

    At the very least, get an NMR lipid profile done; this will let you know the most important aspect of your LDL, which is the number of particles that comprise it.

  • Dr. William Davis

    1/7/2010 3:27:39 AM |

    A point of clarification: Fat intake leads to high postprandial triglycerides--there is absolutely no doubt about this. This occurs regardless of insulin sensitivity, body weight, carbohydrate content of the meal, etc.

    Fat = triglycerides. When you eat fat, triglycerides go up postprandially.

  • Dr. William Davis

    1/7/2010 3:29:18 AM |


    Simple carbohydrates = simple sugars like candy, soft drinks, juices: immediately absorbed, no fiber

    Complex carbohydrates = carbohydrates that occur in polymers or bound up in fibers, less rapidly absorbed.

    In my mind, both are undesirable, though complex are less undesirable.

  • Dave

    1/7/2010 5:43:55 AM |

    Dr. Davis, surely you don't mean *all* complex carbohydrates are undesirable, do you?  Carbohydrates from, say, sweet potatoes and oat bran must be (more than) just fine, on balance.  And as to fat, might the solution be to increase good fat (mono and omega-3) but avoid saturated and trans fat?

  • Dr.A

    1/7/2010 12:14:22 PM |

    Great post! I have just completed a university nutrition course... knowing that carbs turn to fat easily I was stunned to find the following in my course text:
    The amount of glycogen that can be stored is quite limited(no more than a few hundred grams in total), so the stores are filled quite quickly and if more glucose is available, then the excess could be converted into fat for storage. Fat stores in the body are effectively unlimited. However, it appears that excess carbohydrate is normally used for energy rather than being converted to fat.

  • Ryan Koch @ Health Matters to Me

    1/9/2010 6:42:36 PM |

    Dr. Davis,

    Aren't the results of the study questionable due to the fact that the participants' diet was prepared in a laboratory and may have consisted of health-altering foods (i.e. gluten, artificial fructose, trans fats, veggie oils)?  Do they list the diet composition in the study?  I may have missed it.

    Also, regarding runners and their fuel sources: I've read that Ethiopian runners don't hit "the wall" like runners in more modern cultures do.  This means they have an efficient fat-burning metabolism, correct?  Their diet composition is mostly starchy non-gluten carbs:

    "Diet was high in carbohydrate (76.5%, 0.4 g/kg BM per day) and low in fat (13.4 %)."
    Food and macronutrient intake of elite kenyan distance runners


  • Anonymous

    3/29/2010 9:49:16 AM |

    "However, it appears that excess carbohydrate is normally used for energy rather than being converted to fat."

    That's true. The biggest impact of carbs is that they are used for energy first, which means more of the fat consumed can be stored. This has been proven with radioactive studies that show that most of the fat in your body comes from fat in food, not from carbs. Of course, if you consume enough carbs, then those too will be converted to fat. Also, whether carbs directly become fat or not, the outcome is the same: more fat is stored in presence of more carbs.

  • MachineGhost

    5/25/2010 5:44:55 AM |

    Much of the confusion here seems to be the unawareness that different saturated fat subtypes have different post-prandial effects.  This was demonstrated by Hegsted eons ago and formulated into an equation.  Google it.

    Clearly, the predominant subtype of saturated fat in fatty meats is HARMFUL.  A HEALTHY high fat, low carbohydrate diet is EQUALLY BALANCED among the three fat macrotypes, not EXTREME to saturated fat.  Typically, studies just use the Atkins version of extreme high satirated fat, low carb.  A recent study showed that eating 1-2 slices of processed lunchmeat or 1 hot dog a day increases heart disease risk by 40% and diabetes by 20%, and that's on top of the increased risk of cancer from the nitrates.

    As far the high carb, low fat diet (S.A.D.), the culprit is the lack of soluble fiber which slows down post-prandial absorption.  The best at ameliorating this role is glucomannan.

    But people, don't kid yourself.  There are SEVENTEEN independent risk factors for heart disease.  You have to circumvent ALL of them to completely eliminate the risk.  A low, unrefined carb diet (<25% calories) with the remaining calories from balanced, unrefined fats and lean protein is a big part, but the rest involves influencing biochemistry and genetic expression via supplementation.

  • buy jeans

    11/3/2010 2:31:42 PM |

    A diet weighed towards carbohydrates, especially if 50% or greater calories are carbohydrate, is sufficient to provoke plenty of DNL, even in slender people. DNL is a big part of the reason why low-fat (and, thereby, high-carbohydrate) diets result in higher triglycerides. DNL really gets turned on many-fold if the triglycerides are "simple," rather than "complex.

  • ron

    1/1/2012 9:02:20 PM |

    Eat your complex carbs, and take a vegan algae-derived DHA/EPA supplement. Your triglycerides, if they're high, will drop like a stone. The healthiest, longest-lived, large populations on the planet eat starch-based diets.

  • Kirk

    1/4/2012 10:40:50 PM |

    If the problem with carbs is DNL, this implies that an amount up to where DNL is triggered is safe.  So I see why you recommend no more than 15 net carbs per meal.  Would this amount change for a (natural) body builder?  For example, i do 30 min strength training with weights at double my body weight.  I would like to replenish my muscles to prevent glycogen depletion.  Do you think it would be safe to increase the amount of carbs consumed in the post work out meal to 30 or 50g of complex carbs?