A Biochem Snapshot: 5 Facts That Keep Me Paleo

Diane Sanfilippo Biochemistry, Featured 19 Comments

Quick reminder for those of you reading this post on or before January 14, 2013 – The Toadally Primal Wellness Bundles of 33 eBooks for just $39 (a $479 value) ends at 11:59pm on 1/14/13 – don’t miss out! Get the details here.

Hey folks! Remember Courtney who you met not long ago? Well, here’s a great post from her – enjoy! – Diane


Being in grad school sometimes has its perks.

Beyond the chronically stressed, sleep-deprived state we regularly experience, there are moments of fulfillment and satisfaction. This past semester I participated in an advanced biochemistry class, which focused on macronutrient metabolism. Although at times it felt like this class could be the end of my sanity, the science I learned has really solidified my belief in ‘eating like our ancestors’. I’ve included the corresponding slides to show that I didn’t pull this stuff out of thin air (and maybe improve my street cred!).

Here are the Top 5 pearls of wisdom I learned about metabolism.

Hold on tight, it’s a little nerdy.

1. Consuming carbohydrate, especially in excess, can potentially increase the production of fat.

Enzymes related to Carb intake

When we consume carbohydrate, whether they are simple or complex, our insulin levels increase significantly. When insulin rises, enzymes are activated that help build fat molecules for storage in our adipose (fat) tissue. From an evolutionary perspective, it’s a protective mechanism to help us store energy after a “feast” which was often followed be “famine”. After a prolonged diet high in carbohydrate, these enzymes that help synthesize fat (in the form of triglycerides) will actually increase in quantity and therefore function. Without insulin, fat cannot be as easily produced in our fat cells for storage. This contradicts the idea of low-fat diets for fat loss.

Conclusion: Even if you don’t feed your body dietary fat, it will still make body fat it on its own.

Take home message: Be wary of refined/added sugars in food. Maintain a quality, optimal carbohydrate range depending on your activity level to keep your metabolism functioning efficiently, prevent unwanted weight gain, and enhance efforts to actually lose weight (if that’s your goal). The ideal range for grams of carbohydrate per day is generally less than 150 grams/day (See Mark Sisson’s work for more details. Note also that the USDA recommends approximately 300g/carbohydrates per day.), but certainly a lot more or a lot fewer would be required based on your metabolic state and activity levels. Consume whole food sources of carbohydrate such as potatoes and yuca, and refrain from excess or refined sugars to reach optimal health.

Still skeptical? Check out Mark Sisson’s post on the primal carbohydrate continuum. This idea is supported by several studies, including one from the Journal of Clinical Medicine and a more recent one published in Obesity: A Research Journal. 


2. Consuming fat increases the use of fat for energy.

This sounds like a broad statement, but stick with me here. If you adopt a higher fat diet over an extended period of time (i.e., days/weeks) your body will appropriately respond by increasing the utilization of fat for energy production. Scientifically speaking, the number of enzymes that are involved in the process of fat oxidation (energy production) will be increased over time. Pretty sweet, right? This opposes the widespread misconception that eating fat will cause you to gain bodily fat. This idea supports the paleo/primal recommendation to get adequate quality fat sources in our diet, including (but not limited to) those from well-raised animal products, egg yolks, coconut oil, extra virgin olive oil, avocado, and some raw nuts and seeds. Doing so will benefit our overall metabolism, ensure intake of fat-soluble vitamins, as well as aid in satiety.

Fat oxidation regulation

Conclusion: Our bodies are able to use fat for energy more efficiently when we eat more of it.

Take home message: Consume quality sources of fats on a daily basis. A significant amount of various fats in your diet, in combination with lower carbohydrate intake, can improve body composition by promoting the use of fat as an energy source. This will lessen reliance on sugar for energy, making your body more efficient at burning fat.

Still skeptical? Check out Mark Sisson’s Definitive Guide to the Primal Eating Plan. Here’s a study from the Journal of Applied Physiology addressing this topic.


3. Saturated fats have not been “solidly” linked to an increase risk for heart disease.

It appears that stearate (stearic acid), found in nice juicy steaks, has not been definitively shown to increase cardiovascular disease, as previously thought. Now we can all rest a little easier and enjoy those grass-fed steak dinners even more. (Did I mention chocolate and butter also contain stearic acid? Twist my arm.) There are some promising studies that discuss this exact topic; if you want to read more for yourself, references are provided at the end for your personal enjoyment.

The evidence says?

Conclusion: You can have your steak and eat it too.

Take home message: Enjoy some (grass-fed) red meat on a consistent basis; a steak, burger, meatballs, or something more creative – whatever floats your boat. Avoiding these quality meats for fear of ultimately giving yourself a heart attack is unnecessary, not to mention it will deprive you of amazing benefits and… deliciousness. Consume quality saturated fats found in nourishing animal products.

Still skeptical? Check out this study entitled, Saturated Fats and the Risk of Heart Disease. Here’s a review from the Lipids Journal, looking at evidence from similar studies focusing on saturated fat intake.


4. Plant sterols probably do more harm than good.

This point deals with mechanisms of cholesterol absorption. You may be familiar with the notion of replacing animal products with plant products in an effort to lower one’s cholesterol – the following illustrates just that.

Illustration of Cholesterol Transportation.

When we consume cholesterol and/or plant sterols in our food, they “compete” with each for absorption into our bodies. Specifically, when these compounds reach the cells in the lining of our gut, the cholesterol and plant sterols use the same cholesterol transporter, thus less cholesterol gets “in”. The plant sterols are (more or less) pumped back out by these transporters, and therefore cannot be substituted for cholesterol.

Therefore, consuming plant sterols does in fact play a role in lowering your serum cholesterol.

However, cholesterol is an extremely important component in our bodies. It is essential for the structure of membranes, production of steroid hormones, as well as bile/bile acids for digestion. The idea that cholesterol is directly responsible for elevated serum levels (and consequently heart disease) is becoming more and more debated. Don’t believe me? Here’s a thorough dissertation of this exact topic.

If you’re itching for more information, check out Chris Masterjohn’s material at .

Conclusion: Eating higher amounts of plant sterols will impair proper cholesterol absorption.

Take home message: Embrace cholesterol! Ideal sources include (pastured/grass-fed/local) eggs, butter, and organ meats. Cholesterol is a crucial molecule we need for normal function in our bodies. As shown above, elevated blood lipids are more associated with excess carbohydrate intake. And as far as plant sterols go, they’re basically unnecessary, and are typically sources such as highly processed vegetable oils including soybean, canola, etc. Chuck ’em out.

Still skeptical? Check out  Chris Masterjohn’s  work on why we need cholesterol so dearly. Cardiovascular Research from the European Society of Cardiology has published this recent study, questioning the use of plant sterols/stanols in the diet. Dr. Peter Attia also gives us a fantastic review of the complexities of cholesterol metabolism in his multi-part series The Straight Dope on Cholesterol


5. Omega-6/Omega-3 Polyunsaturated fats really matter in terms of inflammation.

Inflammation was only briefly discussed in this course, but I felt it was worth noting due to increased public interest. Similar to sterols and cholesterol, omega-6s and omega-3s compete with each other in the body, but the mechanism this time is different. Omega-6s are incorporated into the structure of other fats, such as phospholipids. When we experience inflammation, those omega-6 fatty acids are broken (cleaved) off, and are used in producing pro-inflammatory compounds. These compounds contribute to things like clotting, redness, and swelling, and are thought to play a role in many chronic diseases.

Where fatty acids are cleaved

The opposing role of omega-3’s here is crucial. Omega-3 fatty acids can replace the omega-6 at the same position of the phospholipid. When this fatty acid is cleaved off in response to inflammation, its effects are weaker, and shift more to an anti-clotting state.

Obviously, this is not implying that omega-6s should be avoided at all costs. To an extent, we need inflammation for immune responses as well as healing. However, the problem, especially in today’s society, is in the ratio  of omega-6 to omega-3 that most people are consuming.

Conclusion: Omega-6 and Omega-3 PUFAs should be in a balanced ratio to prevent negative effects of excess inflammation in the body and overall intake of PUFAs should be low relative to overall dietary fatty acid intake.

Take home message: Focus on eating omega-3 rich foods such as wild salmon, sardines, and mackerel to balance your overall ratio. This will markedly improve your body’s response to inflammation and prevent a chronically inflamed or overreactive state. Keep in mind that omega-3 sources from animal products are far more bioavailable (usable by the body) than plant sources.

Still skeptical? Check out this article  from the Center for Genetics, Nutrition and Health which addresses the importance of the ratio. Also, The Arizona Center for Advanced Medicine  has great information regarding the relationship nutrition and inflammation.


To quickly sum it all up:

  • Avoid refined foods, added sugars, and excess carbohydrate beyond what your body needs.
  • Consume adequate amounts of  high quality fats.
  • Select well-raised meats that aren’t devoid of their natural fats.
  • Choose foods with naturally occurring cholesterol via quality animal products.
  • Avoid excessive intake of inflammatory foods such as omega-6 polyunsaturated fats.

With nutrition recommendations coming from every direction these days, it is critical for us to understand the why and the how of what we eat. Scientific knowledge should be the foundation for nutrition recommendations, but sadly that is often not the case.

Thankfully, there is valid, clear-cut science behind the Paleo philosophy. This lifestyle has only been further reinforced by the unbiased information provided to me in an academic environment. The more I learn, the more I am convinced that Paleo is right for me.


Human fatty acid synthesis is stimulated by a eucaloric low fat, high carbohydrate diet.

Effect of Carbohydrate Overfeeding on Whole Body and Adipose Tissue Metabolism in Humans

Chronic AMP-activated protein kinase activation and a high-fat diet have an additive effect on mitochondria in rat skeletal muscle

Saturated Fat and Cardiometabolic Risk Factors, Coronary Heart Disease, Stroke, and Diabetes: a Fresh Look at the Evidence

Phytosterols and phytostanols: is it time to rethink that supplemented margarine?

The importance of the ratio of omega-6/omega-3 essential fatty acids.


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