Nutrition holding pen

ATP and acetyl-CoA

You cannot understand nutrition without understanding ATP. ATP is the end goal of digestion; it is the energy that allows us to stay alive. It is present in every living tissue. Without ATP you’re dead, like, right now. It’s that important.

ATP stands for adenosine triphosphate. (Don’t worry; we’ll stick to the acronym from here on out.) This compound contains one adenosine molecule attached to three phosphate groups. Hence the “tri- in triphosphate.” When you break a chemical bond—in this case, when you snap off a phosphate group—energy is released.

Think of ATP as the “energy currency” of the body. Though it may sound strange, your body can’t actually use the energy found in food; it has to convert that energy into ATP first. Only then we can use the energy from ATP.

Why?

Because food’s energy is stored in chemical bonds—namely, carbon and hydrogen bonds. But the energy released from these bonds are like a foreign currency to our bodies; sure, it has value, but you can’t use it here. Our bodies need to convert it into the local currency—which in our case, is ATP.

There is a shockingly small amount of ATP in your body at any given moment. It has to be recycled between 1,000 to 1,500 times per day. Put another way, you recycle your entire body weight in ATP every day. That’s a lot of energy!

Key point: Nutrition is basically the process of breaking hydrogen-carbon bonds in food, then using that energy to break apart the ATP bonds to create energy our bodies can actually use.

Metabolic pathways

Your metabolism refers to all the biochemical processes in your body. Although there are many different metabolic processes, they can be classified as either:

anabolic; which means “building up.” Examples include building muscle, new proteins, or storing fuel for later use.
catabolic; which means “breaking down.” Examples in include digestion, where food is broken down into smaller nutrients and absorbed by the body.

For our purposes, we can think of nutrition as breaking down food (via catabolic processes) and using the nutrients to keep our bodies functioning properly (via anabolic processes). If there is an absence of food, our bodies naturally revert to a catabolic process; it breaks down stored nutrients for use. (This is especially helpful during winter or whenever food was scarce.)

One recurring theme of nutrition is the natural ebb-and-flow between anabolic and catabolic states. We are not meant to eat all time; it is natural to go without food.

Macronutrients

There are three macronutrients, or “macros” for short: protein, carbohydrate, and fat.

Ham = protein
Rye bread = carbohydrate
Swiss cheese = fat

Of course, each of those foods contain a blend of macros—for example, Swiss cheese has both fat and protein—but for the sake of simplicity, we’ll just use each food as one macro.

Each macro is made up of a smaller unit.

Proteins are made up of amino acids.
Carbohydrates are made up of monosaccharides, with the main one being glucose. (More on this in a second.)
Fats are made up of fatty acids.

Let’s take a look at each.

Carbohydrate metabolism

Carbohydrates are made up of saccharides (from the Latin for “sugar”). A complex carbohydrate has more saccharides are called polysaccharides (Latin for “many sugar”).

First, we have monosaccharides (Latin for “one sugar”). The three are glucose, fructose, and galactose.

Oligosaccharides have some saccharides. The most frequent are disaccharides. Polysaccharides have even more (generally more than a dozen).

So what happens to our rye bread?

In the mouth, salivary amylases break down the polys into smaller units.
In the small intestine, pancreatic amylases break them down into maltose disaccharides.
The maltose is broken down by the enzyme maltase, which yields two units of glucose.
The glucose enters the body to be used for energy now, or to be stored for energy later as glycogen.

In addition, there are three types of polysaccharides:

Fiber (indigestible; contains cellulose)
Starch (exclusively glucose)
Sugar (aka “sucrose”; equal parts glucose and fructose)

Disaccharides are made from a blend of monosaccharides. See below:

Maltose = glucose + glucose
Sucrose = glucose + fructose
Lactose = galactose + glucose

Each disaccharide is hydrolyzed by a familiar-sounding enzyme. Thus, maltose is broken down by maltase, sucrose by sucrase, and lactose by lactase. Pretty simple, right?

Cellular respiration

The purpose of cellular respiration is to convert glucose—found predominantly in carbohydrates—into ATP.

But it’s not that simple.

You see, there are three parts to cellular respiration:

Glycolysis (also called the glycolytic pathway)
The Krebs Cycle (or Citric Acid Cycle)
Oxidative phosphorylation

Glycolysis

Let’s start with glycolysis. It literally means “The splitting of glucose.” Glycolysis happens in the cytoplasm and is anaerobic. This process breaks down glucose in three ways: glucose in the bloodstream, stored glycogen, and glycerol (which was broken from a triglyceride).

In a nutshell, glycolysis converts glucose to pyruvate.

Between glycolysis and the Krebs cycle lies the transition reaction. This is where the pyruvate from glycolysis is converted to acetyl-CoA, which is the starting point for the Krebs cycle.

Transition reaction = Pyruvate (3 carbons) → acetyl-CoA (2 carbons) + CO2 + NADH.

Remember that each glucose molecule contains six carbons; therefore, each glucose molecule produces two molecules of pyruvate, which is then converted into two acetyl-CoA, two CO2, and two NADH.

Glucose → 2 pyruvate → 2 acetyl-CoA + 2 CO2 + 2 NADH

Riveting, right?

Now, you may be wondering what NADH is. This is when NAD+—which acts as a hydrogen buffer—gains a hydrogen molecule and becomes NADH. (Hence the “H” in NADH.)

In order for glycolysis to continue, the NADH must give up its hydrogen. This is done in one of two ways: either the hydrogen is passed on to the Krebs cycle, or it is combined with pyruvate to form lactic acid. In either case, the NADH recycles back to NAD+ and glycolysis continues.

Keep in mind, however, that while glycolysis continues, it can only go so fast. It’s like a particular gear on a bicycle: no matter how hard you peddle, you can only go so fast before you need to switch gears. So, glycolysis hums along, producing 2 ATP with each cycle, but at some point, you’re going to need to switch gears.

That next gear is the Krebs cycle.

Krebs cycle

Now, let’s move on to the Krebs cycle (also known as the citric acid cycle). The pyruvate created during glycolysis turns into acetyl-CoA, which is the starting ingredient for the Krebs cycle.

The Krebs cycle consumes acetate (in the form of acetyl-CoA) and water, reduces NAD+ to NADH, and produces carbon dioxide.

Similar to glycolysis, the Krebs cycle produces 2 ATP. It also produces two other molecules called NADH and FADH2, which carry electron on to the next stage: oxidative phosphorylation.

Oxidative phosphorylation (aka the electron transport chain)

When it comes to ATP production, oxidative phosphorylation is the world champion.

How much ATP? As you recall, the Krebs cycle produces two ATP, same as glycolysis.

But the election transport chain? While the exact number differs, but it’s somewhere in the neighborhood of a whopping 32 ATP. That’s huge!

So, how does it work? Electrons from NADH and FADH2 are passed through the electron transport chain; as they move through they are oxidized (meaning they give up an electron) and, as a result, generate more ATP.

Admittedly, this is a grossly over-simplified explanation. You can spend weeks learning about cellular respiration if you wish (I’m not going to stop you), but understanding the basics is enough to help you with nutrition.

Key point: cellular respiration needs oxygen to create ATP. This means that aerobic exercise uses cellular respiration and anaerobic exercise doesn’t.

Protein metabolism

Protein is made up of amino acids. Chains of amino acids are called peptides or polypeptides.

There are a total of 20 different amino acids in our bodies. Of the 20 amino acids, 9 of them are essential. This means that we cannot produce them ourselves; we need to include them in our diet.

Amino acids serve dozens of functions. To remember the most important, use the acronym SHAMEN, which stands for:

Structure
Hormones
Antibodies
Messages
Enzymes
Neurotransmitters

In addition to the above, amino acids can also serve as metabolic fuel. Unlike carbs and fats, however, amino acids cannot be stored for later; they must be used now or converted into glucose or triglycerides for storage.

All amino acids have a similar structure. They contain a carboxyl group (COOH), an amine group (NH2), a central carbon, and a side chain (which is also called an R group). The side chain is what differentiates one amino acid from another.

So how are proteins metabolized?

First, amino acids have their amine group removed in a process called deamination. The liberated amine group eventually becomes ammonia.

This is all fine and dandy, but there’s a catch: ammonia is highly toxic. Breathing ammonia leads to an immediate burning of the eyes, nose, throat and respiratory tract and can result in blindness, lung damage or death. So it makes sense that our bodies don’t want a lot of this stuff floating around.

To neutralize the ammonia, your body adds carbon dioxide (CO2) to the amine group. This results in two molecules: water and urea, both of which are later excreted in urine.

Key point: ammonia is a natural byproduct of protein metabolism, and must be removed from body.

Once the amine group has been stripped, what remains is the carbon skeleton (also called α-keto acid, which is pronounced “alpha”). The carbon skeleton is used for either non-protein products (e.g. glucose via gluconeogenesis, which is Greek for “make new glucose”), recycled into another amino acid, or oxidized for energy.

When amino acids reach the liver, they have three potential fates. About 20% of amino acids and released into the bloodstream, another 20% are used by the liver to synthesize new proteins, and the remaining 60% are deaminated and used for either energy or further processing.

Although protein can be used for energy

Fat metabolism

Lipolysis (“breaking fat”) occurs when you break a triglyceride into a glycerol and its fatty acids.

Lipolysis = Triglyceride → Glycerol + Fatty acids

Triglycerides are how fats are stored in the body. They are made of one glycerol molecule and 1–3 fatty acids (called mono-, di-, or triglycerides, respectively). Think of glycerol like a trident, with each fatty acid resting on one its spears.

One interesting thing about triglycerides is that they can contain different types of fatty acids. So, for example, one triglyceride can contain one saturated fatty acid, one monounsaturated fatty acid, and one polyunsaturated fatty acid.

Triglycerides don’t enter our cells very well. Therefore, they are broken down through lipolysis so the glycerol and fatty acids can pass the plasma membranes and enter the cell. Once inside, they are put back together as triglycerides.

So how are triglycerides used for energy? Well, we’ve already discussed how lipolysis separates the glucose molecules from their glycerol backbone. Once this happens, the glycerol enters the glycolytic pathway—which is the same pathway for glucose (carbohydrate)—and the fatty acids are metabolized through a process called beta oxidation.

Beta oxidation is how your body converts fatty acids into acetyl-CoA.

Fatty acids are difficult to transport through the body. Unlike other nutrients—which are water soluble—fats don’t dissolve in water. As a result, too many free-flowing fats in the blood can be toxic. That’s why they are packaged as triglycerides and moved through the body via lipoproteins.

Lipoproteins

Lipoproteins, as their name suggests, are molecules made up of lipids (fats) and proteins that shuttle lipids (triglycerides and cholesterol) through the body. Think of lipoproteins as cab drivers, carrying their lipid passengers along.

There are many different types of lipoproteins, but they fall into two main categories:

LDL (low-density lipoprotein), sometimes called “bad” cholesterol, makes up most of your body’s cholesterol. High levels of LDL cholesterol raise your risk for heart disease and stroke.
HDL (high-density lipoprotein), or “good” cholesterol, absorbs cholesterol and carries it back to the liver. The liver then flushes it from the body. High levels of HDL cholesterol can lower your risk for heart disease and stroke.

In a nutshell, you want low LDL levels and high HDL levels in your panel. (But, as you’ll soon see, it’s more nuanced than “LDL = bad; HDL = good”.)

There are in fact two types of LDL (which are not separated in your standard blood panel): large, buoyant LDL, and small, dense LDL. The large, buoyant LDL poses no threat; the small, dense, LDL, however, are something to watch out for.

Why? Because small, dense LDL particles are the most likely to get trapped in your arterial walls. And due to the fact they stay in the bloodstream longer than their large, buoyant counterparts, these small, dense LDL are also most likely to become oxidized—which is responsible for the progression of atherosclerosis and cardiovascular disease. Put simply: too many small, dense LDLs are very dangerous.

But you may be wondering: what affects a lipoprotein’s density? The answer is the ratio of fat and protein molecules within the lipoprotein. Proteins are more dense than fats. Therefore, HDL—the highest-density lipoprotein—has the least amount of triglycerides and cholesterol, while VLDL—which stands for very-low-density lipoprotein—has the most.

Key point: HDL is more dense because it has more proteins than fats. LDL is less dense because it has more cholesterol and triglycerides.

When looking at your blood work, focus on your LDL particle count (LDL-P), rather than its concentration (LDL-C). The following analogy will help.

Picture two roads. Both have 100 passengers. The first road has 5 buses, each carrying 20 people. The second road, however, has 100 cars with one person each. Which is more congested? The second freeway, obviously.

In the above, the passengers represent your LDL-C (concentration), and the vehicles represent your LDL-P (particle count). As you can see, both roads have the same LDL-C; that is, they’re the same concentration. But their particle count is very different.

Unfortunately, most lipid panels only do LDL-C—which doesn’t give a clear picture of your cholesterol.In other words, your standard blood panel doesn’t count the number of vehicles. It just looks at the passengers. So your total cholesterol is meaningless. (That may sound like a strong statement, but it’s backed by many leading lipidologists.)

So, what does all this mean? What should we look for—and worry about—when looking at our blood panels?

Both triglycerides and LDL are indicative of heart attacks. But triglycerides are much, much more dangerous. According to Dr. Robert Lustig, people with high LDL are 30% more likely to have a heart attack in their lifetime. Triglycerides are even worse at 80%. Therefore, you should be aware of both.

But remember: numbers aren’t meant to be taken in isolation. Look at the ratios of triglycerides to HDL-C. Ideally they’re are 1:1. If, however, you have more triglycerides than HDL-C, you could have a problem.

Another useful ratio is your total cholesterol divided by your HDL. Anything under 3.5 is considered OK.

Lastly, take a look at your ApoB levels. There is one ApoB for every LDL particle in your body; this 1:1 ratio gives you an accurate picture of your LDL particle count. You’ll be shocked to learn, however, that ApoB is also not included in standard blood panels.

So, in conclusion, you’ll want to focus on increasing your HDL, while decreasing your triglycerides and LDL particles (which include ApoB).

But how?

How to improve your cholesterol levels

As we’ve reviewed above, your goals should be to:

Increase HDL
Decrease LDL (in particular the small, dense LDL particles)
Decrease ApoB
Decrease triglycerides

Fortunately, many activities help improve all your cholesterol numbers simultaneously. For instance, exercise will increase HDL while lowering triglycerides and LDL.

There are a few exceptions, however. Let’s look at the best ways to get your blood cholesterol where you want it.

Quit smoking. Smoking has been shown to decrease HDL, increase LDL (as well as their “stickiness” and therefore more likely to oxidize), narrow your arteries, and thicken your blood (which can lead to overclotting). Smoking also contains a compound called acrolein, which prevents HDL particles from transporting LDL back to the liver for elimination. Oh, as a cherry on top, it also increases your chance of heart attacks and strokes.

Eat more soluble fiber. While both kinds of fiber are important, soluble fiber is key to reducing LDL cholesterol. Here’s why: as soluble fiber—which dissolves in water—flows through your bloodstream, it binds to bile salts. (As you may recall, bile salts contribute to emulsifying fats in the diet, which helps the body digest them properly.) Since bile salts are made of cholesterol, your body uses cholesterol to replace the bile salts that soluble fiber has removed. The result? Lower cholesterol. Foods high in soluble fiber include legumes, oats, barley

Eat more beta glucan (β-glucan). We’ve already mentioned soluble fiber above, but this specific type of soluble fiber deserves special mention. A meta analysis concluded that eating 3 grams/day of beta glucan—which is found in oats, barley, some mushrooms, seaweed, rye and wheat bread—is enough to reduce cholesterol. To get 3 grams, you’d need 1.5 cups of cooked (or 3/4 cup uncooked) oatmeal or barley.

Increase omega-3 fatty acids. Omega-3 fatty acids—which are mainly found in fish and sea plants like algae and seaweed—have been to shown to reduce total cholesterol, non-HDL cholesterol, triglyceride (TG) levels, and the total cholesterol/HDL ratio. The linked study showed improvements for eating fish vs fish-oil supplements; while both worked, those who ate fish twice a week showed the biggest improvement in blood lipids. Strangely, the group who took fish-oil supplements actually saw a small increase in LDL. But their overall ratios significantly improved.)

Reduce saturated fat (particularly dairy).

**Drink alcohol moderately (or not at all). **Studies have shown moderate alcohol can increase HDL, but only to a small degree.

Exercise.

Blood work: what to ask for (that your doctor wouldn’t normally provide)

Ask for the following:

LDL-P
ApoB

Hormones and neurotransmitters in the digestive system—in order of appearance

I couldn’t find an order of which hormones and neurotransmitters occur where and when in the digestive process, so I pieced the following together myself. (This may or may not be correct.)

Ghrelin is a hunger hormone that is released when you’re not eating enough. It stimulates appetite and the release of growth hormone.
Gastrin (stomach). Produces gastric juice. Protein-rich foods tend to stimulate the most gastrin release.
When hydrocholoric acid and pepsinogen are released in the stomach, several things happen: the lower esophageal sphincter closes, peristalsis increases, the gallbladder contracts (to send bile to the small intestine), and the pancreas releases bicarbonate.
Secretin (small intestine). Calls for bile and bicarbonate to neutralize acid. It inhibits gastrin. Released in response to hydrochloric acid.
Cholecystokinin (CCK) asks the gallbladder to contract and release bile for emulsification of fats. It is released at the same time as secretin. Released in response to fat.
Motilin (small intestine). Released when bicarbonate is dumped into the small intestine to neutralize stomach acid.
Vasoactive intestinal peptide (VIP) slows down stomach activity while stimulating intestinal activity.
Gastric inhibitory peptide (GIP). Small intestine. Decreases stomach churning to slow the stomach from emptying; stimulates insulin release; reduces gastric and intestinal motility; increases fluid and electrolyte secretion.
Serotonin increases small intestinal motility and decreases the production of stomach acid.
Once food (primarily fat) hits the end of the small intestine, neurotensin relaxes the lower esophageal sphincter, stops the production of stomach acid and peptin, and regulates motility. In other words, it closes up shop.
Somatostatin: a hormone that inhibits the secretion of hormones—including glucagon, insulin, and gastrin.
Peptide YY is released hours after eating. It inhibits stomach motility and tells the colon to absorb water and electrolytes (sodium and potassium).
Acetylcholine is a “rest and digest” neurotransmitter that uses muscle contractions to move food through the GI.
Overall, it takes about 4–8 hours for chyme to travel through the small intestine. It takes 12–25 hours to travel through the colon (large intestine) and out the anus.
Useful video: https://www.youtube.com/watch?v=XANFAdMFkYY&ab_channel=AnatomyAcademy
Wikipedia https://en.wikipedia.org/wiki/Gastrointestinal_hormone

Below is a table that summarizes the hormones and neurotransmitters.

Glucagon and epinephrine both break down stored glycogen (a process called glycogenolysis)

A table of hormones (and enzymes) and how they affect each other

Hormones, like people, can turn each other on.

Or off.

For example, insulin down-regulates growth hormone while up-regulating glycogen synthase.

Because of these relationships, I find it useful to think of hormones as “switches” that can be turned on or off. These switches are affected by other hormones.

Below is a table summarizing the relationships between hormones.

Ketosis for smart people

Although the “keto diet” has become popular, it’s not widely understood by most people.

In short, the purpose of a keto “diet”—and I loathe to call it a diet—is to restrict carbohydrate intake below ~50g/day. Once below this level, your body begins to produce ketone bodies and you’re said to be in ketosis.

I certainly enjoy being in ketosis. I began experimenting with it in 2016 while training for a 50-mile ultramarathon. Ketosis’s appeal for long-distance runners is simple: by reducing carbs, you increase ketones, and can run farther without running out of glucose. While training for the ultra, I routinely ran trail marathons in a fasted state.

Ketosis is a metabolic state. It is a not a diet based on particular macros. Why? Because there are many ways to get into ketosis. For example:

Fasting
Salads
Carnivore

Not sure if this is correct (from Gundry/Tom podcast) 30% of calories in goat and sheep cheese is MCT. (Cows do not produce MCT.) This helps uncouple mitochondria—meaning the mitochondria produces heat rather than ATP, which can be a sign of metabolic flexibility and longevity. This may be a contributing factor in the Blue Zones, where many people are sheep and goat herders.

What happens if you don’t eat carbs?

Your body adapts. Here’s how: Your body converts fatty acids into acetyl-CoA via process called beta oxidation. During beta oxidation, two carbons are sliced off the end of a long fatty acid. These carbons become acetyl-CoA.

Beta oxidation is all fine and dandy, mind you, but it creates a problem: the acetyl-CoA begins to build up. (Nerd alert: this is because there isn’t enough oxaloacetate to move the acetyl-CoA to the Krebs cycle.) As the acetyl-CoA builds up, your liver—that glorious superhero of the digestive system—converts the acetyl-CoA into ketone bodies.

Key point: The fatty acid synthase system adds two carbon units to a fatty acid chain. Beta oxidation removes two carbon units.

Resistant starch

Resistant starch isn’t digested by humans, but it plays an important role in health. When these starches reach the colon, they provide food for bacteria, who convert the starch into short chain fatty acids (SCFAs). These SCFAs are either absorbed by our bodies or used to feed our bacteria. (This is a good thing!)
Speaking of good things, here are the benefits of SCFAs in the colon
- Benefit
Long story short: if you eat enough resistant starch, you have enough SCFAs—which leads to improved health.
Bob’s Red Mill Potato Starch is an easy way to get more resistant starch. 1 tablespoon = 8 grams of resistant starch. Remember: you must eat it cold! Resistant starch breaks down when heated (but you can always chill it after cooking). For example, you can cook potatoes or rice, then cool them in the fridge before eating.
Green bananas are also a great source of resistant starch. While they taste gummy on their own, you can blend them in a smoothie.
If you’re in ketosis, don’t fret: since resistant starch is not raise blood sugar levels, it will not kick you out of ketosis.

Position stands—a short-cut to find reputable, evidence-based advice from leading experts

Search for “position stands” from reputable organizations. You’ll get a brief summary of their stand on a wide variety of issues. This is really helpful for getting a high-level view of a subject. For example, here’s the International Society of Sports Nutrition position stand on protein intake on exercise. And here’s a list of all the position stands from the ACSM. (You can search online for any organization’s position stands pretty easily.)

How to build muscle

You must be in a caloric surplus
Eat up to 1g/lb protein bodyweight
Train every body part twice a week
Get at least 10–20 sets per week per body part
5 reps at heavy will get you as strong as 10–12 reps at moderate and 20 reps with light. This assumes you train close to failure. (1–2 reps shy of failure.) Variety is good, but the bulk of your training should be between 8–15 reps. This is the sweet spot that allows you to get more reps in without too much fatigue.
Rest between 90 seconds and three minutes.

A list of foods high in fiber (and relatively low in carbs)

What will will likely kill you—and how to avoid it

Below is a list of what kills the most people in the U.S. (and likely most developed nations):

Cancer
Cardiovascular disease

Hydration

Aim for 500mL of water 30 minutes before exercising, and 250mL for every 15 minutes of exercise. Sure, this is all well and good, but I used to run trail marathons in a fasted state with no water and felt fine. Then again, I was probably being dumb.

Over-hydration can be a problem. In his book Natural Born Heroes, Chris McDougall points out that while long-distance runners die occasionally from over-hydrating, no one ever died from dehydration.

My take? Drink a bit more than you think you need ahead of time. Then sip occasionally.

Supplements

Protein supplements. Be sure to look for ones that are NSF Certified for Sport. Here’s a link.

A 20-minute walk after eating will reduce your post-prandial glycemia by up to 30%. To put that into perspective, that’s twice as effective as metformin, the most widely prescribed medicine for blood sugar control.

🪴 Quartz 4.0

Explorer