Supporting the Immune System - Macronutrients

In the previous article we discussed the various ways the ketogenic diet might be beneficial to the immune system. We found that it has the potential to improve inflammatory status, decrease fat mass, promote stable blood sugar, and improve immune cell function. However, as noted in that article, the ketogenic diet is simply defined by a specific ratio of macronutrients (high fat, low carb). That means that one person can eat a bunch of low-quality processed food (like pepperoni and sausage), and another can eat a bunch of high-quality healthy food (like wild-caught salmon and broccoli) and both could be considered Keto. 

This discrepancy can lead to HUGE differences in the consumption of protein, fat, vitamins and minerals, phytonutrients, and fiber, which all play very important roles in immune function. 

In this article, we’ll take a look at the role macronutrients specifically play in the immune system, and what to choose when it comes to protein, fat, and carbohydrates for optimum health and immune function. 

Protein: The most important macronutrient for immune health

Although I would guess that most keto dieters are in no danger of being protein deficient, as Keto tends to be a meat-centric diet for most people, it is still the most important macronutrient for immune health. Adequate intake of high-quality protein is vital to immune function, and if you’re not a meat-eater, it’s important to take special care in making quality protein decisions.

What is Protein and Why is it Important?

Protein is a macronutrient, which means you need it in large quantities. This makes a lot of sense because most things in your body are made up of protein. In fact, protein is an essential component of all body tissues. 

Your body builds many different proteins to serve many different functions. Among other things, protein:

• Repairs damaged tissue
• Catalyzes life-generating chemical reactions 
• Digests food 
• Carries nutrients throughout the body
• Acts as a messenger
• Balances fluids
• Acts as a receptor on cell surfaces
• Builds, repairs, and is a part of cell membranes
• and so much more

Many of these functions are important for the immune system. 

Protein is made up of smaller units called amino acids. To put it another way, amino acids are the building blocks of protein. To make a protein, amino acids are strung together kind of like pearls on a pearl necklace. Some amino acids your body can make on its own. Others you have to get from the food you eat. The amino acids that you must get from food are called essential amino acids. Foods that contain an adequate amount of all the essential amino acids are considered complete proteins. 

In order for your body to produce the proteins it needs for optimal immune function, it needs plenty of the raw material (amino acids) to build them. There are 20 unique amino acids used by the human body. Nine of them are considered essential. In other words, you have to eat food sources of protein that contain the essential amino acids. Once eaten, your digestive system disassembles the protein into all the individual amino acids. This process is kind of like clipping the string of pearls so that you are left with the individual pearls. The individual amino acids are then absorbed into your body. Now your body can reassemble the pearls to create different types of pearl necklaces (protein) to meet its current needs. 

To illustrate, let’s say you eat a chicken breast. Chicken breast is predominantly muscle tissue, which is mostly made of protein. Chicken meat is a complete protein, and therefore contains adequate amounts of the essential amino acids. Your digestive system breaks down the protein into its individual amino acids, your small intestine absorbs those amino acids into your body, then your body reassembles those amino acids in unique ways to build whatever proteins it needs. It’s kind of like taking a box of Lego and building the Death Star or a castle. 

Protein and the Immune System

Poor protein status can result in poor thymus function[*]. The thymus is an organ that operates like a boot camp. It trains specialized immune cells, called T-cells. These cells play a vital role in orchestrating the immune response to kill invading cells, infected body cells, and cancer cells.  

Additionally, there are very important immune components that are made out of protein, such as complement components and cytokines. The complement system is made up of a bunch of proteins that kill invading cells and initiate an immune response. Cytokines are proteins that the immune cells use to communicate with each other to coordinate the immune response. 

Think about it. If you haven’t been eating enough protein and your body is a little low on some essential amino acids, your immune system may not have the building blocks it needs to produce complement proteins, cytokines, and T-cells. That would leave your military understaffed and without the resources it needs to effectively organize an attack or recognize and kill the enemy. Thus, you are more vulnerable to invasion and defeat.  

Therefore, it should be no surprise that protein deficiency increases the risk of serious infections, impairs wound healing, and leads to a wide range of disorders that can impact every system of the body[*].

So, How Much Protein Do You Need?

Exactly how much protein you need as an individual isn’t an exact science. There are many factors that come into play, including health status, activity level, body composition, personal goals, genetics, and other factors known and unknown. However, general guidelines have been proposed based on the available evidence. 

There are two ways you can look at protein goals; overall daily intake in grams (RDA), or as a percent of calories (AMDR).

Recommended Daily Allowance (RDA)

The Institute of Medicine (now known as the National Academy of Medicine) set the recommended daily allowance (RDA) of protein at 0.8 g/kg per day. This should be looked at as the minimum amount of protein you should consume each day for most healthy people. The idea is that this is how much protein you need to prevent muscle loss in the context of maintaining body weight. 

To calculate RDA:

• Step 1) Body weight in lbs. x 0.453 kg/lbs. = body weight in kg
• Step 2) Body weight in kg x 0.8 g/kg = your protein RDA  

However, this method will pump out a number that is probably significantly lower than what you generally consume. Most Americans consume double the RDA at around 1.6 g/kg per day[*], and research suggests that there are benefits to consuming protein higher than the RDA. 

Some benefits include improved[*]:

• Maintenance of and building muscle mass
• Strength and physical function
• Inflammatory status
• Weight loss 
• Cardiovascular disease risk markers
• Insulin sensitivity 
• Bone health

Acceptable Macronutrient Distribution Range (AMDR)

Another way to look at protein requirements is as a percentage of total daily calories. This is how the AMDR is presented. In this model, daily protein intake is recommended to be within 10-35% of daily calories. On average, this works out to be 1.05 – 3.67 g/kg[*]. This is a large range, which allows for individual factors. 

No adverse effects have been shown from consuming protein higher than the RDA, but within the AMDR. On the contrary, only benefits have been observed, as listed above. The primary exception is people with renal failure or genetic disorders who cannot process protein effectively. These individuals have special protein requirements.   

On the Ketogenic Diet, you will need 20-25% of your calories to come from protein. 

Typically, this will convert to around 1.0-2.0g/kg. 

Best Sources of Protein for Immune Health

To provide your body, and your immune system with the best resources, you should strive to consume most of your daily protein from high-quality protein sources. High-quality sources provide the right proportion of essential amino acids (building blocks) and are easily digestible, so that the goods actually get to where they need to go.   

Below is a great infographic presenting high-quality sources of protein. A score of 0.8 and above is considered “good”, while a score of 1.0 and above is considered “excellent”. Sources that are “good” or “excellent” are almost entirely animal products. If you are a vegetarian, you just need to be more cognizant of your protein sources and be sure to get a wide variety. 

Fat

Fat plays a complicated and poorly understood role in immune function. Everything about fat is complicated — from the way it is categorized to the varying effects it has on the human body and health. In this section, I’ll attempt to provide you with a good foundation to navigate the world of fat, then discuss what we know about how the different types of fat affect the immune system. 

Understanding Fat

It might be helpful to start with a basic explanation of some key words that are often thrown around in association with fat. 

Some fat-related key terms we often hear include: 

• Fatty acids (FA)
• Saturated fatty acids (SFA) and unsaturated fatty acids (UFA)
• Monounsaturated fatty acids (MUFAs)
• Polyunsaturated fatty acids (PUFAs)
• Triglycerides (TG)
• Short-chain (SFA), medium-chain MCFA), long-chain (LCFA) fatty acids 
• Omega-6s and Omega-3s 
• DHA and EPA
• Trans fat

FAs, SFAs, UFAs, MUFAs, PUFAs, and TG

The term fat collectively refers to a group of chemical compounds called fatty acids (FAs). Fatty acids (FA) are basically a string of carbon atoms bound to a bunch of hydrogens and some oxygen in a configuration that makes it acidic. You need some in-depth knowledge of chemistry to understand what that means, but just recognize that the term acid doesn’t necessarily mean a chemical that is going to melt your skin off. 

The reason I bring up the chemical structure is because it will help you understand the terminology. When all the carbons in the fat are totally saturated with hydrogens, then it is called a saturated fatty acid (SFA). Saturation makes the fat very stable, resistant to air and higher temperatures, and solid at room temperature. When one or more of the carbons in the carbon string are not saturated with hydrogen, then the fat is called an unsaturated fatty acid (UFA). 

Any carbon that is not saturated with hydrogens forms a double bond with the next carbon in the chain. Unsaturated fatty acids are further categorized based on how many carbons are unsaturated and how many double bonds are present. When one carbon in the string is NOT saturated, it is called a monounsaturated fatty acid (MUFA). When 2 or more carbons are unsaturated, then it’s called a polyunsaturated fatty acid (MUFA). 

The lack of saturation in these fats changes their quality. They are fluid at room temperature, and they are more susceptible to rancidity by air and heat. They also are used differently by the body and have different health effects.

In adipose tissue, fats are stored as triglycerides (TG), AKA triacylglycerols (TAG). The chemical structure of a TG consists of a glycerol backbone with three fatty acids attached to it (see image below). Typically, when we eat fatty acids in our food, they are attached to a glycerol molecule forming a TG (As a side note, the glycerol component can be used in gluconeogenesis (GNG) when the body is low on glucose and needs to make it from other materials). The fatty acids attached to the glycerol backbone can be any kind of SFA or UFA. All 3 FAs attached to the glycerol can be the same, or they can be any combination of 3 different FAs, as illustrated below. 

SCFA, MCFA/MCT, LCFA

Saturated fatty acids can be further categorized into short-chain, medium-chain, and long-chain based on the respective length of the carbon chain. Short-chain fatty acids (SFA) are produced by some types of bacteria in the gut microbiome as a byproduct of digesting fiber and provide a host of metabolic benefits[*]. You may be familiar with medium-chain fatty acids (MCFA), also referred to as medium-chain triglycerides (MCT), as a quick and easily digestible form of fat popular in Keto circles. Long-chain fatty acids (LCFAs) are typically found in the fat of land animals and take longer to absorb than SCFAs and MCFAs.  

Omega-6, Omega-3, DHA, EPA

MUFAs and PUFAs only occur in long chains. MUFAs are commonly present in plant, nut, and seed oils, such as olive oil, avocado oil, and almond oil. They have one unsaturated, double-bonded carbon that is typically in the 9th position, making them omega-9 fatty acids. 

PUFAs can be further categorized into Omega-6 and Omega-3. Omega-6 FAs are a group of PUFAs that have the final unsaturated carbon in the 6th position of the chain. These fats are typically found in vegetable oils, nuts, seeds, and land animals. Omega-3 FAs are a group of PUFAs that have the final unsaturated carbon in the 3rd position of the carbon chain. Omega-3s are found in the highest quantities in fatty fish in the form of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). These two omega-3 FAs are very important for fetal development, as well as nervous system and immune system function. Omega-3s are also found in nuts and seeds, such as walnuts, flaxseeds, and chia seeds and are commonly in the form of alpha linolenic acid (ALA). It’s notable that DHA and EPA can be produced from ALA, but the process is inefficient. This is why health recommendations typically include regular consumption of fatty fish.  

Trans fat

We’ve all heard of the dreaded trans fat! It was big news in the first decade or so of the 2000s because a preponderance of evidence began to confirm that trans fat consumption significantly increases the risk of heart disease. Oops! It was frequently used in processed foods because it was cheaper than other fats and increased product shelf-life. It was even thought to be healthier than saturated fat, despite early research in the 1970s and 1980s suggesting otherwise[*]. 

While trans fat does occur naturally in small amounts, most of the trans fat being consumed is artificially produced in the form of partially hydrogenated oils. Partial hydrogenation is the process of blasting unsaturated fats with hydrogen ions to make them more saturated. Most often, double bonds in UFAs occur in a cis configuration. However, the process of partial hydrogenation creates double bonds in a trans configuration, which changes the properties of the fat. See this video for more details. 

Trans fats increase LDL (“bad”) cholesterol, while decreasing HDL (“good”) cholesterol. This increases the risk of heart disease. The use of trans fat in American products has been severely limited by the FDA since 2015. However, food manufacturing companies have been given a grace period to reformulate their products, and the strict changes regarding trans fat may not be fully implemented across the board just yet[*]. 

Even so, there are still some tricky ways that food companies can sneak trans fat into your food. Products are allowed to claim that they contain 0g of trans fat on nutrition labels if they contain less than 0.5g per serving. However, what determines a serving is up to the company. The company can be tricky and deliberately choose a serving size that contains less than 0.5g of trans fat even though in reality you’ll eat a lot more than that amount in one sitting[*]. 

For this reason, you should always look for the term partially hydrogenated oil in the ingredients list of packaged foods. Trans fats are not “generally recognized as safe” by the FDA and should be avoided as much as possible[*]. 

This is all I’ll say about trans fats. Most of us know they are not good, and if you are eating Keto, then you shouldn’t be eating the types of foods that tend to have trans fats anyway. 

I hope the above breakdown demystifies fat a little bit and provides some background for the next section. For a more in-depth review of the gory details, see this paper -OR- watch this video.

Fat and the Immune System

Fats also play a major role in regulating the immune system. Fats become embedded in the cell membranes of immune cells, they modulate gene expression of immune cells, and are used to make various factors that control the immune response[*]. However, each type of fat has different immune-regulating properties, and too much or too little of some types of fat may lead to immune dysfunction. Read on for all the details about which fats to include more of, and which to limit for healthy immune function.  

SFA

Saturated fatty acids (SFA) are found mostly in land animal foods, including meat, poultry, dairy, butter, and eggs. There are also some plant sources, such as coconut oil and palm oil, which have become very popular in recent years. 

The overall picture for SFAs does not look great for the immune system. In general, SFAs appear to upregulate pro-inflammatory conditions which could result in an exaggerated immune response or systemic chronic inflammation[*]. As noted elsewhere, this can be detrimental to one’s health. It could cause or perpetuate conditions like rheumatoid arthritis, diabetes, chronic pain, Alzheimer’s disease, heart disease, and others. Additionally, systemic chronic inflammation can make you more susceptible to severe infections[*].  

On the other hand, SFAs are a component of some highly nutritious foods! For example, eggs, coconut, whole milk, and grass-fed beef are far more than just saturated fat! They deliver other nutrients such as high-quality protein and immune-boosting vitamins and minerals. 

In the case of SFAs, it may be better to think about them within the context that they are delivered. For example, foods high in SFAs that should be limited or avoided altogether include French fries, chips, bacon, sausage, pastries, pies, and other highly processed and fried foods. These foods are nutrient-poor and/or high in processed ingredients and additives, which at best is unsupportive of your immune system, and at worst detrimental to your immune system. Many of these foods you cannot eat on Keto anyway. The ones you can eat on Keto, such as bacon and sausage, should be enjoyed happily, but in moderation.

The 8th edition of the dietary guidelines for Americans recommends reducing SFA intake to less than 10% of total calories[*]. On a 2000 calorie diet, that is 200 calories, or about 22 grams per day (200calories/9 calories/g = 22.22g).

This limitation is based on data that links saturated fat consumption to increased LDL (bad cholesterol), and elevated LDL to increased risk for heart disease. On Keto, most people exceed the less than 10%/day recommendation. However, research suggests that many people on Keto actually have decreased LDL levels, as well as improvements in other risk factors for heart disease, despite likely consuming more than 10% of their calories from saturated fat[*][*][*]. 

On the other hand, in research that compares different ketogenic eating patterns, higher consumption of omega-3 fats tends to demonstrate the best response in lipid profile and inflammatory markers[*][*]. This suggests heart protection, as well as better immune function.

Therefore, it’s likely ok to get higher amounts of SFA in the context of a healthy ketogenic diet pattern rather than a carb-based diet. However, for best results, it must be recommended to get more of your fats from MUFAs and PUFAs and be sure to include high amounts of non-starchy veggies into your diet plan.

And if high cholesterol is something you struggle with, it would be prudent to monitor your lipids throughout your Keto journey.

MUFAs

Most of the research investigating the effect of MUFAs on the immune system looks at extra virgin olive oil (EVOO). This research is largely positive, suggesting that MUFA consumption regulates the immune system by suppressing pro-inflammatory molecules without impairing immune response to infection[*][*][*]. 

Therefore, regular use of olive oil in place of SFA may reduce severity of an infection such as COVID by reducing the overactive immune response, AKA “cytokine storm”, characteristic of severe COVID infections. 

EVOO is credited for improving blood pressure and cholesterol, while decreasing systemic chronic inflammation, risk of heart disease, neurological disease, diabetes, obesity, and others[*].  

You can find MUFAs in many great Keto-friendly foods, such as olives, olive oil, nuts, seeds, and the staple Keto-friendly fruit, avocado, and avocado oil. 

Canola oil is another great source of MUFAs, though widely chastised in Health Warrior and Keto circles. The hatred of this oil is largely unfounded in the research thus far. The main concerns are that most canola oil is from GMO crops, they are heated to high temperatures and contain small amounts of hexane, and contain small amounts of trans-fats. 

Thus far, research has not revealed any concrete health concerns associated with canola oil consumption. In fact, the research has been largely positive showing improved lipid profile[*][*] and decreased inflammatory markers[*]. 

However, if you are concerned about potential adverse health effects from canola oil, no problem! You can simply use EVOO or avocado oil to get your MUFAs.

PUFAs

Omega-6

You’ll find omega-6 fats in foods like walnuts, peanut butter, and many common cooking oils, such as safflower, sunflower, corn, cottonseed, and soybean oils.  

It’s long been hypothesized that omega-6 fatty acids are bad for our health. After all, these FAs provide precursors for pro-inflammatory molecules. The idea is that high intake of omega-6 FAs results in high production of pro-inflammatory molecules and causes systemic chronic inflammation (SCI). As mentioned multiple times, SCI is linked to most chronic diseases and impaired resistance to infection[*]. 

However, this hypothesis has not panned out as expected when put to the test. Multiple studies in humans have shown that higher intake of omega-6 fatty acids via supplementation does not lead to higher levels of inflammatory markers, such CRP, IL-6, IL-10, TNF-alpha, and others[*]. In fact, it turns out that omega-6 fats promote both inflammatory and anti-inflammatory mechanisms. Perhaps these mechanisms are only activated as needed, rather than simply based on amount of omega-6 consumed. 

On the other hand, high omega-6 consumption, while not directly inflammatory, can block the anti-inflammatory and inflammation resolving mechanisms of omega-3 FAs[*]. These two PUFAs compete for the same metabolic enzymes, and their products compete for the same receptors. 

It is thought that the ideal ratio between omega-6 and omega-3 is 1:1. This is difficult to achieve and may not be necessary to benefits. For example. a ratio of 2-3:1 decreased inflammation in patients with rheumatoid arthritis[*]. 

Omega-6 FA are more widely available in the American diet than omega-3s. In fact, it’s estimated that the average American consumes a ratio closer to 15:1[*]. Therefore, it’s important to consciously add sources of omega-3s into your regular diet, while decreasing the highest sources of omega-6, as seen in the chart below. 

Omega-3

The best sources of omega-3 fatty acids come from wild-caught fatty fish, like cod, mackerel, and salmon. You can also get omega-3s from flax seeds, chia seeds, walnuts, and omega-3 enriched eggs.

It is widely recognized that omega-3 fatty acids are anti-inflammatory. Omega-3 fats exert their anti-inflammatory mechanisms by inhibiting the activity of pro-inflammatory cells, increasing anti-inflammatory communication, and producing molecules responsible for resolving the inflammatory response, aptly named resolvins[*]. Omega-3s also improve the phagocytic activity of cells so they can destroy the enemy more effectively[*].

Interestingly, the omega-3 FAs DHA and EPA have demonstrated inhibition of the NLRP3 inflammasome. This is the same receptor involved in severe cases of COVID-19[*][*].You can find DHA and EPA in supplemental form or get them by eating fatty fish a few times a week. 

Carbohydrates

The primary role of carbohydrates in the immune system is to provide energy. Additionally, carbohydrates serve as building blocks for some molecules important for immune function.

One good example is that glucose is combined with protein to build a molecule called a glycoprotein that is part of the major histocompatability complex (MHC). These glycoproteins are embedded on the surface of your cells and help immune cells recognize your body cells vs. invading cells. This is kind of like presenting a flag on your ship to let the battleships in the area know that you are on the same team, so they don’t try to blast cannons through you when they see you coming. 

UH OH! What If I’m on the Keto Diet? Will I get Enough Carbs to Support My Immune System?

So far, I have yet to find any evidence that a low carb diet impairs immune function. Remember, the first role of carbohydrates in immune function is to provide energy. When on the ketogenic diet, your energy is coming from fat, so this role is covered as long as you are consuming adequate calories. Since you are using fat for energy, the small amount of carbohydrates you are consuming can be used for the few cells that cannot use fat for energy, and also to build molecules, like the MHC molecules mentioned above. Lastly, even if you don’t get enough carbohydrates, your body has other ways to generate the glucose it needs when dietary glucose is inadequate. This is the process known as gluconeogenesis (translated: gluco=glucose, neo=new genesis=create).

Carbohydrates and Inflammation

The most important point about carbohydrates, whether you are on Keto or not, is that you should be smart about your carb choices or else your immune function may suffer.

If you’re on Keto, you are basically restricted to non-starchy vegetables and a few low-carb fruits, which is excellent… if you actually eat them! 

If you are on a carb-based diet, then you should focus on complex carbohydrates from fruits, vegetables, beans, legumes, and whole grains. These foods tend to be rich in micronutrients, phytochemicals, fiber, and healthy fats, all of which support the immune system.  

Other carb sources include sugary drinks, candy, cakes, crackers, white rice, white bread, etc. These food-like substances (thank you Michael Pollan for this wonderful term) are composed primarily of processed, simple sugars and they lack nutrient density. When you eat these foods, they absorb quickly, spike your blood sugar, and spike your insulin. This can result in inflammation and impaired immune function as discussed in more depth in the previous immune system article. 

The Takeaway:

• Macronutrients are nutrients you need in large quantities
• Eat high-quality sources of protein such as fish, grass-fed beef, and eggs to provide your immune system with the raw materials needed to produce immune cells and make them function optimally
• Saturated fats come in highly nutritious packages, such as meat and dairy, but too much may cause immune dysregulation by exaggerating the inflammatory response
• Enjoy cooking with butter, but make an effort to use more olive oil and avocado oil to increase MUFA consumption and keep chronic inflammation low
• Eat fish 2-3 times per week for high-quality omega-3s to support appropriate immune response. For guidance on fish consumption click here.
• Get your carbs from a wide variety of low-carb vegetables every day for nutrients and fiber needed to keep the immune system healthy and strong.