In these uncertain times, in the face of a global pandemic, you may be wondering what you can do to protect yourself and your family from infection. Maybe you want to go above and beyond social distancing, wearing a mask, and washing the flesh from your hands. Maybe you are wondering if there are particular supplements, foods, or tinctures you should be taking to boost your immune system to fight infection. Maybe you are like me, and you want information free of hyperbole, bias, and exaggeration!
In the wake of the novel coronavirus, all of us here at Carb Manager want to provide you with just that!
Hi, my name is Tony O’Neill. I am a registered dietitian nutritionist (RDN) and Doctor of Physical Therapy (DPT), and I am Carb Manager’s staff nutritionist. In this series of articles, I will explore from a scientific perspective what each of us can do to support our immune systems in these trying times - without hyperbole, without exaggeration, and without trying to sell you something.
You have Carb Manager’s and my personal commitment to provide all of this information from a scientific perspective with supporting evidence. You’ll find links to references throughout these articles so that you may verify the information and track the logic. We commit to refraining from hyperbole and sensationalizing. This information is provided with our most genuine sincerity and desire to share real health and nutrition information, not with the intention of selling you a product or seducing you into clicking a link, i.e. clickbait.
In this first article, I’ll start with a brief overview of the immune system, and then dig into how the Ketogenic Diet might impact your immune health. In future articles, I will explore nutrition considerations that are important no matter what diet you choose, what supplements are worth taking, lifestyle habits that keep you healthy, and other factors that impact immune health.
So, let’s start at the beginning.
The Immune System - Your Body’s Military
We are all familiar with the basic concept of the immune system. The immune system can be likened to the military of your body. It prevents invading organisms (pathogens) from getting in and messing up the intricate workings of your inner self. Your skin and the linings of your gastrointestinal system and respiratory system are armed with various mechanisms to keep the bad guys out. When the bad guys manage to get in, they are met with aggression as your military immediately ramps up an attack to abolish the enemy. This is the innate immune system and this defense is called the inflammatory response.
Your immune system also takes notes. When it encounters a new enemy, it develops more effective ways to kill it. It also puts up wanted signs - IF YOU SEE THIS ORGANISM, DESTROY IMMEDIATELY. The next time the enemy shows up, your immune cells recognize it quicker and destroy it faster and more effectively. This is the adaptive immune system and by taking advantage of its adaptive qualities, we can design vaccines that train our troops to kill specific enemies.
The inner workings of the immune system are very intricate and require sufficient conditions to operate optimally. Your skin, respiratory tract, and gastrointestinal tract need to be intact and healthy. The immune system needs energy, raw materials, production factories, highways, meeting places, communication systems, and elimination processes. These things come in the form of macro and micronutrients, vascular systems, and organs.[*] Your diet, sleep patterns, hydration status, sun exposure, and stress can all play a role in how effectively your army gets what it needs to fight the enemy effectively.
Just to make sure we are all on the same page here - COVID-19 is the disease caused by the novel coronavirus SARS-CoV-2. “SARS” stands for severe acute respiratory syndrome, and “CoV” stands for coronavirus. The “2” is there because SARS-CoV-2 is 82% genetically identical to another known coronavirus, SARS-CoV[*][*], which I will refer to as SARS-CoV-1. We’ll discuss why this important later.
Supporting the Troops
The Ketogenic Diet
Many of you have come to this blog because you are interested in, or are currently on a low carbohydrate, or Ketogenic Diet. So, let’s start there.
Is the ketogenic Diet good for the immune system?
First, it’s important to note that people will respond a little differently to any given diet based on genetics, age, activity level, environment, stress, sleep habits, state of health, and other factors known and unknown.
Diversity in individual response to diets, including the Keto Diet, can also be caused by food choices, individual food sensitivities and allergies, meal timing, medications, and supplements.
Considering the above statements, one should always carefully consider their state of health, and closely monitor their response to dietary changes. As always, it’s a good idea to consult with a qualified health professional to determine a diet that is right for you, and to monitor your response. Especially if you have any kind of health condition.
The Ketogenic Diet is based on a specific macronutrient ratio, which leaves a lot of room for interpretation when considering individual food choices. You can eat a really healthy Ketogenic Diet, complete with non-starchy vegetables, nuts, fresh meats, fatty fish, high quality and heart healthy oils, or you can eat a junk food Ketogenic Diet chocked full of poor-quality oils, processed meats, and no veggies. Although both versions are within the realm of the Ketogenic Diet, you could have a very different response based on which way you choose to eat.
All of that considered, we’ll explore what we know about the Ketogenic Diet and how it generally affects the immune system.
While conclusive research remains limited, it appears that the Ketogenic Diet can benefit your immune system by:
- Decreasing chronic systemic inflammation
- Decreasing fat mass
- Promoting stabile blood sugar
- Improving immune cell function
As no diet is perfect, the Ketogenic diet may have some downsides for the immune system that will be discussed at the end.
Decreases Systemic Chronic Inflammation (SCI)
The immune system is a very complex and beautiful thing. The inflammation response keeps us safe from invading pathogens and promotes tissue healing. It is invaluable. Without such a dynamic system, we would swiftly perish.
However, the immune system requires balance and sometimes it malfunctions. A normal inflammatory response occurs when a threat is present, and it resolves when the threat is eliminated. Sometimes, however, the inflammatory process occurs when a threat is not present or persists even after the threat is eliminated.[*] When an inflammatory response occurs and does not resolve as it should, it can lead to systemic chronic inflammation (SCI).
SCI is a low grade, persistent type of inflammation, and is thought to contribute to many chronic diseases, such as type 2 diabetes, cardiovascular disease, various types of cancer, and others[*] Additionally, SCI can impair normal immune function and make you more vulnerable to infections.
Stress, excess body fat, exposure to environmental toxins, poor nutrition status, and pro-inflammatory foods- such as isolated sugars and processed carbohydrates–can all result in SCI.[*]
How do you know if you have Systemic Chronic Inflammation (SCI)?
There are a few biomarkers that healthcare professionals can measure to get a picture of your general inflammatory status[*] Some common ones found in research are high sensitivity C-reactive protein (CRP), tumor necrosis factor (TNF), interlukin-1 (IL-1), interlukin-6 (IL-6), white blood cells (WBC), and adiponectin. CRP is considered a particularly reliable measure of SCI, as well as a strong predictor of cardiovascular disease[*] While results are mixed, most research shows that the Ketogenic Diet improves these biomarkers, thus improving inflammatory status. In this respect, a well-formulated Ketogenic Diet may contribute to a well-functioning immune system.
- Research in patients with type II diabetes on a Ketogenic Diet for 2 years showed significant decreases in CRP and WBC values at the 1-year and 2-year marks, whereas patients who were receiving usual care saw no change in these values.[*]
- Perissiou et al studied obese individuals who participated in an exercise program and consumed either their normal diet or the Ketogenic Diet for 8 weeks. While both groups saw decreases in their CRP levels (because exercise alone has been shown to decrease CRP[*]), the individuals on the Ketogenic Diet had greater decreases in CRP than those consuming their typical diet[*] In other words, exercise + Keto improves inflammation better than exercise + standard diet.
- Next, obese individuals participating in a study without an exercise program for 12 weeks saw significant increases in the anti-inflammatory molecule adiponectin by the 8-week mark[*] Interestingly, this group saw an initial increase in CRP during the first 2 weeks of the Ketogenic Diet, which then trended down returning to baseline by the end of the study. The downward trend may have continued if the study continued. The authors concluded that the Ketogenic Diet resulted in improved inflammatory status.
- Lastly, a study of overweight and obese individuals on the Mediterranean Ketogenic Diet, including phytoextracts and a multivitamin for 4 weeks saw a significant decrease in TNF[*] The subjects who were on the Mediterranean Ketogenic phytoextract multivitamin Diet PLUS an omega-3 fatty acid supplement, saw even greater improvements in TNF, as well as additional decreases in IL-1 and IL-6, and a significant increase in anti-inflammatory adiponectin.
While these, and similar studies, have limitations, the general picture developing is that the Ketogenic Diet improves inflammatory status.
How Does the Ketogenic Diet Decrease Inflammation?
The Ketogenic Diet appears to achieve its anti-inflammatory prowess through antioxidant activity, as well as by activating some immune cells and inhibiting others in a way that helps resolve inflammation.[*]
Another important anti-inflammatory component of the Ketogenic Diet is beta-hydroxybutyrate (BHB), the primary ketone used for energy when in ketosis. BHB produces fewer reactive oxygen species (ROS) than glucose does when processed for energy.[*] This puts less oxidative stress on your body, and since oxidative stress activates inflammatory pathways, BHB produces less inflammatory potential.[*]
Aside from providing your cells with energy, BHB also inhibits the pro-inflammatory receptor known as the NLRP3 inflammasome. This receptor initiates an inflammatory cascade and is associated with type 2 diabetes, cardiovascular disease, Alzheimer’s disease, and other chronic diseases when it is overactive.[*]
Back to COVID-19
As it turns out, SARS-CoV-1 (remember SARS-CoV-2’s close relative?) inflicts it’s turmoil on the immune system, in part, by activating the NLRP3 inflammasome.[*] Since these bad boys are 79% genetically similar, it’s quite possible that SARS-CoV-2 (COVID-19) does the same thing.[*] Therefore, consuming the Ketogenic Diet, which produces a high amount of BHB that inhibits the NLRP3 inflammasome may decrease the severity COVID-19 if you are infected.
To be clear, I’m not suggesting that you should start a Ketogenic Diet if you find out you have the coronavirus. That probably isn’t a good time to make such a drastic dietary change. On the other hand, if you are already on the Ketogenic Diet, this is a possible and theoretical mechanism that might decrease the severity of COVID-19 symptoms. If you do find yourself sick, it may be very helpful to start avoiding pro-inflammatory foods such as ultra-processed carbohydrates and isolated sugars, especially if you are at high risk of severe infection!
- The Ketogenic Diet appears to decrease inflammation as evidenced by improving inflammatory markers
- This anti-inflammatory effect may boost the immune system by removing the burden of systemic chronic inflammation
- The anti-inflammatory effects appear to be enhanced by choosing foods consistent with both Keto and the Mediterranean Diet
- Regular exercise also appears to improve the anti-inflammatory effects of the Ketogenic Diet
- Symptoms of COVID-19 may be caused in-part by activation of the NLRP3 inflammasome
- BHB from the Ketogenic Diet inhibits activation of the NLRP3 inflammasome, potentially decreasing COVID-19 severity
Decreases Fat Mass
Obesity has been identified as a risk factor for COVID-19 hospitalization in patients under 60.[*] This means that the COVID-19 infection tends to be more severe in obese individuals.
The human body is built to conserve energy. When you consume more calories than you burn, your body stores those calories for a rainy day. This is a vital adaptive ability that has allowed the survival of humanity during times when food was scarce. However, eating a diet high in processed carbohydrates and isolated sugars set this adaptive ability on overdrive by triggering a hormonal cascade involving weight-promoting peptides like ghrelin and insulin.
Our bodies are excellent energy conservers – use only what you need and store the rest… indefinitely. That’s right, humans have an incredible capacity for energy storage. According to the Guinness Book of World Records, the heaviest man alive weighed a WHOPPING 1,105 lbs. at his peak![*] That is literally half a ton of energy storage!
These days, in industrialized countries, not only is food overly abundant, but we don’t have to work very hard (or at all) to get it. Therefore, it’s very easy to overconsume. Processed foods are designed to be highly palatable and tend to be energy dense (high calories), yet devastatingly low in immune-supporting vitamins, minerals, and phytonutrients. These foods also tend to be high in refined carbohydrates, which stimulate obesity-promoting hormonal pathways. Consuming highly palatable, energy dense, nutrient deficient, refined carbohydrate food is a recipe for obesity.
What is Obesity?
Obesity is the clinical term for excess fat mass that results in a BMI of 30 or above.
I have to pause here because I know some of you are getting disgruntled at the mention of BMI. The BMI metric is not perfect since it only considers height and weight and does not take into account what your weight is composed of, otherwise known as body composition. Therefore, some individuals, such as body builders, can be miscategorized. Bodybuilders may be categorized as overweight or obese based on BMI alone, even though their weight is clearly made up of muscle mass rather than fat mass. For this reason, on an individual level, BMI should not be the only factor that determines an individual’s weight status.
On the other hand, BMI provides an accurate weight status for most people. In individuals that are legitimately obese, reaching this level of fat mass leads to adipocytes (cells that store fat) that grow too large and begin to produce pro-inflammatory molecules. This causes systemic chronic inflammation (SCI), which is thought to be the connection between obesity and chronic diseases like type 2 diabetes and cancer.[*]
As discussed in the previous section, SCI impairs the immune system and increases the risk of infection[*] It should not be surprising, then, that obesity also increases the risk of infection,[*] and that obese individuals are at greater risk for hospitalization related to COVID-19.
The Ketogenic Diet is an effective method of decreasing body fat, [*] especially visceral fat,[*] which tends to be more inflammatory than other fat.[*] This could be another way the Ketogenic Diet decreases inflammation, and potentially decreases the risk of infection or severity of infection. Remember, by decreasing the burden of systemic chronic inflammation, the immune system can more effectively combat infections.
- Obesity causes systemic chronic inflammation
- Obesity is associated with increased risk and severity of infections, including COVID-19
- The Ketogenic Diet is effective at reducing obesity
- Reducing obesity decreases inflammation
- Reducing obesity decreases risk and severity of infection
Helps Stabilize Blood Sugar
Glucose (sugar) is a vital nutrient for human life. HOWEVER, if there is too much sugar in the blood, it can wreak havoc on every bodily system, including the immune system. People with diabetes have chronically high blood sugar. This is either because they do not produce enough insulin, their cells are not sensitive to insulin, or a combination of the two. Insulin acts as the key to allow sugar to enter cells. When sugar enters cells, the sugar is removed from the blood. When sugar cannot effectively enter cells, then it has no choice but to stay in the blood, causing high blood sugar, otherwise known as hyperglycemia. People with diabetes have chronically high blood sugar, which puts them at significantly higher risk of infections compared to the general population.[*]
Additionally, surgical patients and critically ill patients who develop hyperglycemia are prone to infections and are at greater risk for poor medical outcomes (*). This demonstrates that even short-term hyperglycemia can have a negative impact on the immune system. Therefore, drinking sugary drinks or eating cakes, candy, bread, rice, cereal, potatoes, and other foods that cause blood sugar spikes may have negative consequences for your immune health. Occasional blood sugar spikes are unlikely to have a meaningful impact, but daily spikes certainly could.
When too much sugar is in the blood, it starts to bind with other things in the blood, like proteins. When this happens, the result is called an advanced glycation end product (AGEs). AGEs can trigger inflammatory pathways.[*] Whatever glucose binds to no longer works the way it’s supposed to. So, whatever that thing was supposed to do, it can no longer do. For example, hemoglobin is a protein in red blood cells that carries oxygen throughout the body. When blood sugar is high, glucose binds to hemoglobin and it can no longer carry oxygen effectively.[*] Doctors measure the amount of oxygen-bound hemoglobin in a person’s blood and use this measure to diagnose diabetes. This measurement is called HbA1c, and it approximates blood sugar levels over the previous 3 months.
Sugar does the same thing to components of the immune system. One example is the compliment system, which is a group of proteins that play a number of important roles in fighting infections. When glucose is elevated, it can bind to these proteins and impair their ability to kill invaders.[*]
Elevated blood sugar has been documented to impair communication between immune cells, decrease recruitment of white blood cells, impair the immune system’s ability to recognize an invader, and impair the activity of cells that kill invaders.[*]
Additionally, glucose metabolism creates reactive oxygen species (ROS). The more glucose being metabolized, the greater the oxidative burden and inflammation.[*]
Therefore, to maintain the highest quality immune system and the strongest and most well-coordinated military, you should make sure you have stabilized blood sugar in the healthy range.
You can achieve stable blood sugar by following a healthy diet and exercising regularly. Consuming a generally healthy diet limited in refined carbohydrates and soft drinks is a major key. A nutrient-dense low carbohydrate diet and the Mediterranean Diet are two good examples of healthy eating patterns that will improve your blood sugar. TheAmerican Diabetes Association (ADA) is a good resource for people with diabetes, or anyone interested in controlling their blood sugar. The ADA recently endorsed a low carbohydrate diet as an effective treatment intervention for individuals with type II diabetes.[*][*]
Additionally, the Ketogenic Diet has shown great promise in this realm. People on Keto tend to maintain blood sugar in the healthy range and often report no longer suffering the mid-day fatigue that accompanies a sugar crash.[*][*][*] This is mainly because Keto Dieters are not consuming large amounts of sugar at one time and they are avoiding sugary foods. Instead, they are consuming relatively small amounts of sugar over the course of the entire day. In this situation, the main energy source for your body switches from sugar (glucose) to fat. Using fat as energy preserves sugar levels in the blood for the few cells that really need it.
Keto appears to work well for patients with diabetes. It helps them lose weight, decrease blood sugar, decrease HbA1c, and decrease systemic chronic inflammation,[*] all of which is expected to improve their immune system.[*]
- Elevated blood sugar interferes with several aspects of the immune system
- Patients with diabetes and uncontrolled blood sugar are at significantly greater risk for infections
- Surgical patients and critically ill patients who develop hyperglycemia have worse medical outcomes
- Diet and exercise can play a critical role in regulating blood sugar
- The Ketogenic diet is effective at reducing blood sugar in those with hyperglycemia
- The Ketogenic diet is effective at maintaining steady blood sugar, thus reducing the sugar burden on the immune system
May Improve Immune Cell Function
The metabolic adaptations that occur while on the Ketogenic Diet may enhance the activity of certain immune cells. A study from researchers at Yale University found that mice fed a Ketogenic Diet had special immune activation that protected them from influenza infection.[*][*] Mice on the standard, high carbohydrate diet did not have this protection.
We should always be cautious drawing conclusions from animal studies, as they do not always directly represent what happens in humans. Nevertheless, this study is exciting and demonstrates that the Ketogenic Diet might enhance immune function by directly activating immune cells.
- Mice on Ketogenic Diet were more resistant to influenza virus than mice on a standard diet
- May be evidence that the Ketogenic Diet directly enhances the immune system
- More research is needed to verify this effect is similar in humans
The Potential Downside
What you eat is ABSOLUTELY an important factor determining the strength of your immune system. There is even a whole scientific discipline devoted to understanding the complicated influence that nutrition has over the immune system called nutritional immunology.[*] While some foods support and optimize immune regulation, others impair the immune system. Additionally, your immune system requires many tools that come from the food you eat, and some dietary patterns simply lack some of the tools the immune system requires to function optimally.
This leads us to the potential downside of the Ketogenic Diet. A criticism of the Ketogenic Diet is that it is quite restrictive. On one hand, its restrictive nature is great, because it severely limits the amount of junk food you can eat. On the other hand, it limits food choices in a way that might make it difficult for some Keto Dieters to get sufficient amounts of nutrients to optimize immune function.
The next installment of the immune boosting series will discuss what you need in your diet to ensure optimal immune function no matter what diet you are on.