Recommendation: First, learn the basics of health; figure out how to get adequate sleep, balanced nutrition, healthy relationships, and effective exercise. Get to where you’re performing well most days, and when you don’t feel great, you have a good idea why (you stayed up too late/didn’t eat well/skipped the gym). Until then, the detail-heavy bottom half of this article won’t likely be helpful unless you simply like to read boring research! If you’re not trying to fall asleep, I recommend to only read the first couple of paragraphs so that when you hear about it on TV or your favorite podcast you can follow along, as those discussions get technical. The purpose of this article is to provide information surrounding the research of ketosis for those who do have a grasp on health–specifically nutrition–and who want to learn about this relatively new and popular topic of research.
In short, clinically conclusive benefits of being in long-term ketosis are only shown in children suffering from seizures who don’t respond to drugs. That’s the main population which is clinically treated with this diet, and thus is the target of the vast majority of research. Conversely, long-term ketosis in healthy adults is not greatly understood, though it has grown in popularity recently with the rediscovery of low-carb dieting (paleo, primal, Atkins, and even caloric restriction). I have limited formal education on nutrition, but it seems to me that research around nutritional ketosis–in healthy adults–is similar to research around eating fermented foods in a few ways. Both are almost century-old topics of research, even though both are relatively new in the spotlight. Since emerging, both have research suggesting there may be great health benefits for normally healthy individuals. Both are also shown to be effective treatments for specific diseases, and are easily incorporated in the short-term. However, two shortcomings should prevent overexcitement about ketosis and probiotic foods–we don’t know enough about either in respect to how it affects individuals differently, and also–as with most diet-related research–both of these topics don’t inherently at this time target nor necessitate “healthy” foods. In other words, you can get into ketosis eating processed fats, but is that the same as a diet of unprocessed whole-foods which happen to be high in natural fats? Likewise, we’re far away from being able to give sound advice to healthy people in regards to which fermented foods to eat, how to prepare them, how much will provide which probiotic benefits, etc. Does sleep quality affect the benefits of these diets? How about exercise? This is where balance, variety, and moderation come into play and a basic knowledge of health is key. We know some people seem to benefit from these dietary choices (ketosis, probiotic, or otherwise), but we’re not yet able to give specific, actionable advice on a large scale because there are very unhealthy ways to do it. At least, the advice we can be certain is sound advice for those trying ketosis/probiotic food is simply the same dietary advice we see across all diets, generally (eat veggies, limit added sugar, whole foods, moderation, etc.). Therefore, I don’t consider ketosis to be among the first places one should look to improve their health. Rather, I think it is something for people who already have an idea of healthy eating, sleeping, and exercising habits and may want to learn new ways to cook with healthy fats, maintain low blood glucose, or control weight using a method which doesn’t just limit calories. For myself, I just enjoy learning how the body uses food and how to cook with different ingredients to put that learning into practice.
What is ketosis?
It’s a state measured by presence of ketone bodies in the blood, urine, or breath. It happens quickly as a result of fastling, but more slowly when induced by a diet low in carbs (or high in certain fats, as mentioned later on). This latter scenario (called dietary or “nutritional” ketosis) is an effective common treatment for epileptic children when drugs are ineffective. Ketone bodies created by the body in this state are acetone, beta-hydroxybutyrate, and acetoacetic acid (acetoacetate), and levels of each can be measured in a different way. Acetone can be tested (and smelled) in breath when we are “in ketosis”, at least for a short period at first.1 Blood level of beta-hydroxybutyrate is the preferred measurement, which remains accurate even at low levels as long as a person remains in ketosis.2 One study mentions: “All subjects following the ketogenic diet had β-hydroxybutyrate concentrations > 0.20 mmol/L, indicating compliance with the ketogenic diet.”3 That study also measured presence of acetoacetate in the urine. However, acetoacetate is a byproduct of the body’s adaptation to ketosis. Therefore, this metric seems only valid for a few days or weeks as the body gets more efficient at creating/reabsorbing ketones. As that happens, less is excreted in the urine.4 Ketosis can be achieved pretty quickly, especially if a ketogenic diet follows a brief fast (12 hours/overnight).5
One study explains:
After about 12-24 hrs of fasting, liver glycogen depletes… A supply of glucose is necessary, especially for the nervous system and erythrocytes. Death usually results if gluconeogenesis fails [cited]. At the same time, concentrations of insulin and glucose decrease (glucose decreases toward ≈3 mmol/L) while glucagon increases. These changes initiate a strong increase in the concentration of free fatty acids as the body switches from the fed state to the starved state. Although slightly delayed, the concentration of blood ketone bodies increases from a negligible value to ≈2 mmol/L [cited]. As noted decades ago, after ≈3 days, hunger decreases considerably as the concentration of these ketone bodies continues to increase to >4 mmol/L [cited]. Ketosis arises because the major fuel being burned is fat from body stores. The brain spares some glucose by using these ketone bodies. This mild ketosis is the body’s natural adaptation to starvation and is not to be confused with the dangerous ketoacidosis associated with untreated type 1 diabetes.6
How do I get “into ketosis”
Pretty easily, it seems. Research has shown that it takes about 24-48 hrs of fasting for children up to 18 yrs to prominently show ketones in urine.7-8 That resulted in a rating of 80 mg/dL (8 mmol/L) or higher on ketone-testing sticks, which is “deep ketosis”. To maintain that, these 4-6 month studies also use either a “traditional” 3 or 4:1 ratio (by food-weight) ketogenic diet (about 90% calories from fats) or an MCT-supplemented ketogenic diet (40, 50, or 60% calories from MCT oil, and 31, 21, or 11% from non-MCT fats). Either way, it seems to be achievable within days for everyone, assuming the right amount/type of fats are consumed.
Why Does This Happen?
If we don’t eat, our body turns to this ketosis process for energy. We could also induce ketosis eating a nutritionally-balanced diet, if our diet is high enough in certain fats and low enough in carbs. It’s not exactly that simple; certain fats accelerate this process, and the ‘limit’ of carbs is different for each person, but that’s the general rule. Still, in nutritional ketosis some glucose is made and used for the types of cells which can’t use fat or ketones for energy, and thus depend on glucose (e.g. eyes, kidneys, testis, and red blood cells). Other cells which can use anything (glucose, ketones, or fatty acids) shift to use more ketones/fatty acids to spare glucose. Another group of cells (e.g. nervous system) can use either glucose or ketones and will shift to use more ketones to spare even more glucose.9
Specific, yet inconclusive, benefits of nutritional ketosis
Other than weight management, cardiovascular health has been seen to improve in some subjects in short to medium-term studies. For example, 87 subjects who previously got >50% of their calories from carbs maintained a Mediterranean-style ketogenic diet for 6 weeks. At the beginning of the study they exhibited certain risk factors (e.g. BMI>25, total cholesterol>3.5:1). By the end, they saw significant improvement in several measures including lowered triglycerides, LDL and total cholesterol, and increased HDL (thus, improved cholesterol ratio).10 Annoyingly, this study didn’t mention the level of ketosis subjects were in. Without knowing blood/urine/breath measurements, we don’t know if results could come easily or from only strict adherence to the diet. Also, the diet provided below 1200 calories/day on average, which isn’t practical for most. Still, the study cites several others which display similar results among different populations. This body of research causes some–especially within the fields of medicine and nutrition–to question if the fear of fat is warranted among USDA dietary guidance. Research has also shown an improved lipid profile when subjects achieve ketosis after 4 months supplementing their diet with “medium chain triglycerides” (MCT oil).11 This study did make sure subjects were in “deep ketosis”, with urine ketones reaching at least 8 mmol/L, but they didn’t report how deep they stayed in ketosis throughout the 4 month study. We’re left to assume they did, which is likely, considering the diet. However, it’s not helpful for those of us who want to know if we must reach that deep level of ketosis to make a difference. Also, I have two mild concerns: they witnessed a non-significant opposite effect from a classic ketogenic diet and they didn’t explain what specific foods were being eaten.
Nutritional ketosis has also been shown to favorably change LDL particle size (LDL-p) among young, healthy men; that is, it increased the mean and peak LDL particle size, especially among subjects exhibiting “pattern B” distribution (predominantly small, dense lipoproteins which increase cardiovascular disease risk).12-13-14-15 This study was too short and had too small a sample to conclude its validity, but it was repeated in a small group of healthy women with slightly different, but similarly promising results. The women didn’t experience the same favorable change in LDL-p, but HDL increased 33% on average. This sent 6/10 women from HDL <60 mg/dL to >60 mg/dL (the point at which it’s shown to reduce CVD risk). For what it’s worth, both studies were supported by grants from the Atkins foundation.
What are the risks?
Same as the benefits, we aren’t certain about the significant risks of nutritional ketosis in healthy adults. Many studies show growth retardation in children on the diet long-term, supposedly due to lower activity of IGF-1.16 However, I’m concerned with risks to healthy adults. Possible risks include lean mass loss, since at least 1.2g-1.7g of protein per kg body weight (about 15% of calories) are required to maintain nitrogen balance and lean mass while on the diet.17 For me, that’s 80-110g of protein per day. That’s 5 eggs and an 8-ounce steak (most cuts); or 6oz salmon/tuna/halibut, 4oz greek yogurt, and 6oz tofu. All that would be in addition to other sources, like dairy, nuts, and beans.
Another, somewhat related risk is loss of electrolytes. Supplementing a ketogenic diet with 3g sodium and 1g potassium daily is recommended by one study, as it explains, “With these supplements maintaining daily intakes for sodium at 3–5 g/d and total potassium at 2–3 g/d, our adult subjects were able to effectively maintain their circulatory reserve (ie, allowing vasodilatation during submaximal exercise) and effective nitrogen balance with functional tissue preservation.”18
The relative lack of clinically-proven benefits and presence of reason-based and clinically-suggested risks makes nutritional ketosis too young an idea to be commonly recommended for healthy adults. Still, it’s gaining popularity in research and should be familiar to those interested in all things related to optimizing health. It’s not about preventing disease–that’s in the realm of balance, variety, and moderation. It’s more about performing at the highest level possible, which many people are interested in. For that reason, if it’s soon shown to be harmless, and has potential benefits to those willing to make the effort, it’s a concept worth following.