One of the things that really struck me as I started delving into the research behind the paleo diet was how little actual, good, peer-reviewed research has ever been done that supports the conventional wisom of fats make you fat, high-carbs are good for your metabolism, cholesterol will give you heart disease, and so forth. But despite all this, people still insist on repeating the party line. Being a scientist, I’ve often gone to lengths to track down the “good” research that proved these ideas faulty. Unfortunately, sending these papers and sources to people has had mixed results.

So imagine my surprise when one of my good friends who has been really skeptical of all the paleo research I’ve told him about sent me a link to this article the other day. It discusses the use of very-low-carb (VLC), or ketogenic, diets as therapy for a range of diseases and conditions, and cites many research studies as support for each of its conclusions. My friend was impressed with the article, and–once I read through it–I was pleasantly surprised as well. The article takes a large stack of supporting research and boils it down to concise points, in a way that many other writers and researchers in this field that I have read have struggled with.

The jargon can be a little dense, though, especially if you’re not used to reading professional science papers. Since technically I am a professional science writer, I decided to break down some of the key points of this article in the hopes that you can send it to some of your skeptic friends and have a smack down an informed debate with them.

First off, understand that this isn’t the same as a research paper. It is a review article, which is an article that takes a lot of different research articles and uses them to paint a larger picture and argue an underlying point. Kind of like a chapter in a textbook, or even a research essay. Review articles are great, though, because they point you to where all the good research papers are without having to go dig around for them.

The article opens by describing what VLC/Ketogenic diets are, shortening the term to “VLCKD.” Nowhere in the article do they use the word “paleo,” but that was probably to avoid the knee-jerk reaction a lot of people have against the paleo diet these days. They discuss the fact that ketogenic diets have been widely accepted as a successful treatment for epilepsy since the 1920s, and only fell out of fashion for awhile once anticonvulsant drugs were invented (one of the early warning signs of our society’s pill addiction, IMO). They even bring up the interesting point that there seems to be a reference to ketosis as a treatment for epilepsy in the Bible, citing Matthew 17:14-21. I looked it up, and in the New King James version that passage reads:

14 And when they had come to the multitude, a man came to Him, kneeling down to Him and saying, 15 “Lord, have mercy on my son, for he is an epileptic and suffers severely; for he often falls into the fire and often into the water.16 So I brought him to Your disciples, but they could not cure him.” 17 Then Jesus answered and said, “O faithless and perverse generation, how long shall I be with you? How long shall I bear with you? Bring him here to Me.” 18 And Jesus rebuked the demon, and it came out of him; and the child was cured from that very hour. 19 Then the disciples came to Jesus privately and said, “Why could we not cast it out?” 20 So Jesus said to them, “Because of your unbelief; for assuredly, I say to you, if you have faith as a mustard seed, you will say to this mountain, ‘Move from here to there,’ and it will move; and nothing will be impossible for you.21 However, this kind does not go out except by prayer and fasting.”

Depending on the time frame or how it was structured, fasting would be one way to trigger ketosis, which might have worked as an ancient treatment for epilepsy, aka “demon possession.” Who knows when all the candles and crap got added.

Anyway, the article of course then goes on to describe what ketosis is:

“After 3–4 days without carbohydrate consumption the [central nervous system] is ‘forced’ to find alternative energy sources….This condition seen in prolonged fasting, type 1 diabetes and high-fat/low-carbohydrate diets leads to the production of higher-than-normal levels of so-called ketone bodies (KBs)…a process called ketogenesis….KBs are then used by tissues as a source of energy.”

In other words: when you avoid eating carbohydrates, most of the cells of your body can run on fats, but the central nervous system (brain and spinal nerves) cannot, so your body produces molecules called ketone bodies, or ketones. These are used by your central nervous system and other tissues as a replacement energy source via different metabolic pathways than your body’s cells would normally use for carbohydrates. Something about using these alternate metabolic pathways gives ketogenesis a therapeutic effect for many diseases and conditions, for reasons that aren’t yet entirely understood in all cases. This article discusses what therapeutic effects have been seen so far by using ketogenic diets and proposes many explanations and hypotheses about why they work.

What I really like about this paper is that they take explicit effort to distinguish between ketogenesis and ketoacidosis, the latter of which is a dangerous condition and often a sign of late-stage diabetes or kidney failure. Although both of these conditions have “keto” in the name and involve ketones in some way, they are not the same. Large-scale misunderstanding of this difference–including within the medical community–has been a lot of the reason behind the backlash against ketogenic diets in the first place. This article very neatly summarizes the differences between these two conditions in the following table:

As you can see, ketoacidosis is characterized by extremely high levels of glucose and ketone body (KB) concentration and a low blood pH, while ketogenesis has numbers barely different from a “normal” diet.

The article then goes on to discuss the specific evidence for using ketogeneic diets as therapy for a range of conditions. They start by going over the conditions wherein there is already a strong collection of evidence: weight-loss, cardiovascular disease, type-2 diabetes, and of course epilepsy. For each condition, they cite and discuss multiple published research studies. I won’t go over each of them here, but the discussion on each condition is clearly labelled so you can jump right to the one you are interested in.

The next section, though, talks about new areas of research that show the effectiveness of ketogenic diets. The other conditions with such emerging evidence include acne, cancer, polycystic ovary syndrome (PCOS), and neurological diseases like Parkinson’s, Alzheimer’s, multiple sclerosis (MS), and even autism. Their summary of the conditions that might be treatable through ketogenic diets and the possible mechanisms explaining why they work is outlined in this handy little concept map:

They do point out, though, that much of the evidence in these new areas of research have only been done in animal trials so far and so one needs to be careful to extrapolate this data to humans. I’m willing to take the risk, though, considering how many stories I have heard of women sucessfully treating their PCOS with paleo (or even just gluten-free) diets, and no one can ignore the amazing story of Dr. Terry Wahls successfully treating her advanced case of MS by filling her diet with fresh, colorful vegetables and other real foods.

The last section of the paper discusses the possible risks of a ketogenic diet, basically addressing the unspoken question of, “Ok, well even if ketosis isn’t the same as ketoacidosis, it still puts a lot of proteins in the blood so it’s bad for the kidneys, right?” The answer to that question is, “Not necessarily.” As they point out:

“If we equate [the average] ketogenic diets with high-protein diets (which is not always correct) then the risks proposed by critics of this type of dietary approach are essentially those of possible kidney damage due to high levels of nitrogen excretion during protein metabolism….There is not wide agreement between studies; however, some infer the possibility of renal damage from animal studies, whereas others, looking at both animal models…and human studies, propose that even high levels of protein in the diet do not damage renal function. In subjects with intact renal function, higher dietary protein levels caused some functional and morphological adaptations without negative effects.”

So putting a lot of proteins in your blood is dangerous for your kidneys, except that it might not actually be dangerous for your kidneys. In addition:

“Moreover, it should be noted that ketogenic diets are only relatively high in protein.”

Which is certainly true in the paleo sense of the diet. Ideally, we are getting most of our calories from fats. If someone is trying to do the old school “low-carb-low-fat” modalities of paleo (the ones that advised people to only eat lean muscle meat (blech) instead of good quality fats and organ meats, an approach that I call “Fail-eo”) then proteins are literally the only major macronutrient your body has to derive energy from. Breaking down only proteins, and lots of them, might in fact put a dangerous amount of amino acids into your bloodstream. But if you’re reading this, hopefully you’re on the side of low-carb-high-fat, so this issue might be a moot point.

So that concludes my discussion of this article. (Look at me, reading and critiquing scientific papers, in my spare time, for fun. My graduate school advisor would be so proud.) I hope you check it out and share it as you see fit. If you have any questions, either about things in the article or my own ramblings, please do not hesitate to ask me in the comments!