Mass Action

I've started reading Dr. Richard D. Feinman's book, The World Turned Upside Down: The Second Low-Carbohydrate Revolution. It may be the best book on the topic of low carb diets to date, because of its broad perspective, and its readability. It appears to have at its core the same thesis Zooko and I have been trying to promote on our website, that low carbohydrate diets are good for health in many ways, particularly in ways connected to metabolic syndrome. In the book, Dr. Feinman expresses a problem that comes with that discovery, a problem which has caused us much personal frustration:

"[T]he problem with convincing people of the benefits of a reduced carbohydrate strategy is that it appears to be good for everything, good for what ails you. You can sound like a hard-sell pitchman." (p 204)

Another passage that particularly struck me was in the introduction. It has given me vocabulary for a concept we've tried to express several times.

"[B]iology tends to run on hormones and enzymes, that is, control mechanisms, not on mass action (the principle that chemical processes are determined by how much reactants are put into them). The grand principle in biochemistry is that there is hardly anything that is not connected with feedback." (p 7, Emphasis ours)

This point was made in the context of the diet-heart hypothesis, which has as a premise that you can control the amount of cholesterol in your blood by how much of it you eat (which is untrue). It is an equally appropriate concept when talking about the calorie control method for weight loss. That method is generally a lost cause, because the important mechanisms in weight control are hormonal. How much you eat is a downstream effect of your hormonal state.

Protein does not affect ketosis via mass action

It also explains well the idea Zooko and I have tried to put forth about protein and gluconeogenesis (GNG, the process of making sugar out of protein). We showed in this post that the amount of material available for GNG doesn't appear to have any effect on how much GNG actually occurs. Insofar as eating a high amount of protein can lead to reduced ketosis, which would then require your body to get more energy from glucose, which could increase demand for GNG, this must occur through a hormonal/enzymatic cascade.

That would mean that managing ketosis is not a simple matter of calculating some threshold of protein, after which the rest "turns into sugar", any more than managing weight is a simple matter of calculating some threshold of calories, after which the rest "turns into fat".

Most people find that if they restrict carbohydrate intake, excess fat is lost. The loss of fat entails a caloric deficit, but that is an effect of the fat loss, not a cause. One could argue about what would happen if people on low carb diets consumed excess calories, but it's largely irrelevant, because people on low carb diets following their hunger rarely do that.

The same may be true of protein. As far as I can tell, most people on a very low carb diet are in ketosis without consciously constraining their protein consumption. It happens naturally.

While I have heard from some people who need to manually manage calories or protein to stay in their therapeutic zone, even while on a very low carb diet, it doesn't seem to be the common case. Even in those cases, I have often seen the problem resolve when a high-fat, plant-free, sweetener-free approach is taken. This suggests that there are further (hormonal/enzymatic) mechanisms that can interfere with the hunger feedback loop.

The mystery of hippopotamus fat

A friend recently drew my attention to an historical essay about a plan to bring hippos to the U.S. primarily for eating. Unfortunately, that plan never came to fruition. Hippos are one of the fatter animals left, endangered because their meat is so prized, and I wonder why we don't just farm them.

In any case, I was curious about eating hippopotamus, and found an interesting section on hippopotamus fat in The Paleoanthropology and Archaeology of Big-Game Hunting: Protein, Fat, or Politics?.

As is evident from some of the previous quotes, the hippo, like the eland, was clearly highly prized for its fat (e.g. Andersson 1857:414; St. Gibbons 1898:9). While hippos may have been too difficult and too dangerous for Paleolithic hunters to kill, it is perhaps not surprising that (presumably) scavenged hippo remains, with clearly cutmarked bones, often show up in some of our earliest archeological sites in East Africa, such as the famous HAS ("Hippo and Artefact") Site immortalised in a stamp issued jointly in 1975 by Kenya, Tanzania, and Uganda (see Fug. 4.4; Isaac and Harris 1997; for additional early cases, see also Bunn 1994; Clark 1987; Fiore et al. 2004; Harmand et al. 2009; Johanson and Wong 2009:255; Leakey 1996:70-71; Plummer et al. 1999;Pobiner et al. 2008).

William Burchell in 1822 provides a concise but useful description of hippo fat, noting its quantity and its somewhat unusually low melting point:

The ribs [of the hippo] are covered with a thick layer of fat, celebrated as the greatest delicacy; and known to the colonists as a rarity by the name of `Zeekoe-spek' (Seacow-pork). This can only be preserved by salting; as, on attempting to dry it in the sun in the same manner as other parts of the animal, it melts away. The rest of the flesh consists entirely of lean; and was, as usual with all other game, cut into large slices, and dried on the bushes; reserving only enough for present use.

Burchell(1822:411)

Schweinfurth's (1978) interesting narrative provides additional insights into the amount of fat that one can obtain from a single hippo carcass; he also comments on the low melting point of the fat, noting additionally that the fat does not go rancid easily:

We were hard at work on the following day in turning the huge carcass of the hippopotamus to account for our domestic use. My people boiled down great flasks of the fat which they took from the layers between the ribs, but what the entire produce of grease would have been I was unable to determine, as hundreds of natives had already cut off and appropriated pieces of the flesh. When it is boiled, hippopotamus fat is very similar to pork-lard, though in the warm climate of Central Africa it never attains a consistency firmer than that of oil. Of all animal fats it appears to be the purest, and at any rate never becomes rancid, and will keep for many years without requiring any special process of clarifying....

Schweinfurth (1878:192)

I then became curious about the composition of hippopotamus fat. What could make it both have a low melting point and be resistant to rancidity? Generally, the more saturated a fat is, the more solid it is (that is, the higher a melting point), but at the same time, the more stable it is — the less it is susceptible to rancidity, because it can't be easily oxidised. So how could hippopotamus fat be both very liquid, and very stable?

I eventually found a paper which gives the composition of the fat of a variety of even-toed (cloven-hoofed) animals. I was perplexed, because hippo fat appears to be almost the same as beef, and although it has a little more oleic acid and a little less stearic [*], which should make it slightly less solid than beef tallow, it should still be firmer than lard, which has even more oleic and less stearic.

Hope temporarily returned when I realised what the point of the paper was, and I learned something new to me. Fat is usually in the form of a triglyceride. It's called that because it consists of three fatty acids held together by a glycerol "backbone". The thing I hadn't read about or thought about before, is that the properties of triglycerides depend not just on which fatty acids are in them, but what position they are in the triglyceride. There appears to be a whole industry built around that. For example, now that consumers avoid hydrogenated oils, but still think they should avoid saturated fat, and still want something spreadable, engineers have discovered they can make vegetable oils more solid by manipulating the position of fatty acids within triglycerides [†].

Nonetheless, looking at the table in the paper [‡], not only is the proportion fatty acids in hippo fat similar to beef, so is the distribution of those fats into the middle position of the triglyceride. So, the mystery isn't solved that way. I don't know what to think.

Another friend pointed out that there are feral hippos in Columbia that no one knows what to do with. I have an idea...

---

[*]	'Stearic' comes from one of the many different Greek words for fat (as important as snow to the Inuit): στεαρ (stear): 'hard fat', whereas 'oleic' probably comes from ελαιον (elaion): 'oil'. See The lore of lipids, by Lewis Gidez, in the Journal of Lipid Research 1984 Dec 15;25(13):1430-6

[†]

Here is a fascinating review of the effects of these 'interesterification' manipulations: Effects of stereospecific positioning of fatty acids in triacylglycerol structures in native and randomized fats: a review of their nutritional implications Tilakavati Karupaiah1 and Kalyana Sundramcorresponding author Nutr Metab (Lond). 2007; 4: 16.

[‡]

The fatty acid numbers represent chain length and number of double bonds (places where hydrogen could attach), i.e. 0 means saturated, 1 means monounsaturated, and >1 means polyunsaturated. The corresponding names are fatty acid names are: 14:0 16:0 18:0 16:1 18:1 18:2 18:3 mystiric palmitic stearic palmitoleic oleic linoleic α-linolenic "The fatty acid distribution in the triglycerides of these various fats is shown in Table 1. For each fat, the first line gives the composition of the whole triglyceride, the second line gives the composition of the fatty acids in the 2-position of the triglyceride, and the third line (Proportion) reports the percentage of each fatty acid that is in the 2-position. If a fatty acid is randomly distributed among all three positions in the triglyceride molecule, the proportion value will be 33%. The occasional proportion value that is in excess of 100% is attributable to the large relative error where a fatty acid is present in very small amounts." For more tables of the composition of fats and their second-position fatty acids in a variety plants and animals, see: TRIACYLGLYCEROLS PART 1. STRUCTURE AND COMPOSITION

Dear Lyle McDonald,

I read your Open Apology to the Internet yesterday. You are courageous to talk about it, and my heart goes out to you. Although I don't know exactly what trouble you've gotten yourself into, I know the pain of Bipolar II, because I have it. Or I had it. Words get a bit tricky, and I have written an entire essay on whether someone has a disease or not when they show no symptoms .

I have no symptoms of bipolar and have been completely off of medication since I started my current diet. How I stumbled upon what has been my cure was sort of an accident, but having a strong background in ketogenic diets played a role, and much of my expertise, at least in the beginning, was given to me by you, Lyle.

You probably don't know of me, but of course I know of you. I read your work in the late 90's while playing around with the CKD. Later, in 2002, The Ketogenic Diet was out of print and very hard to get, but Zooko somehow procured me a copy, presenting it to me on the occasion of our second wedding anniversary. I studied it carefully.

Lowering carbs always helped my mood, and there are many plausible reasons to believe that a ketogenic diet might treat bipolar (see below), but a ketogenic diet by itself didn't cure my disease, and didn't prevent it from progressing.

Progressing

As you say, bipolar progresses. And one thing that may catalyse the progression is antidepressants. From PsychEducation.org, an excellent resource on Bipolar II:

That antidepressants can cause "switching", bringing on a manic or hypomanic phase, is generally accepted, although how often this occurs is still hotly debated (somewhere between 4% and 40% of the time?).

However, antidepressants may pose bigger risks in the long term. Substantial evidence suggests that antidepressants can induce "rapid cycling". Indeed, it is a standard recommendation for the treatment of rapid cycling to gradually withdraw any antidepressant. In addition, more subtle "destabilizing" effects are possible. Antidepressants may make it more difficult to get a good outcome from an otherwise effective mood stabilizer treatment. There is even a concern that antidepressants may permanently alter the course of a person's bipolar illness, through a phenomenon called "kindling".

I feel strongly that my hypomanias were related to my extensive use of antidepressants.

A hijacked brain

You described bipolar as having a hijacked brain. This is exactly my experience.

Last summer I gave a lightning talk at HOPE X on exactly this. (Unfortunately, it was not recorded.) I compared bipolar disorder to having your brain hacked.

I argued that mood states in bipolar act like drugs in state dependent learning. For example, when I had periodic bouts of anger (which increased in frequency as time went on), it was very easy to remember all the things I had been thinking about last time I was angry. It gave the illusion of continuity; that my entire life was one constant stream of things making me angry.

But I had multiple moods, and my beliefs about life in different states were beginning to diverge from each other, based on this contrast in the strength of memory of evidence. I knew this was happening, but it created a dilemma: Do I act on what I think I might believe later, or what I believe now? To whom am I loyal — myself now, or the self I know I will be later?

Specifically, what should I do when in that state in which I know that life is not worth living, because my whole life, it seems then, has been one long stream of futility? I chose to be loyal to a future self, in that case. But there is no doubt that betraying yourself in the now because you lack trust in your own brain is a shitty place to be.

The future

You have a life to recreate, and consequences to bear, but I have faith in you. It is not easy to be creative and highly intelligent in that bipolar way, because you will discover truths that other people can't see, and thus have to deal with the constant criticism of wrong people, sometimes very intelligent wrong people. You have been through this and are obviously strong, even if we couldn't see all that was going on.

Turn your natural abilities and your strength to curing yourself as best you can. What worked for me might work for you! I hope you try it and it does. But if you don't or if it doesn't then I think you will find a way. Study the drugs (many modern bipolar drugs are anti-convulsants, suggesting that what helps epilepsy might help bipolar). Study the physiology. You already know way more than I do. Look at plausible fringe theories (some interesting things to be found on the site I mentioned above). You will find something, and your life will get better.

My own apology

I hope you take this letter as I intend it: as an expression of care, sympathy, and of hope that perhaps what I have learned could help you in some way. Please forgive my boldness to speak to you personally when I don't know you, or all of what you are going through.

Most of all, I just want to say that I admire you for your openness, your willingness to admit to mistakes, and your commitment to change.

With love and encouragement,

Amber

---

Resources

Jim Phelps' Bipolar II site

Some papers that might be of use:

• The ketogenic diet may have mood-stabilizing properties. El-Mallakh RS, Paskitti ME. Med Hypotheses. 2001 Dec;57(6):724-6.
• The ketogenic diet; fatty acids, fatty acid-activated receptors and neurological disorders. Prostaglandins Leukot Essent Fatty Acids. 2004 Mar;70(3):253-64. Cullingford TE.
• Potential Applications of the Ketogenic Diet in Disorders Other Than Epilepsy Rif S. El-Mallakh Epilepsy and the Ketogenic Diet Nutrition and Health 2004, pp 153-159
• The neuropharmacology of the ketogenic diet. Pediatr Neurol. 2007 May;36(5):281-92. Hartman AL1, Gasior M, Vining EP, Rogawski MA.
• The neuroprotective properties of calorie restriction, the ketogenic diet, and ketone bodies. Brain Res Rev. 2009 Mar;59(2):293-315. doi: 10.1016/j.brainresrev.2008.09.002. Epub 2008 Sep 25. Maalouf M1, Rho JM, Mattson MP.
• Schizophrenia, gluten, and low-carbohydrate, ketogenic diets: a case report and review of the literature Nutr Metab (Lond). 2009; 6: 10. Bryan D Kraft and Eric C Westman
• The ketogenic diet for type II bipolar disorder. Neurocase. 2013;19(5):423-6. doi: 10.1080/13554794.2012.690421. Epub 2012 Oct 3. Phelps JR1, Siemers SV, El-Mallakh RS.