Thursday, 15 May 2014

What's the best diet?

Note: Any diet that's as risky as the classic ketogenic diet should only be used under the supervision of a trained and accredited dietitian (make sure when you go into their office you see some sort of degree in dietetics/nutrition on the wall somewhere, I am yet to see a health professional that doesn't have at least one of their degrees on at least one wall in their office). Plus, I don't care how obese somebody is, treat them with the same degree of respect you'd expect somebody to treat you with, or you're the one in need of a shrink, not them. I also italicise notes, brand names, Latin terms and other things that, by convention, should be italicised (like cis and trans) and bold important terms, in-text. 


What's the best diet? Well that's a good question that many of us encounter in our day-to-day lives. The ideal diet for weight loss would have to be one that's more easily sustainable, as if you hate your diet you're going to cheat on it a little at first, then a little more, then a little more, until you're no longer keeping to the diet at all. Despite this the best diet for long-term weight loss that's been proven effective in well-designed clinical trials is the ketogenic diet (KD) and perhaps one of its modern equivalents.1 Another benefit for this diet over other diets is that it's safe for diabetics and is associated with improved diabetes control and reduced risk of strokes and heart attacks.1 It's also associated with improved blood pressure control, compared to other weight-loss measures.2 But, this diet is NOT exactly palatable (i.e. tasty or for that matter, even tolerable-tasting, basically think an extremist version of the Atkins' diet) or risk-free. Unfortunately, it's well-known to cause constipation (mostly due to the lack of fibre), abdominal pain, diarrhoea, headache, weakness and malnutrition (don't worry, if you do use this diet vitamin/mineral supplements will work fine to replace prevent these deficiencies), amongst other problems.3 There's also a tremendous danger associated with the diet in certain people with genetic disorders such as acute porphyria, that might go undiagnosed all of somebody's life, provided they keep to the usual Australian/US diet. Talking to a shrink (psychologist) can also help you loose weight.4


Background on the ketogenic diet

Figure 1: Ketone bodies
The diet was originally developed circa 1920 for kids with epilepsy. The diet works by forcing the body to go into a state called ketosis, which is basically when the body burns fats for energy and a consequence of this is that you'll have an abnormally high amount of small molecules called ketone bodies (hence the "keto" prefix; my fellow students of the health professions might wish to note I'm not just calling them "ketones" because technically speaking one of them isn't one), floating around in your bloodstream. Ketone bodies are basically the fat equivalent to glucose, the body's preferred energy source that's derived from breaking down carbohydrates. See like glucose, ketone bodies are much more readily catabolised (broken down) to make energy than fatty acids as they're far simpler, chemically, and hence it's far simpler to turn them into the end products of fat catabolism in the body  energy, carbon dioxide and water.5,6

Most ketogenic diets do not pay attention to the specific types of fats being consumed. Different fatty acids have differing effects on cardiovascular (risk of strokes and heart attacks) and metabolic (i.e. relating to diabetes risk or control) risk. Diets high in saturated fats (any animal-derived fat will be high in saturated fat, except those found in fish) are associated with perhaps a slight (albeit so slight that most clinical trials have failed to demonstrate any clear effects as most trials aren't large enough to detect this slight difference) increase of cardiovascular and metabolic complications and an increased risk of prostate, breast and pancreatic cancers. Monounsaturated fats seem to reduce cardiovascular risk, ω-6 fats may increase cardiovascular risk and ω-3 fats reduce your risk of cardiovascular disease and cancer. 
ω-3/6s seem to have minimal effect on metabolic risk. Transunsaturated fats increase your risk of cardiovascular and metabolic events like strokes/heart attacks and diabetes mellitus ("sugar diabetes").7-24



Background

Figure 2: Cis-double bond
Fats are composed to three fatty acids chemically (covalently) bonded to glycerol, this conformation is also called a triglyceride. Fatty acids can be classified as saturated, polyunsaturated or monounsaturated, based on their chemistry. See saturated fatty acids, have no double bonds, which means they have as many hydrogen atoms to them as chemically possible, hence the adjective "saturated" as they're saturated with hydrogensMonounsaturated fatty acids have one double bond, which means they have two less hydrogen atoms as chemically possible for them to have. Hence, they are one (hence the "mono" prefix) carbon bond less saturated with hydrogens than the corresponding saturated fatty acid. Polyunsaturated fatty acids, have more than one (hence the "poly" prefix) double bond and are hence, significantly, less saturated than saturated fatty acids.


Figure 3: Trans-double bond
Another subset of fatty acids are the transunsaturated fatty acids (TSFAs) which are unsaturated fatty acids that are in the "trans" configuration. See all unsaturated fatty acids that occur in nature are in the "cis" configuration like in figure 2. But some TSFAs are produced, inadvertently, in the process of cooking (such as the vegetable oils used in fast foods). 
Figure 4: A diagram explaining the omega nomenclature

The omega (ω) nomenclature is basically where one lists how many carbons from the end (or "tail") of a fatty acid the first double bond appears; omega-3 fatty acids are ones in which the first double-bond occurs 3 carbons from the end of the fatty acid.



Some common natural fatty acids Note: ω is a Greek letter that's pronounced: "oh-m-eh-g-ah" and transliterated into English as "omega"
Essential fatty acids
α-linolenic acid (ALA; an ω-3 fatty
 acid). Found predominantly in plant
 oils. 
Linoleic acid (LLA; an ω-6 fatty acid). Found predominantly
in plant oils.
Conditionally essential fatty acids*
Docosahexaenoic acid (DHA; an
ω-3 fatty acid). Found
predominantly in fish oils. The body
is able to derive all of its requireme-
nts from ALA, except in cases of
severe deficiency. 
γ-linolenic acid (GLA; an
ω-6 fatty acid). Found
predominantly in plant oils.
Our GLA requirements can all be
synthesised from our dietary intake
of LLA.
ω-3 polyunsaturated fatty acids
Eicosapentaenoic acid (EPA). Found
predominantly in fish oils.  It can be
synthesised by our bodies from DHA.
ω-6 polyunsaturated fatty acids
Arachidonic acid (AA). Found predominantly in animal fats (not so much fish oils, red meat like pork is highest in arachidonic acid). Although even in animal fats its only found in traces (<5%). 
Dihomo‐γ‐linolenic acid. Found predominantly in vegetable oils
Omega-9 (monounsaturated) fatty acids
Oleic acid. Found predominantly in plant oils, especially, olive oil (the prefix, "ole" actually comes from the Latin name for olives - olea europaea).
Saturated fatty acids
Short-chain fatty acids (SCFAs). Acetic acid is found in small quantities (like 1%, weight-by-weight) in vinegars, butyric acid is present in small quantities in butter, the rest are usually synthesised as a by product of dietary fibre metabolism, by bacterial species living in one's large intestine. Only a small amount of fibre gets converted to SCFAs and unlike LCSFAs they're actually generally good for you. 
Long-chain saturated fatty acids (LCFAs). Found in most meats, especially red meat and chicken's skin, but also palm oil, butter, milk, cream and cheese. 

* These are ones that are essential in certain conditions, such as during infancy.



It was discovered when doctors desperate to control their patient's epilepsy that had resisted all the current drug treatment (which was a class of a really toxic anti-seizure drugs called the bromides, that were deadly even in slight overdoses. There was a then "modern" development called phenobarbital, but it's also toxic in even the slightest overdose and only had efficacy in one subtype of epilepsy) tried an old treatment discovered by Greek physicians thousands of years ago (circa 500 BC); fasting. They noticed a significant improvement in their patients' seizure control within a week. They, of course, realised the fact that they couldn't go on indefinitely starving their patients so they gradually re-introduced individual parts of the kids' diets, as a controlled experiment to determine what, specifically, they needed to deprive the kids of in order to produce seizure control and they found that carbohydrates were, indeed, the answer.26,27


Nowadays, this treatment is reserved as a last resort treatment for epilepsy that hasn't responded to drugs and surgery and quite frankly do you blame the doctors for reserving it this position? This diet is so unnatural for the body that you in effect have to feed the person a diet that's so nutritionally deficient that it's not only unpalatable but that causes severe constipation in a number of kids and vitamin/mineral deficiencies if not taken with vitamin/mineral supplements.27


Part of the reason for this is the fact that dietary fibre, is a form of carbohydrate and fibre's primary job in the human body is to provide some "roughage" for your digestive tract, giving your stools greater volume. Without it you basically having little to defecate, hence the constipation seen in those on low-fibre diets like cKD. Those of you that read the entry in my table above about SCFAs, produced in the large intestine from fibre might be thinking, "Well then fibre must be conducive to the ketogenic diet." Well it isn't, thanks to a little bit of human physiology called gluconeogenesis (GNG).26


Gluconeogenesis, is a term you can actually figure out the meaning of, simply by breaking up the parts of its name. It means the production (hence "genesis") of glucose (hence the "gluco") from small molecules other than carbohydrates (which are basically glucose or other sugar molecules chemically bound together in a very large structure, usually. Hence the "neo" as in "neo-nazi" which means "new" or "from scratch"). One of those small molecules is propionic acid, one of the chief SCFAs produced in response to dietary fibre. Gluconeogenesis is also important in those with type II diabetes mellitus (T2DM), as they have like three times as much GNG occurring in their livers than most people. This is actually why the drug metformin is usually the best first-line treatment for people with T2DM, as it reduces GNG, amongst other more recently discovered actions.27


Glycaemic indices (GIs) are basically a way of objectively measuring how much of a rise in blood sugar ("glucose") occurs immediate after eating the food for which the GI is assigned. It's usually given as a decimal number, between 0 and 1, although it can also be represented as a percentage out of 100. Whereas 50% (or 0.5) indicates, that if you eat the food for which this GI is assigned it'll produce half the increase in blood sugar that eating an equivalent mass of pure glucose would cause. By the way, the refined sugar we generally call "sugar" has a GI of 55%, as it's 50% fructose, 50% glucose (as it's sucrose, which is these two sugars chemically bonded together) and fructose is very slowly converted to glucose in the body (which is why foods loaded in fructose, like fruit and yoghurt, have a low GI, despite being loaded with sugar).28



Modern equivalents

The classic ketogenic diet (cKD) is, by definition (as this is the only way to induce ketosis, as the body will relentlessly favour glucose as an on-demand energy source over ketone bodies), an incredibly low carbohydrate diet, low-moderate protein and high-fat diet and what this means for patients is that the diet consists almost solely of high-fat, low/medium-protein foods like butter and cream. As this diet is so restrictive a few modern equivalents (only really equivalent in their ability to prevent seizures in people with epilepsy and even that equivalence is fairly scratchy) have been thought up (abbreviated mKDs; like the modified Atkins', medium chain triglyceride [MCT] and low glycaemic index [LGI] diets), although their efficacy in achieving weight loss is significantly different from that of the KD.

The evidence supporting the Atkins' diet for weight loss is mixed  some clinical trials, show efficacy (usually modest), whereas others show no efficacy, or intolerable side effects (like clogged arteries which put you at an increased risk of heart attacks/strokes). Usually Atkins or similarly low-carbohydrate diets (like the cKD) produce the most profound weight loss in the short-term (by short-term I mean <6 months), in the long-term most weight loss diets are usually about equal, although there might be small tendencies favouring extremely low carbohydrate diets like cKD. The MCT diet, is significantly more relaxed than the other mKDs, as the use of MCTs is more efficient in causing the body to undergo ketosis, the evidence supporting its use in people with obesity is pretty much non-existent as it's really just used to treat epilepsy. It also has some unpleasant side effects such as diarrhoea and abdominal pain. The LGI diet is effective for weight loss, according to a number of different studies and is pretty much the only mKD that's proven itself effective for weight loss in well-designed trials.29



Alternatives

Alternative weight loss diets for which the evidence to support is good quality and strong include:29
  • Low fat diets (tend to be less effective than low carbohydrate diets)
  • High-protein diets, this is one I want to make it very clear, see a dietitian before starting it as it can kill you if you have poor kidney function, which can be asymptomatic (i.e. without symptoms) in some people. There's also a few genetic disorders that can make this very dangerous. These diets also increase your risk of kidney stones. 
  • High-fibre diets. Might also reduce your risk colorectal cancer as fibre has positive effects on the bowels. This is probably why Vegetarians have a low risk of colorectal cancer. If you have chronic constipation problems this is probably preferable for previously mentioned reasons.30
Exercising is always a good idea, if you want to exercise to loose weight as well as diet I'd advise high-protein diets (after taking the necessary precautions, though) or low glycaemic index diets, as many of the other weight loss diets have the side effect of making you feel more tired than usual, especially when you're just starting on them. Exercise also reduces your risk of complications of obesity like heart disease or diabetes mellitus. There's also some evidence (albeit weak), that it might improve mood. I say weak as it's impossible to perform a controlled experiment with exercise, as it's impossible to give somebody a placebo walk, run, jog or lifting weights. Another thing that it's impossible to control for when it comes to clinical trials is the fact that loosing weight also improves your self-esteem and body-image, so it's possible these people just felt better because they looked better.31,32

Medication, can also help. I personally think they're pretty useless, that is, medications, for weight loss. While they can increase weight loss a little bit (like a couple of kilos), if used in conjunction to exercise and dietary changes, they tend to cause pretty minimal benefit. Mostly, because many weight loss drugs are latter taken off the market due to their unacceptable safety issues (like sibutramine (Reductil; caused heart attacks/strokes), fenfluramine (in "Fen-phen"; caused heart problems), rimonabant (Acomplia; caused suicidal thoughts)) and their efficacy is limited at best. Usually, in clinical trials, they cause like at most (and this is exceptionally rare as far as this sort of extent of weight loss) 3 kilogram reductions, on average, in the long-term. Currently available medications include:

  • Orlistat (Xenical, Zurical); this one is the safest one so far. It's been used for like a decade or so and still no major safety issues have popped up. It works by inhibiting the uptake of fats by the body. Basically meaning you defecate the fat in your food. I should mention it only works on fats, not carbohydrates, and even there it isn't perfect. In a study comparing the cKD with low-fat & orlistat-assisted diet, they found there was no difference in weight loss between the groups but the cKD was associated with better blood pressure control. It is available over-the-counter. I should mention here and now, because I've heard of pharmacists not having the stomach to mention one of its less glamorous side effects, it can cause anal leakage, oily stools, headaches, fatigue and diarrhoea and these are just the common side effects!27

  • Lorcaserin (Belviq); this one is only available in the U.S. so far. It's one I think is more dangerous than its predecessors because it works by activating the 5-HT2C receptors, which are serotonin receptors found in the brain and their roles include regulating body temperature, blood pressure, mood and other essential house-keeping functions in the body. It works by suppressing appetite. Studies so far have shown a lower incidence of side effects, with fewer patients discontinuing due to side effects, but lorcaserin has caused a few cases of serotonin syndrome which is a potentially fatal side effect caused by excessive stimulation of the 5-HT2C receptors (or other serotonin receptors) that's characterised by disturbed house-keeping functions in the body, like raised body temperature, changes in mood, hallucinations, diarrhoea, excessive sweating (disproportionate to surrounding temperature, or activity [like exercise]), dizziness, nausea, shivering, high blood pressure, high heart rate, headache, shivering, coma and tremor. I should mention, try to not self-diagnose where possible, if you do take this medication and fear you might have it, see a doctor. See you can't be objective about your own body, a doctor can be objective about your body. In the U.S. lorcaserin and orlistat are the only drugs that are approved for long-term use as treatments for obesity.33-36

    Another problem I think might pop up with this drug is that it might cause heart problems as a closely related receptor to 5-HT2C, like it's next-door neighbour in effect, 5-HT2B, is weakly bound by the drug and this receptor is implicated in the heart problems fenfluramine can cause.33-36

  • Phentermine (Duromine, Metermine); this one has also been used for decades so its safety record is pretty positive (it was in "fen-phen" but it was the fenfluramine component that caused the heart problems). It also works by suppressing appetite and increasing the expenditure, by the body, on energy-consuming processes in the body. More specifically, it works by causing a cascading release of noradrenaline in the body, one of the "fight or flight" hormones. Common side effects include:27
    • Sleeplessness
    • Restlessness
    • Nervousness
    • Feeling "high"
    • Agitation
    • Irregular heart rhythm
    • High heart rate
    • High blood pressure
    • Diarrhoea




  • Vomiting



  • Headache



  • Rash



  • Urinating a lot



  • Swelling of the face



  • Unpleasant taste



  • Hives



  • Impotence
  • Certain antidepressants (note many of these drugs can be used for a heap of other things besides relieving depression) like venlafaxine (Effexor, Efexor), duloxetine (Cymbalta), milnacipran (Ixel, Savella, Joncia), fluoxetine (Prozac), sertraline (Lustral, Zoloft) and bupropion (Prexatan, Zyban; normally used to help people quit smoking in Australia and the U.K.) can produce weight loss. Fluoxetine and sertraline-induced weight loss is usually temporary and modest (like less than a kilogram is the average). Plus some people have the opposite reaction to fluoxetine and sertraline and gain weight, especially with fluoxetine. Bupropion is actually being developed, in combination with naltrexone (an anti-addictive drug used traditionally to treat heroin addicts), as a stand-alone (i.e. this being this combination's only medical use) treatment for obesity. Their most common side effects are insomnia, headache, dizziness and digestive complaints (like nausea, vomiting, diarrhoea, etc.).27 

  • Certain anticonvulsants (anti-seizure medications) can induce weight loss (although most do the reverse), especially topiramate (Epiramax, Tamate, Topamaxand zonisamide (Zonegran), both of which are currently being developed, in combination with other drugs (phentermine and bupropion, respectively) as a stand-alone treatment for obesity. They have significant safety issues, they both cause short-term impairment in memory and concentration, psychiatric problems (like depression, suicidal thoughts, anxiety, hallucinations, etc.) and they both can (albeit rarely) cause blood cell abnormalities which can be fatal if not caught early, they can both cause digestive complaints (their most common side effects), headaches, dizziness, etc. They can also cause metabolic acidosis (which is when your blood becomes too acidic; which can be fatal) and with long-term use, brittle bones (more prone to breaks) and kidney stones.27 


The supplement acetyl-L-carnitine (ALC), may improve the efficiency of cKD in causing ketosis. As it ALC is like a supercharger of fat metabolism.37

References:

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