Category Archives: Nutrients - Page 7

Answer Day: What Causes High LDL on Low-Carb Paleo?

Posted by on March 3, 2011 383 comments

First, thank you to everyone who commented on the quiz. I enjoyed reading your thoughts.

Is High LDL Something to Worry About?

Perhaps this ought to be the first question. Jack Kronk says “I don’t believe that high LDL is necessarily a problem” and Poisonguy writes “Treat the symptoms, Larry, not the numbers.” Poisonguy’s comment assumes that the LDL number is not a symptom of trouble. Is it?

I think so. It helps to know a little about the biology of cholesterol and of blood vessels.

When cells in culture plates are separated from their neighbors and need to move, they make a lot of cholesterol and transport it to their membranes. When cells find good neighbors and settle down, they stop producing cholesterol.

The same thing happens in the body. Any time there is a wound or injury that needs to be healed, cholesterol production gets jacked up.

When people have widespread vascular injuries, cholesterol is produced in large quantities by cells lining blood vessels. Now, to repair injuries cells have to coordinate their functions. Endothelial cells are the coordinators of vascular repair: they direct other cell types, like smooth muscle cells and fibroblasts, in the healing of vascular injuries.

To heal vascular injuries, these cells not only need more cholesterol for movement; they also need to multiply. It turns out that LDL, which carries cholesterol, also causes vascular cells to reproduce (“mitogenesis”):

The best-characterized function of LDLs is to deliver cholesterol to cells. They may, however, have functions in addition to transporting cholesterol. For example, they seem to produce a mitogenic effect on endothelial cells, smooth muscle cells, and fibroblasts, and induce growth-factor production, chemotaxis, cell proliferation, and cytotoxicity (3). Moreover, an increase of LDL plasma concentration, which is observed during the development of atherosclerosis, can activate various mitogen-activated protein kinase (MAPK) pathways …

We also show … LDL-induced fibroblast spreading … [1]

If endothelial cells are the coordinators of vascular repair, and LDL particles their messengers to fibroblasts and smooth muscle cells, then ECs should be able to generate LDL particles locally. Guess what:  ECs make a lipase whose main effect is to decrease HDL levels but can also convert VLDL and IDL particles into LDL particles and remove fat from LDL particles to make them into small, dense LDL:

Endothelial lipase (EL) has recently been identified as a new member of the triglyceride lipase gene family. EL shares a relatively high degree of homology with lipoprotein lipase and hepatic lipase …

In vitro, EL has hydrolyzed phospholipids in chylomicrons, very low density lipoprotein (VLDL), intermediate density lipoprotein and LDL. [2]

Immune cells, of course, are essential for wound healing and they should be attracted to any site of vascular injury. It turns out that immune cells have LDL receptors and these receptors may help them congregate at sites of vascular injury. [3]

I don’t want to exaggerate the state of the literature here:  this is a surprisingly poorly investigated area. But I believe these things:

1.      Cholesterol and LDL particles are part of the vascular wound repair process.

2.      Very high LDL levels are a marker of widespread vascular injury.

Now this is not the “lipid hypothesis.” Compare the two views:

  • The lipid hypothesis:  LDL cholesterol causes vascular injury.
  • My view:  LDL cholesterol is the ambulance crew that arrives at the scene of the crime to help the victims. The lipid hypothesis is the view that ambulance drivers should be arrested for homicide because they are commonly found at murder scenes.

So, to Poisonguy, on my view high LDL numbers are a symptom of vascular injury and are a cause for concern.

Big-Picture View of the Cause of High LDL

So, on a micro-level, I think vascular damage causes high LDL. But what causes vascular damage?

Here I notice a striking difference in commenters’ perspectives and mine. I tend to take a big-picture, top-down view of biology. There are three basic causes of nearly all pathologies:

1.      Toxins, usually food toxins.

2.      Malnutrition.

3.      Pathogens.

The whole organization of our book is dictated by this view. It is organized in four Steps. Step One is about re-orienting people’s views of macronutrients away from high-grain, fat-phobic, vegetable-oil-rich diets toward diets rich in animal fats. The other steps are about removing the causes of disease:

1.      Step Two is “Eat Paleo, Not Toxic” – remove food toxins.

2.      Step Three is “Be Well Nourished” – eliminate malnutrition.

3.      Step Four is “Heal and Prevent Disease” – address pathogens by enhancing immunity and, where appropriate, taking advantage of antibiotic therapies.

So when someone offers a pathology, any pathology, my first question is: Which cause is behind this, and which step do they need to focus on?

In Larry’s case, he had been eating low-carb Paleo for years. So toxins were not a problem.

Pathogens might be a problem – after all, he’s 64, and everybody collects chronic infections which tend to grow increasingly severe with age – but Larry hadn’t reported any other symptoms. More to the point, low-carb Paleo diets typically enhance immunity, yet Larry had fine LDL numbers before adopting low-carb Paleo and then his LDL got worse. So it wouldn’t be infectious in origin unless his diet had suppressed immunity through malnutrition – in which case the first step would be to address the malnutrition.

Step Three, malnutrition, was the only logical answer. The conversion to Paleo removes a lot of foods from the diet and could easily have removed the primary sources of some micronutrients.

So I was immediately convinced, just from the time-course of the pathology, that the cause was malnutrition.

Micronutrient Deficiencies are Very Common

In the book (Step Three) we explain why nearly everyone is deficient in micronutrients. The problems are most severe for minerals:  water treatment removes minerals from water, and mineral depletion of soil by industrial agriculture leads to mineral deficiencies in farmed plants and grain-fed animals.

This is why our “essential supplements” include a multimineral supplement plus additional quantities of five minerals – magnesium, copper, chromium, iodine, and selenium. Vitamins get a lot of attention, but minerals are where the big health gains are.

Copper Deficiency and LDL

Some micronutrient deficiencies are known to cause elevated LDL.

Readers of our book know that copper causes vascular disease; blog readers may be more familiar with an excellent post by Stephan, “Copper and Cardiovascular Disease”, discussing evidence that copper deficiency causes cardiovascular disease. As I’ve just argued that cardiovascular disease causes high LDL, it shouldn’t be a surprise that copper deficiency also causes hypercholesterolemia:

Copper and iron are essential nutrients in human physiology as their importance is linked to their role as cofactors of many redox enzymes involved in a wide range of biological processes, as well as in oxygen and electron transport. Mild dietary deficiencies of both metals … may cause long-term deleterious effects in cardiovascular system and alterations in lipid metabolism (3)….

Several studies showed a clear correlation among copper deficiency and dyslipidemia. The main alterations concern higher plasma CL and triglyceride (TG) concentrations, increased VLDL-LDL to HDL lipoproteins ratio, and the shape alteration of HDL lipoproteins.  [4]

The essentiality of copper (Cu) in humans is demonstrated by various clinical features associated with deficiency, such as anaemia, hypercholesterolaemia and bone malformations. [5]

Over the last couple of decades, dietary copper deficiency has been shown to cause a variety of metabolic changes, including hypercholesterolemia, hypertriglyceridemia, hypertension, and glucose intolerance. [6]

Copper deficiency is, I believe, the single most likely cause of elevated LDL on low-carb Paleo diets. The solution is to eat beef liver or supplement.

So, was my advice to Larry to supplement copper?  Yes, but that was not my only advice.

Other Micronutrient Deficiencies and Elevated LDL

Another common micronutrient deficiency that causes elevated LDL cholesterol is choline deficiency that is NOT accompanied by methionine deficiency. That is discussed in my post “Choline Deficiency and Plant Oil Induced Diabetes”:

Choline deficiency (CD) by itself induces metabolic syndrome (indicated by insulin resistance and elevated serum triglycerides and cholesterol) and obesity.

A combined methionine and choline deficiency (MCD) actually causes weight loss and reduces serum triglycerides and cholesterol …

I quote both these effects because it illustrates the complexity of nutrition. A deficiency of a micronutrient can present with totally different symptoms depending on the status of other micronutrients.

Julianne had a really nice comment, unfortunately caught in the spam filter for a while, with a number of links. She mentions vitamin C deficiency and, with other commenters, noted the link between hypothyroidism and elevated LDL. As one cause of hypothyroidism is iodine or selenium deficiency, this is another pathway by which mineral deficiencies can elevate LDL.

UPDATE: Mike Gruber reduced his LDL by 200 mg/dl by supplementing iodine. Clearly iodine can have big effects!

Other commenters brought up fish oil. They may be interested to know that fish oil not only balances omega-6 to modulate inflammatory pathways, it also suppresses endothelial lipase and thus moderates the LDL-raising and HDL-lowering effect of vascular damage:

On the other hand, physical exercise and fish oil (a rich source of eicosapentaenoic acid and docosahexaenoic acid) suppress the activity of EL and this, in turn, enhances the plasma concentrations of HDL cholesterol. [7]

Whether this effect is always desirable is a topic for another day.

My December Advice to Larry

So what was my December advice to Larry?

It was simple. In adopting a low-carb Paleo diet, he had implemented Steps One and Two of our book. My advice was to implement Step Three (“Be well nourished”) by taking our recommended supplements. Eating egg yolks and beef liver for copper and choline is a good idea too.

Just to cover all bases, I advised to include most of our “therapeutic supplements” as well as all the “essential supplements.”

Since December, Larry has been taking all the recommended supplements and eating 5 ounces per week of beef liver. As I noted yesterday, Larry’s LDL decreased from 295 mg/dl to 213 mg/dl, HDL rose from 74 mg/dl to 92 mg/dl, and triglycerides fell from 102 to 76 mg/dl since he started Step Three. This is all consistent with a healthier vasculature and reduced production of endothelial lipase.

Conclusion

Some people think there is something wrong with a diet if supplements are recommended. They believe that a well-designed diet should provide sufficient nutrition from food alone, and that if supplements are advised then the diet must be flawed.

I think this is quite mistaken. The reality is that Paleolithic man was often mildly malnourished, and modern man – due to the absence of minerals from treated water and agriculturally produced food, and the reduced diversity and higher caloric density of our foods – is severely malnourished compared to Paleolithic man.

We recommend eating a micronutrient-rich diet, including nourishing foods like egg yolks, liver, bone broth soups, seaweed, fermented vegetables, and so forth. But I think it’s only prudent to acknowledge and compensate for the widespread nutrient depletion that is so prevalent today. Even when nutrient-rich food is regularly eaten, micronutrient deficiencies are still possible.

Eating Paleo-style is not enough to guarantee perfect health. Luckily, supplementation of the key nutrients that we need for health and that are often missing from foods will often get us the rest of the way.

References

[1] Dobreva I et al. LDLs induce fibroblast spreading independently of the LDL receptor via activation of the p38 MAPK pathway. J Lipid Res. 2003 Dec;44(12):2382-90. http://pmid.us/12951358.

[2] Paradis ME, Lamarche B. Endothelial lipase: its role in cardiovascular disease. Can J Cardiol. 2006 Feb;22 Suppl B:31B-34B. http://pmid.us/16498510.

[3] Giulian D et al. The role of mononuclear phagocytes in wound healing after traumatic injury to adult mammalian brain. J Neurosci. 1989 Dec;9(12):4416-29. http://pmid.us/2480402.

[4] Tosco A et al. Molecular bases of copper and iron deficiency-associated dyslipidemia: a microarray analysis of the rat intestinal transcriptome. Genes Nutr. 2010 Mar;5(1):1-8. http://pmid.us/19821111.

[5] Harvey LJ, McArdle HJ. Biomarkers of copper status: a brief update. Br J Nutr. 2008 Jun;99 Suppl 3:S10-3. http://pmid.us/18598583.

[6] Aliabadi H. A deleterious interaction between copper deficiency and sugar ingestion may be the missing link in heart disease. Med Hypotheses. 2008;70(6):1163-6. http://pmid.us/18178013.

[7] Das UN. Long-chain polyunsaturated fatty acids, endothelial lipase and atherosclerosis. Prostaglandins Leukot Essent Fatty Acids. 2005 Mar;72(3):173-9. http://pmid.us/15664301.

Low-Protein Leanness, Melanesians, and Hara Hachi Bu

Posted by on January 27, 2011 71 comments

Gunther gatherer raised an interesting issue in a comment to Tuesday’s post.  Protein may be satiating in the short run; but what about the long run?

[H]igh protein keeps you full at first. But no one really knows for how long. Eventually it stops working and you find you’re eating a lot ON TOP of all the high protein you were already eating. All of us here tried Atkins long ago and fell off the bandwagon more than enough times to know it gets boring, stops working against hunger and doesn’t keep the fat off forever.

I agree. This is why we recommend a version of the normal Perfect Health Diet, which is normal — not high — in protein, for weight loss. Our diet isn’t the quickest way to lose weight, but we think it is likely to work best in the long run.

The Long-Term Effects of High-Protein Diets

I argued in Tuesday’s post that the satiating effects of protein had to be temporary, and that in the long run higher protein might cause, not reduced appetite, but only a slight change toward a leaner body composition.

A more interesting question is:  could high-protein diets be positively harmful?

Maybe!  Studies in both animals and humans indicate that eating high protein during childhood creates a predisposition for obesity in later life.

For instance, rats raised on a high-protein diet in childhood are more likely to become obese when given calorie-rich (sugar and fat) diets in adulthood. [1] The researchers conclude:

Our research demonstrating a significant susceptibility to an obese phenotype in rats weaned onto a high-protein diet and then challenged in adulthood with a high-fat high-sucrose diet suggests that lasting changes result from altering the composition of the first solid food that is consumed throughout growth into early adulthood. While all rats in this study consumed the same high energy diet during the last 6 weeks of the intervention, distinct metabolic profiles remained evident from exposure to the different diets during growth. This would suggest that these changes, either long-lasting or perhaps permanent, ultimately influenced the adiposity response of these rats to a high energy challenge in adulthood. Overall, it appears that a long-term diet high in protein, when mismatched with a high energy challenge, has negative effects on body mass and hormones and genes involved in glucose and lipid metabolism. [1]

The same phenomenon occurs in humans. In the book we mentioned a study showing that slightly higher protein level in infant formula – 9% protein vs 7% normally – caused children to become overweight two years later. [2]

So parents, let your kids follow their taste buds to high-carb, high-fat diets!

Might adult high protein diets promote later-life obesity too? I’m not aware of evidence, but I don’t think the possibility can be ruled out. I will look for evidence when I do research for two future blog series: one on protein intake, aging, and longevity; the other on connections between obesity and the human aging program.

Can You Be Lean on a Low-Protein Diet?

Tuesday’s post cited research indicating that we have a set point for protein intake: humans are genetically programmed to seek around 360 protein calories per day, and appetite becomes satiated once that is achieved.

But if protein intake determines appetite, then it seems those eating a low-protein diet face a Hobson’s choice:

  • If total calories are not increased, then the low protein dieter can expect to have a chronically unsatisfied appetite.
  • If total calories are increased, so that appetite is satisfied, then the low protein dieter can expect a higher equilibrium weight and a slightly less lean body.

Is it possible, then, to restrict protein, eat mostly carbs and fat which we know are the ingredients of appetizing desserts – and still achieve a lean healthy body, and feel comfortable? 

Yes, I believe so.

Melanesians Do It

Gunther pointed out that Melanesians are lean and long-lived on low protein diets:

I think it would be a bit fairer to include some consideration and explanation of Melanesians and their extremely low protein diet (anywhere from 10% to only 3% protein daily). Their extremely high level fitness and body composition flies in the face of all of these high protein studies.

It’s true: Kitavans, Tokelauans, and other Melanesians eat high-carb and low-protein, yet they’re noted for “extreme leanness.” [3] Why?

Well, first of all, the Melanesian islander diet is a variant of the Perfect Health Diet:  it is entirely free of food toxins. As I argued last week, eliminating toxins is the key to healthy weight regulation. But there are other factors.

Coconut Oil

The most abundant fatty acid in the diets of Kitavans and Tokelauans is lauric acid, the 12-carbon fatty acid which is the predominant fatty acid in coconut oil. [4, 5] These shorter-chain fatty acids are ketogenic and have significant effects on the body: for instance, they raise HDL levels. They also make people lean.

In one study, 8 weeks taking 1 tbsp per day coconut oil caused a significant decrease in body weight, waist size, and blood triglycerides. [6] In another, obese women who received 2 tbsp (30 ml) coconut oil per day slimmed their waist and increased HDL without an increase in LDL, while a comparison group receiving soybean oil did not slim their waist and had lower HDL with higher LDL and total cholesterol. [7]

Resistant Starch

Another feature of the Melanesian diet is that the biggest share of calories came from “safe starches” like yams, sweet potatoes, and sago.

These foods have a lot of fiber in the form of “resistant starch.” Digestion of resistant starch by colonic bacteria produces a lot of butyrate, a short-chain fatty acid that strongly promotes leanness.

For example, butyrate improves insulin sensitivity and prevents rats from becoming obese. [8]

Hara Hachi Bu

But the most reliable strategy seems to have been worked out by Asian and Pacific cultures long ago, many thousands of years ago.

The key is that if the diet is well nourishing, then appetite will be mild and easy to consciously control. What will be experienced is not hunger, which indicates malnourishment, but a mild desire for food that can easily be ignored.

There is an ancient Chinese saying:

“Eat until you are eight-tenths full, walk 100 steps after meals, live 99 years.”

In Japanese the saying is Hara Hachi Bu, eat until eight-tenths full. Hara Hachi Bu is common practice in Okinawa, where it helped produce the world’s most long-lived population.

As we note in the book, the traditional Okinawan diet is extremely close to the Perfect Health Diet: the Okinawan diet was rich in safe starches and animal fats, and near the low end of our recommended protein range: Okinawans ate about 300 g (2/3 pound) meat and fish per day.

The key here is that on a low-protein diet, eating until eight-tenths full is not a calorie-restricted diet. It is a calorie-sufficient diet that isn’t quite satiating because it is low in protein.

Intermittent fasting is a helpful part of Hara Hachi Bu. Eating only within a relatively short window each day makes it easy to keep calories down.

My Experience

I have been practicing protein restriction for several years, eating coconut oil and safe starches for several years, and practicing daily intermittent fasting for over six months. I drink tea or lemon-flavored water through the morning, and on most days eat only between 2 pm and 8 pm. If I snack during the fast it is usually either a piece of dark chocolate or some coconut oil.

I sometimes go many days eating relatively little, then eat a lot for a few days. Physical activity – sports, intense exercise, running – increases my appetite noticeably. Regardless, I never feel hungry. It is easy to complete the daily fast: some tea, sometimes with coconut oil or dark chocolate, is enough. I now do total fasting on religious fast days – for instance, I now do a 64-hour fast from Holy Thursday through Easter Sunday morning. Generally, as soon as I focus my attention on work I forget that I wanted food.

(This is a very good sign for my health, by the way. During my long chronic illness I couldn’t tolerate fasting at all.)

I haven’t noticed difficulty adding muscle when I work out. I believe I would add muscle more easily on a higher-protein diet, but as it is I add muscle more easily than I used to on the standard American diet. I’m content with my body composition.

Conclusion

I am convinced that by eating coconut oil, getting carbs from safe starches, and practicing intermittent fasting and Hara Hachi Bu, most people can become well-muscled and lean on a low-protein diet without any sense of hardship.

Since a carb-fat mix is the classic recipe for dessert, this makes for an extremely tasty diet.

If you want the surest way to lose weight over the next few days, eat a high-protein diet. But if you want a long-term diet that maximizes longevity by restricting protein, consider eating a tablespoon or two of coconut oil per day, fasting for 16 hours a day, and finishing your meal eight-tenths full.  

If you walk a hundred steps after dinner, you just might become a healthy centenarian!

References

[1] Maurer AD et al. Consumption of diets high in prebiotic fiber or protein during growth influences the response to a high fat and sucrose diet in adulthood in rats. Nutr Metab (Lond). 2010 Sep 29;7:77. http://pmid.us/20920272.

[2] European Childhood Obesity Trial Study Group. Lower protein in infant formula is associated with lower weight up to age 2 y: a randomized clinical trial. Am J Clin Nutr. 2009 Jun;89(6):1836-45. http://pmid.us/19386747.

[3] Lindeberg S et al. Haemostatic variables in Pacific Islanders apparently free from stroke and ischaemic heart disease–the Kitava Study. Thromb Haemost. 1997 Jan;77(1):94-8. http://pmid.us/9031456.

[4] Lindeberg S et al. Lipoprotein composition and serum cholesterol ester fatty acids in nonwesternized Melanesians. Lipids. 1996 Feb;31(2):153-8. http://pmid.us/8835402.

[5] Lindeberg S, Vessby B. Fatty acid composition of cholesterol esters and serum tocopherols in Melanesians apparently free from cardiovascular disease – the Kitava study. Nutr Metab Cardiovasc Dis. 1995; 5: 45-53.

[6] Xue C et al. Consumption of medium- and long-chain triacylglycerols decreases body fat and blood triglyceride in Chinese hypertriglyceridemic subjects. Eur J Clin Nutr. 2009 Jul;63(7):879-86. http://pmid.us/19156155.

[7] Assunção ML et al. Effects of dietary coconut oil on the biochemical and anthropometric profiles of women presenting abdominal obesity.  Lipids. 2009 Jul;44(7):593-601. http://pmid.us/19437058.

[8] Gao Z et al. Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes. 2009 Jul;58(7):1509-17. http://pmid.us/19366864.

Protein, Satiety, and Body Composition

Posted by on January 25, 2011 62 comments

A number of studies have found protein to be the most satiating macronutrient, with fat moderately satiating, and carbs least satiating.

Thus, when people reduce carbs and increase protein, their appetite declines and they almost always reduce calorie intake. This can leads to rapid short-term weight loss. This is why most popular weight loss diets are high in protein: increasing protein causes dieters to quickly lose some weight, encouraging them to continue.

A 2005 editorial in the American Journal of Clinical Nutrition summarized the evidence that higher protein intake is helpful for weight loss:

The higher than usually recommended protein content of many popular diets, such as the Atkins Diet, The Zone, and The South Beach Diet, seems to point at possible solutions to the obesity epidemic. Many national dietary guidelines have, until recently, recommended that only 10–20% of the calorie content of the diet come from protein; however, 30–40% of the calorie content in the aforementioned diets comes from protein, at the expense of carbohydrates. Newer research indicates that the high-protein content of these diets may actually be the reason for their partial success in inducing weight loss, despite no restrictions in total calories (2)….

In this issue of the Journal, Weigle et al (3) showed that an increase in dietary protein from 15% to 30% of energy and a reduction in fat from 35% to 20%, at a constant carbohydrate intake, produces a sustained decrease in ad libitum calorie intake and results in significant weight loss….

Weigle et al’s results clearly showed that protein is more satiating than is fat, and previous studies have shown that protein is more satiating than is carbohydrate (4). Moreover, diets with a fat content fixed at 30% of calories produce more weight loss when high in protein (25% of energy) than when normal in protein (12% of energy): 9.4 compared with 5.9 kg after 6 mo; after 1 y, evidence was found to suggest that the high-protein diet, independent of the loss of total body fat, resulted in a significant loss of visceral fat (5). [1]

But there are downsides to high protein consumption. Various animal experiments have found that longevity is increased with protein restriction. Also, protein restriction promotes autophagy, which enhances immunity to intracellular bacteria and viruses. So higher protein intake may shorten lifespan and increase the risk of disease.

In a post on his blog (linked in this comment), Dennis Mangan introduced us to the “protein leverage hypothesis.” This hypothesis is put forward in a 2005 paper by SJ Simpson of Oxford University and D Raubenheimer of the University of Auckland [2].

The Satiating Power of Protein

The paper has some graphs which neatly illustrate the satiating power of protein. When animals are given a food formula with a lower protein fraction, they eat more total calories.

Here are some data from rats (b) and chickens (c). The numbers are in kiloJoules; divide by 4.18 to get calories. The animals were on feed formulas with a constant fat content, but different carb-protein ratios. Each data point represents a diet with a different P:C ratio.

If both macronutrients were equally satiating, then the animals would eat the same amount of calories regardless of their food’s protein-carb ratio. The data points would fall on a 45º line (say, for chickens, a constant 1000-kJ line connecting the 1000 kJ mark on the y-axis with the 1000 kJ mark on the x-axis).

But they don’t:  if a line were fitted to these points, it would be much closer to vertical than 45º. The rats, for instance, eat around 150 kJ protein and 75 kJ carb if given high-protein food, but 75kJ protein and 300 KJ carb if given high-carb food. That’s 225 kJ (54 calories) on a high-protein diet, but 375 kJ (90 calories) on a high-carb diet.

The chickens and rats act like protein dominates appetite control:

  • A shortage of protein makes them hungry, and it takes a lot of carbohydrate to satisfy that hunger. So they eat a calorie excess.
  • An excess of protein satisfies their hunger and causes them to quit eating while they are still in calorie deficit.

Evidence in Humans

The same sort of thing happens in humans:

Results a, b, and c are from “short-term” experiments that varied from 2 days to 6 months in length. Results d, e, f, and g are from “long-term” experiments.

People tend to gravitate toward a protein intake of 1520 kJ (360 calories). This can be construed as the “normal” human protein intake, and tends to occur near a carb+fat intake of 8000 kJ (1900 calories). So the “normal” protein fraction of the diet is 360/2260 or 16%. This is consistent with epidemiological data, which finds that nearly everyone worldwide eats near 15% protein.

A line fit to the data has the same steep slope as the animal experiments, but note something interesting. The short-term experiments have a very steep slope, but the long-term experiments have a slope much closer to 45º.

This has to happen. Otherwise, a high-protein diet would lead to permanent calorie deficit which, over time, would lead to starvation. A low-protein diet would lead to permanent calorie excess which, over time, would lead to obesity.

Since we know people neither starve nor become obese due to small adjustments in protein fraction, they must adjust their calorie intake. In the long run, protein no longer controls calorie intake. So there is great protein leverage in the short-term, but much less protein leverage in the long term.

Simpson and Raubenheimer try to develop protein leverage into a theory of obesity. It’s not a very good theory, so I’ve relegated it to an appendix.

Instead, I’d like to talk about what this satiating power of protein means for Perfect Health Dieters.

Implications for Perfect Health Dieters

We have a fairly broad healthy protein range, 200 to 600 calories per day, which brackets the “normal” protein intake of 360 calories. What happens if you shift from 360 calories protein to either the low-protein or high-protein ends of the range?

IF YOU REDUCE PROTEIN: 

At low-protein intake, your appetite goes up and total calories go up. You gain a little weight, in the form of adipose mass. This causes leptin levels to increase. As we discussed in “How Does a Cell Avoid Obesity?”, higher leptin (a) lowers appetite and (b) increases thermogenesis, or destruction of fat as waste heat.

Adipose mass increases until the actions of leptin counterbalance the influence of protein leverage.

You reach equilibrium at a slightly higher fat mass and slightly higher leptin levels than on the “normal” protein intake.

IF YOU INCREASE PROTEIN:

At high protein intake, appetite goes down and total calories decrease. You start to lose adipose mass. This causes leptin levels to go down. This (a) increases appetite and (b) decreases thermogenesis, or heat generation.

Adipose mass decreases until a new equilibrium is reached. Equilibrium is reached at a slightly lower weight and slightly lower leptin than on the “normal” protein intake.

IN SHORT:

The main effect of changing the protein content of the diet is a modest change in body composition.

  • High-protein diets make you leaner and a little lighter.
  • Low-protein diets give you a slightly higher adipose reserve and make you slightly heavier.

The effect is probably small; probably just a few pounds either way. But if you’re looking for to win a bodybuilding competition and you have to become extremely lean and “cut,” you’d do well to adopt a high-protein diet.

It’s probably not a surprise, then, that people with the leanest bodies tend to be healthy but high-protein dieters. Here’s a picture of Anthony Colpo:

I think Anthony has a healthy body, but I don’t think you need to be this lean to be healthy. He would be equally healthy with a few more pounds of adipose tissue.

Conclusion

In the book we say that higher protein intake makes it easier to add muscle, and thus that it may be favored by athletes. Based on today’s post, we can adduce two other reasons to eat a high protein diet:

  1. A more chiseled body. If you want a lean, “cut” look, like Anthony Colpo, high protein will help.
  2. A controlled appetite. In a recent post, Don Matesz stated that he liked a high-protein diet because it helped him auto-regulate his calorie intake. If your goal is “effortless” (willpower-less) calorie restriction, then high protein may help – at least for a while.

However, there are reasons to restrict protein as well. Lower protein intake is likely to extend lifespan, and can increase immunity against intracellular bacteria and viruses, which are behind many late-life diseases.

Is it possible to achieve a lean, muscular body while still gaining the longevity and immunity advantages of low protein intake? And can one lose weight comfortably without assistance from a high-protein diet?  Those will be the topics of Thursday’s post.

References

[1] Astrup A. The satiating power of protein—a key to obesity prevention? Am J Clin Nutr. 2005 Jul;82(1):1-2. http://pmid.us/16002791.

[2] Simpson SJ, Raubenheimer D. Obesity: the protein leverage hypothesis. Obes Rev. 2005 May;6(2):133-42. http://pmid.us/15836464.

Appendix: The Protein Leverage Hypothesis as a Theory of Obesity

To the satiating power of protein, the protein leverage hypothesis adds two premises:

  1. That any increase in total calorie consumption leads to weight gain which induces insulin resistance in the liver, which in turn upregulates gluconeogenesis. Contrariwise, any decrease in calorie consumption reverses insulin resistance in the liver and downregulates gluconeogenesis.
  2. That the loss of protein associated with gluconeogenesis is treated by the brain’s appetite control centers exactly the same as a decreased intake of protein, and therefore that ongoing gluconeogenesis increases appetite immensely.

The theory of obesity is that once someone starts eating a low-protein diet, their appetite goes up. So they eat a larger amount of total calories, and gain weight. The weight gain causes them to become insulin resistant in the liver. Once that occurs gluconeogenesis is no longer inhibited by insulin, and the liver converts protein to glucose willy-nilly. The loss of protein stimulates appetite. But the person has to eat a lot of excess calories to get enough protein to replace the protein lost in gluconeogenesis. So weight goes up even more. There is a vicious spiral.

If these premises were correct, then:

  • Weight would be unstable. Weight would spiral out of control upward if people ate low-protein diets, and people would wither away once they started eating high-protein diets.
  • Low-carb diets would be extremely obesogenic. Every 1 calorie reduction in carb intake below the body’s daily needs of 600 calories would induce the eating of an extra 1 calorie of protein for purposes of gluconeoegenesis, and on the order of 4 extra calories of fat (by the leverage hypothesis: the P:F ratio stays constant). So each reduction of carb intake by 1 calorie leads to an extra ~5 P+F calories and an increase in total energy intake of 4 calories. Zero-carb diets would induce ravenous appetite, consumption of an extra 3,000 calories per day above the amount needed for weight stability, and obesity and metabolic syndrome would rapidly follow.

Neither is the case.

Why We Get Fat: Food Toxins

Posted by on January 20, 2011 88 comments

Erich asked about the link between omega-6 fats and obesity. It’s a good question and also a good way to introduce the first step of the Perfect Health Diet weight loss program:  removal of toxic foods from the diet.

Vegetable Oils With Fructose or Alcohol

These toxic foods are particularly dangerous in combination. We discuss this mix of toxins in the book (pp 56-59).

If you feed lab animals high doses of polyunsaturated fat (either omega-6 or omega-3 will do) along with high doses of either fructose or alcohol, then fatty liver disease develops along with metabolic syndrome. Metabolic syndrome is a major risk factor for obesity, and it’s not very difficult to induce obesity on these diets.

Both sugar and vegetable oils are individually risks for obesity:

  • Stephan did a nice post a few years back, “Vegetable Oil and Weight Gain,” discussing a couple of studies showing that both rats and humans get fatter the more polyunsaturated fat they eat.
  • Dr. Richard Johnson and colleagues did a review of the evidence for sugar (fructose) as a cause of obesity in the American Journal of Clinical Nutrition a few years ago. [1]

What the animal studies show us is that when fructose and vegetable oils are consumed together, they multiply each other’s obesity-inducing effects.

Here are a few pictures illustrating the correlation between polyunsaturated fat consumption, fructose consumption, and obesity.

Here is the Johnson et al chart showing historical fructose consumption in the UK and US [1]:

Here is Stephan’s chart showing historical polyunsaturated fat consumption in the US:

And here are obesity rates in the US:

Cereal Grains

It’s a common observation that the toxic grains, especially wheat, can produce a potbelly or “beer belly.” Rice doesn’t seem to do that.

There is epidemiological evidence for this effect. Here, for instance, is obesity prevalence by country from the World Health Organization Global Infobase:

Note the low obesity prevalence in the rice eating countries of China, India, Japan, Indonesia, and southeast Asia; and in sub-Saharan Africa, where a diversity of starch sources are eaten, including manioc/cassava, sorghum, millet, rice, maize, and wheat. The highest obesity prevalence is found in wheat-eating countries.

This correlation persists within countries. In the China Study, the correlation of wheat consumption with BMI was 56%, whereas the correlation of total calorie intake with BMI was only 13%. (Since total calorie intake is correlated with muscle mass, total calorie intake may be completely uncorrelated with fat mass. It’s not how much you eat, but how much wheat!)

Similar outcomes occur in mice. I can’t find any mouse studies comparing wheat to rice, but I did find one comparing wheat to rye [4]. Wheat was far more obesity-inducing than rye:

Body fat percentage was 20.2% in the wheat group, 13.7% in the rye group; fasting insulin was 126 pM in the wheat group, 90 pM in the rye group; and fasting cholesterol, triglycerides, and free fatty acids were higher in the wheat group.

In short:  wheat made mice fatter, more insulin resistant, and more dyslipidemic than rye.

Just for fun here’s a picture comparing fat tissue in the rye (left) versus wheat (right) fed mice:

I believe that rice would have done even better than rye, but I was unable to find a paper directly comparing rice vs wheat or rye.

Why We Get Fat

This brings me to a point of difference with Gary Taubes. Although glucose is toxic in high doses, the body has an extensive machinery for disposing of excess glucose. As we discussed in our last post, all tissues of the body participate in glucose disposal. Dietary glucose is not likely to do much damage unless the body’s glucose-disposal machinery has been damaged by other toxins first.

Obesity is caused not by carb calories per se, but by natural plant toxins. Plants, not carbs, make you fat!

It’s possible, by the way, that differing toxicities among grains could be responsible for epidemiological evidence favoring “whole grains” over “refined grains.” In America, products made with refined grains are usually 100% wheat; but products made with whole grains are often of mixed origin (“7 grain bread”). Since wheat is the most obesity-inducing grain, dilution of wheat content may be masking the toxicity of whole grains.

Conclusion

Certain toxic foods seem to be very effective at causing obesity:  vegetable oils, fructose, and wheat. Along with malnourishment (for instance, by choline deficiency) and infectious disease, food toxins are why we get fat.

The first step in any weight loss effort, therefore, ought to be removal of these toxic foods from the diet. Removing these toxins may not cure obesity; but without this step a cure is unlikely.

References

[1] Johnson RJ et al. Potential role of sugar (fructose) in the epidemic of hypertension, obesity and the metabolic syndrome, diabetes, kidney disease, and cardiovascular disease. Am J Clin Nutr. 2007 Oct;86(4):899-906. http://pmid.us/17921363.

[2] Andersson U et al. Metabolic effects of whole grain wheat and whole grain rye in the C57BL/6J mouse. Nutrition. 2010 Feb;26(2):230-9. http://pmid.us/19647415.