Grain Brain, Sugars, and Brain Health

 

James R Hamblin's review (This Is Your Brain on Gluten) in The Atlantic (where he is a senior editor) of David Perlmutter's Grain Brain: The Surprising Truth about Wheat, Carbs, and Sugar--Your Brain's Silent Killers has generated a lot of backlash against Perlmutter's claims in the book.

Perlmutter makes a few claims that are nearly opposite of what mainstream nutrition teaches us is true (as in the 1992 USDA Food Pyramid above):

1. Gluten is poison, and we should not eat any wheat (or rye, barley, and several other grains)
2. Sugars, especially fructose, are also poisons and we should seriously restrict their intake
3. LDL cholesterol is only a problem when it becomes oxidized (which occurs with carbohydrate consumption)
4. Cholesterol is good for us - there is no such thing as too much
5. If we adhere to these four points, we can prevent a LOT of neurodegenerative diseases

Perlmutter has introduced his own "inverse food pyramid" that resembles the one created by Dr. Mercola, although Perlmutter places an even greater emphasis on consuming fats (they should be 70% of our calories according to his model) than Mercola does:

 

There is also a brief video of Perlmutter outlining his inverse food pyramid:


Hamblin's review in The Atlantic was highly skeptical in tone and content - but while he tried to refute several of Perlmutter's central ideas, the research he sites supports the premise, although it is not nearly as conclusive as Perlmutter presents it.

I read the book with an eye for the most dangerous claim. What stuck out to me was Perlmutter’s case for cholesterol. He basically says that we can’t have too much.

“Nothing could be further from the truth than the myth that if we lower our cholesterol levels, we might have a chance of living longer and healthier lives,” Perlmutter writes . He recommends disowning the notion that LDL is bad cholesterol and HDL is good cholesterol; rather, both are generally good. LDL is only bad when it is oxidized, and it only becomes so in the presence of the sort of oxidative stress brought about by carbs and gluten. Avoid those, and cholesterol is innocuous.

Beyond that, Perlmutter says that cholesterol-lowering statin medicines like Lipitor, which are prescribed for a quarter of Americans over 40, should actually be vehemently avoided. Cholesterol is necessary for the brain in high levels, he says, and lowering it is contributing to dementia.

I took this to Katz, too.

“Is there a weight of evidence that says we can totally ignore both dietary cholesterol and LDL? Absolutely not,” he said. “You can legitimately say we’re starting to rethink some things, but ignoring LDL could absolutely result in heart attacks and strokes. Perlmutter is way ahead of any justifiable conclusion.”

The medical community’s understanding of the danger of cholesterol is changing. Many cardiologists are starting to think that independent of other considerations, the level of LDL in our blood may not be as important as it previously seemed. In November, the American Heart Association and the American College of Cardiology released new guidelines that redefined the use of statins. While they continue to recommend that people at high risk for heart disease and people with LDL levels above 189 take a statin, the long-standing goal of lowering one’s LDL level to 70 is no longer deemed worthwhile to monitor.

The reality about cholesterol is not quite as clear-cut as Perlmutter argues, but it is true that there is only about a 5-15% correlation between dietary intake of cholesterol and blood levels of cholesterol. From Wikipedia:

Most ingested cholesterol is esterified, and esterified cholesterol is poorly absorbed. The body also compensates for any absorption of additional cholesterol by reducing cholesterol synthesis.^[9] For these reasons, cholesterol intake in food has little, if any, effect on total body cholesterol content or concentrations of cholesterol in the blood.

The primary reason for this, as Perlmutter describes, is that the body would much prefer to use dietary cholesterol for the many cellular and hormonal processes based on its metabolism (most notably as an essential structural component of cell membranes and necessary to establish proper membrane permeability and fluidity, as well as it's role as the building block of sex hormones like testosterone and estrogen). Making cholesterol from sugars and saturated fats is an energy demanding process. Importantly, cholesterol is NOT really a fat - it is technically a sterol, a modified steroid.

LDL cholesterol is the evil cause of heart disease and a host of other diseases according to the medical mainstream. However, research from a few years back indicates that low cholesterol may actually cause more non-coronary deaths than high cholesterol. Moreover, as Perlmutter argues, statins that lower cholesterol compromise brain function because they don't only stop the liver from making cholesterol, they also stop the brain from doing so.

Yeon-Kyun Shin, a biophysics professor in the department of biochemistry, biophysics and molecular biology, says the results of his study show that drugs that inhibit the liver from making cholesterol may also keep the brain from making cholesterol, which is vital to efficient brain function.

"If you deprive cholesterol from the brain, then you directly affect the machinery that triggers the release of neurotransmitters," said Shin. "Neurotransmitters affect the data-processing and memory functions. In other words -- how smart you are and how well you remember things."

Another fallacy around cholesterol and health is that fat is the primary source of increased circulating LDL cholesterol. Fructose is a much larger issue - as soon as fructose is ingested it goes straight to the liver where it is converted into triglycerides to be stored as fat. Considering the enormous levels of high-fructose corn syrup consumed by the Western world, it's no wonder obesity is such a rampant problem.

The effects of different dietary sugars, with or without exogenously induced hyperinsulinemia, on rat plasma triglyceride kinetics have been studied. Glucose, sucrose, or fructose were supplied as 10% drinking solutions. The sugar-supplemented groups were each divided into subgroups, one receiving 6 U of insulin per day for 2 wk from intraperitoneally implanted minipumps and the other receiving none. The same degree of hyperglycemia and of endogenous hyperinsulinemia was seen in each sugar-supplemented group. Infusing exogenous insulin restored normoglycemia and produced more pronounced but equal hyperinsulinemia in each subgroup. In those rats that received no exogenous insulin, triglyceride production increased 18% in the sucrose-supplemented group and 20% in the fructose supplemented subgroups, but not at all in the glucose-supplemented subgroup. This 20% increase in triglyceride production in the fructose-supplemented subgroup was accompanied by a six times greater (120%) increase in triglyceride concentration. This suggested that dietary fructose not only increased triglyceride production, but also impaired triglyceride removal. Exogenously induced hyperinsulinemia further increased triglyceride production in those rats receiving dietary fructose, either as the monosaccharide or as sucrose, but not in those receiving only glucose. Thus, in the presence of fructose, but not glucose, insulin stimulates triglyceride production. As exogenous insulin returned the triglyceride concentrations to normal in the fructose-supplemented rats, it also appeared to overcome any fructose-associated impairment of triglyceride removal.

[Emphasis added.] While fructose is clearly the culprit in triglyceride levels, glucose is not so harmless as the above study might indicate. Perlmutter claims that glucose is very damaging to the brain, and there is research to support a correlation, although not yet a causative relationship:

Our results indicate that even in the absence of manifest type 2 diabetes mellitus or impaired glucose tolerance, chronically higher blood glucose levels exert a negative influence on cognition, possibly mediated by structural changes in learning-relevant brain areas. Therefore, stratgies aimed at lowering glucose levels even in the normal range may beneficially influence cognition in the older population, a hypothesis to be examined in future interventional trials.

So it appears that Perlmutter is not so far off after all. He is a little too absolute given the current evidence, but it's not likely that the millions of Americans who read his book are actually going to stop eating wheat and other grain products - Americans are simply not that concerned with the long-term consequences of immediate whims and desires.

Here is a longer talk by Perlmutter being interviewed for Underground Wellness:


Here are time notes:

5:06 -- The impact Dr. Perlmutter had on Dr. Oz.
9:10 -- Why you shouldn't let the government tell you what to eat.
14:42 -- LDL vs oxidized LDL -- know the difference!
17:10 -- 4 vital functions that require cholesterol in the brain.
20:20 -- Why cholesterol should be your BFF, not your worst enemy.
23:43 -- Is whole-grain wheat bread more toxic than a Snickers bar?
29:07 -- Your brain on gluten.
32:20 -- Heard of leaky gut? There's even leaky brain.
34:15 -- Do your kids a favor -- put them on a gluten-free diet.
36:15 -- Dr. Perlmutter's opinion on quinoa.
38:40 -- The antioxidant hoax. And why Sean was right about Protandim.
40:52 -- 5 foods that prevent oxidative stress.
42:00 -- Caller Q: Can gluten-free products still affect the brain?
44:26 -- Caller Q: Is brain fog the result of a gluten sensitivity?
46:47 -- Caller Q: How effective is liposomal glutathione?
49:10 -- Caller Q: If you're on a gluten-free diet, do you only eat protein and vegetables?
51:06 -- Caller Q: Are there other harmful elements in grains beyond gluten?
55:45 -- Caller Q: Is there a difference between the diet Dr. Perlmutter recommends and the paleo diet?
57:30 -- Caller Q: What is Dr. Perlmutter's opinion on the supplement KetoForce?
1:01:24 -- Caller Q: Can you fully recover from damage caused by gluten?
1:03:10 -- Why MS is a gut-related disease
1:09:41 -- Suffering from blood sugar issues? Here's a marker you should test for.
1:15:35 -- How to lower triglycerides.
1:16:33 -- Report your gluten-free success stories to Dr. Perlmutter!
1:17:56 -- The Grain Brain breakdown.

Dr. Robert Lustig - Fat Chance: Fructose 2.0

 

Dr. Robert Lustig is a professor in the UC San Francisco Division of Pediatric Endocrinology, and he has previously been featured on UCTV with his talk, Sugar: The Bitter Truth, of which this talk is an update. He argues that fructose (too much) and fiber (not enough) appear to be cornerstones of the obesity epidemic through their effects on insulin.



A little background from Wikipedia:

[Dr. Lustig] practices in the field of neuroendocrinology, with an emphasis on the regulation of energy balance by the central nervous system.[2] He also has a special interest in childhood obesity.[2]

Lustig came to public attention through his efforts to establish that fructose can have serious deleterious effects on human (especially children's) health if consumed in too large amounts.[3] On May 26, 2009, he delivered a lecture called "Sugar: The Bitter Truth" which was posted on YouTube the following July and "went viral" with some 3.47 million viewings (as of Apr 28, 2013).[3] In his lecture, Lustig calls fructose a "poison" and equates its metabolic effects with those of ethanol.

Lustig is the author of Fat Chance: Beating the Odds Against Sugar, Processed Food, Obesity, and Disease (2012).

Fat Chance: Fructose 2.0

Published on Oct 18, 2013

Dr. Robert Lustig, UCSF Division of Pediatric Endocrinology, updates his very popular video "Sugar: The Bitter Truth." He argues that sugar and processed foods are driving the obesity epidemic, which in turn affects our endocrine system. Series: "UCSF Osher Center for Integrative Medicine presents Mini Medical School for the Public" [10/2013]

(Visit: UCTV)

Dr. Robert Lustig: "Fat Chance: Beating The Odds Against Sugar, Processed Food, Obesity, and Disease"

Here are two recent articles/interviews with Dr. Robert Lustig about his new book, Fat Chance: Beating The Odds Against Sugar, Processed Food, Obesity, and Disease, the first is from The Diane Rehm Show and the other is from The Guardian (UK). Dr. Lustig argues that fructose (too much) and fiber (too little) are the cornerstones of the obesity and diabetes epidemics.

Robert H. Lustig, M.D has spent the past sixteen years treating childhood obesity and studying the effects of sugar on the central nervous system and metabolism. He is the Director of the UCSF Weight Assessment for Teen and Child Health Program and also a member of the Obesity Task Force of the Endocrine Society.

Here is some info on the book, via the publisher:

Robert Lustig’s 90-minute YouTube video “Sugar: The Bitter Truth”, has been viewed more than two million times. Now, in this much anticipated book, he documents the science and the politics that has led to the pandemic of chronic disease over the last 30 years. 

In the late 1970s when the government mandated we get the fat out of our food, the food industry responded by pouring more sugar in. The result has been a perfect storm, disastrously altering our biochemistry and driving our eating habits out of our control. 

To help us lose weight and recover our health, Lustig presents personal strategies to readjust the key hormones that regulate hunger, reward, and stress; and societal strategies to improve the health of the next generation. Compelling, controversial, and completely based in science, Fat Chance debunks the widely held notion to prove “a calorie is NOT a calorie”, and takes that science to its logical conclusion to improve health worldwide.

Other reviews/interviews can be found at KQED, Talk of the Nation, Oprah, and The Chicago Tribune, among many others.

Here is the episode from Diane Rehm:

Dr. Robert Lustig: "Fat Chance: Beating The Odds Against Sugar, Processed Food, Obesity, and Disease"

LISTEN
TRANSCRIPT
ORDER A CD

Monday, January 7, 2013

Recently published research suggests that obese people have a lower risk of death compared to people with normal weight. But this is not news to pediatric endocrinologist, Robert Lustig. He says fat doesn’t matter. What does matter, he argues, is metabolic function. For the past 16 years, he’s been treating childhood obesity and studying the effects of sugar on the central nervous system. In a new book he details the science and politics behind the dramatic increase in our consumption of sugar and explains why this shift is so detrimental to our health. Please join us to talk with Dr. Robert Lustig about obesity and disease.

Guests: Dr. Robert Lustig, Director of University of California, San Fransisco Weight Assessment for Teen and Child Health Program.

Related Links
Sugar: The Bitter Truth video (or watch it below)

Related Items

Fat Chance: Beating the Odds Against Sugar, Processed Food, Obesity, and Disease

"Sugar: The Bitter Truth" - Dr. Robert Lustig breaks down what sugar does to the body.

Read An Excerpt

Here is the review from The Guardian:

Fat Chance: The Bitter Truth About Sugar by Robert Lustig – review

Why eating sweet food is bad for you, but might not be your fault

Steven Poole
The Guardian, Friday 25 January 2013

A worker at a Turkish sugar refinery is dwarfed by mountains of beet. Photograph: Umit Bektas/Reuters

Here's a mini-quiz for foodists who pride themselves on their knowledge of obscure consumables: what are diastatic malt, dextran, ethyl maltol, panocha and sorghum syrup? They are all names used on food labels for added sugar. Robert Lustig, an endocrinologist who works on childhood obesity, is angry with the food industry and the capturing of western governments by its lobbyists. Added sugar is all around us, disguised under deliberately unfamiliar names, and its sweet molecule – fructose – is, according to Lustig, the prime cause of our ballooning "obesity pandemic".

Lustig explains the biochemistry of metabolism, and the vicious cycle of obesity, with patient clarity and some alarmingly vivid imagery. (You know the way sugar helps to brown meat while cooking? It's browning your insides the same way.) He is sceptical about one-shot solutions (miracle diet pills, antioxidants), since there is a complex interdependence between the actions of hormones and food intake. For example: there is fructose in fruit, so why isn't eating fruit bad? Because the fibre in fruit counteracts the noxious effects of the sugar, which is why it's better to eat your fruit than to drink it. (A glass of orange juice contains more sugar than the equivalent volume of Coke.) The bitter pill of Lustig's philosophy is sweetened by an agreeably cute humour: "Naturally occurring fructose comes from sugarcane, fruits, some vegetables, and honey. The first three have way more fibre than fructose, and the last is protected by bees."

There is no shortage of fad food books blaming one or other "toxin" for all our fleshly dolours. Yet to dismiss every such tract as populist scaremongering would be just as irrational as to believe them all. (The "experts" – whom it is fashionable in some quarters always to dismiss wholesale as a compromised class – did not, after all, turn out to be wrong about the harmful effects of cigarettes.) Recent reports elsewhere, indeed, indicate that there is a growing consensus behind the idea that the fructose factor helps to explain what otherwise looks like a puzzle: why do different diets – Atkins, the Paleo diet, the traditional Japanese or Mediterranean diets – all have notable health benefits? Because, or so this thinking runs, they are all low-sugar and high-fibre regimes.

Fat Chance is a persuasively indignant public-policy manifesto, but it's also a self-help book; curiously, each strain flatly contradicts the other. The crux is whether people can actually change their behaviour. Of course they can, you might retort, citing friends who have successfully slimmed; but Lustig spends most of the book denying that this is even possible, the better to justify government regulation. (He suggests agricultural subsidies for green vegetables instead of for corn and soy, and taxing foods that have added sugar. This latter would be a regressive tax, he admits, but the benefits would also accrue mostly to those on low incomes.)

Lustig denies personal autonomy for laudably humane reasons – because he wants to deconstruct the prejudice that obese people have merely given in to "gluttony and sloth". But his insistence on the complete irrelevance of "personal responsibility" leads him to rely on some ropey metaphysics and oversimplified science. "Biochemistry and hormones drive our behaviour," he writes reductively, assuring us that we are merely slaves to the antic nanoreactions of our neurobiology. And because obesity changes our hormonal balance, "weight loss is next to impossible".

Apparently, then, we can't choose what to do. "Most of the world views the word behaviour as meaning the actions we choose to do or not through 'free will,'" he writes. "However, the dictionary definition of behaviour is: 'a stereotyped motor response to a physiological stimulus.'" Unfortunately, Lustig does not provide a footnote to indicate which dictionary he was using. I checked the OED, the New Oxford American Dictionary, and Merriam-Webster, and none gave his definition of "behaviour" as primary. Lustig's description is a more specialised one, recalling the tradition of "behaviourism" in psychology. An animal's actions in this sense could be "conditioned", as in BF Skinner's famousSkinner box: a rat in the box learned to push one button for food and avoid the button that generated electric shocks. There's probably a bracing argument to be made that modern humans all live in a giant Skinner box, but Lustig doesn't come out and make it.

On the other hand, if Lustig's anti-free-will view is correct, it is hard to see the point of his urging the reader, in the book's self-help chapters, to alter his or her own buying and eating habits. Even so, he provides a six-page shopping list of low-fructose and high‑fibre foods that one can find in any supermarket; and offers advice on how to behave in a restaurant. (Don't be in a fast-food joint in the first place; don't have bread with the meal; don't order dessert.) So personal change is possible?

This is not to say that Lustig's advice isn't good. In fact, you can tell it is good because it is so close to what everyone already knows, despite his eagerness to sell the novelty of his version and dismiss the familiar mantra of "eat less and exercise more" as a "myth". So what is his answer? Er, eat less sugar, eat more fibre, and exercise more. Or, if you want it further reduced: avoid "processed" rubbish and just "eat real food". I worried for a moment that much of my own diet would, on Lustig's stringent criteria, turn out to have been unreal food: merely colourful hallucinations of elaborate victuals, simulated scoffing. But then I couldn't help myself, could I?

• Steven Poole's You Aren't What You Eat is published by Union Books.

High Fructose Intake Linked to Poor Liver Health

Unlike glucose (the simplest sugar, and the foundation of carbohydrate energy use in the body), which can be metabolized and used for energy by cells throughout the body, fructose (fruit sugar) must be metabolized through a rather complex process in the liver, where some of it becomes glucose eventually, and a substantial portion is bound in triglycerides, destined to become very-low-density lipoproteins (VLDL) or be stored as fat (or to clog arteries as VLDL cholesterol).

A new study shows that this process, fructolysis, increases uric acid levels in the liver and decreases  ATP levels (the energy that powers cells) - this was with obese and diabetic subjects, but there is ample evidence that this is not confined only to this population.

For the present study, 244 obese and diabetic adults from the Look AHEAD Study were evaluated, with dietary fructose consumption estimated by the food frequency questionnaire. Liver ATP and uric acid levels were measured in 105 patients who participated in the Look AHEAD Fatty Liver Ancillary Study. Researchers assessed the change in liver ATP content using an IV fructose challenge in 25 subjects, comparing patients with low fructose consumption (less than 15 grams per day) to those with high fructose consumption (greater than 15 grams per day).

The team found that participants with a high intake of dietary fructose had lower liver ATP levels at baseline and a greater change in ATP content following the fructose challenge than those who consumed a lower amount of fructose. Patients with high uric acid levels (5.5 mg/dL or more) displayed lower ATP stores in response to fructose.

Dr. Abdelmalek concludes, “High fructose consumption and elevated levels of uric acid are associated with more severe depletion of liver ATP. Our findings suggest that increased dietary fructose intake may impair liver “energy balance.” Further research to define the clinical implications of these findings on metabolism and NAFLD is necessary.” The authors highlight the importance of public awareness of the risks associated with a diet high in fructose.

The study citation, as given in the press release:
“Higher Dietary Fructose Is Associated with Impaired Hepatic ATP Homeostasis in Obese Individuals with Type 2 Diabetes.” Manal F. Abdelmalek, Mariana Lazo, Alena Horska, Susanne Bonekamp, Edward W. Lipkin, Ashok Balasubramanyam, John P. Bantle, Richard J. Johnson, Anna Mae Diehl, Jeanne M. Clark, and the Fatty Liver Subgroup of the Look AHEAD Research Group. Hepatology; (DOI: 10.1002/hep.25741); Print Issue Date: September, 2012. URL: http://onlinelibrary.wiley.com/doi/10.1002/hep.25741/abstract

Here is some additional information on fructose metabolism from Wikipedia:

Metabolism

In a 2012 meta-analysis of controlled feeding clinical trials, fructose was not an independent factor for weight gain. Fructose consumption did cause weight gain in a diet with excessive calories, which could be due to the extra calories rather than fructose per se.^[40]

Excess fructose consumption has been hypothesized to be a cause of insulin resistance, obesity,^[41] elevated LDL cholesterol and triglycerides, leading to metabolic syndrome.^[42] In preliminary research, fructose consumption was correlated with obesity.^[43][44] A study in mice showed that a high fructose intake may increase adiposity.^[45]

Although all simple sugars have nearly identical chemical formulae, each has distinct chemical properties. This can be illustrated with pure fructose. A journal article reports that, "...fructose given alone increased the blood glucose almost as much as a similar amount of glucose (78% of the glucose-alone area)".^{[46][47][48][48][49]}

In Wistar fatty rats, a laboratory model of diabetes, 10% fructose feeding as opposed to 10% glucose feeding was found to increase blood triglyceride levels by 86%, whereas the same amount of glucose had no effect on triglycerides.^[50] Neither glucose nor fructose influenced insulin or blood sugar in this model. The authors concluded "These results show that in genetically obese, diabetic rats feeding fructose and glucose is associated with an increase in hepatic lipogenic enzyme activities and triglyceride production, and suggest that fructose stimulates triglyceride production but impairs triglyceride removal, whereas glucose stimulates both of them.^[50]

Another study in humans concluded that fructose and sucrose are metabolized similarly,^[51] whereas a different analysis "produced significantly higher fasting plasma triglyceride values than did the glucose diet in men" and "...if plasma triacylglycerols are a risk factor for cardiovascular disease, then diets high in fructose may be undesirable".^[52]

Fructose is a reducing sugar, as are all monosaccharides. The spontaneous chemical reaction of simple sugar molecules binding to proteins is known as glycation. Showing potential cause of skin and bone damage in a rat model of diabetes, investigators suggested "that long-term fructose consumption negatively affects the aging process."^[53] Another study using human proteins showed that the glycation caused by fructose appears to be equivalent to glucose and so does not seem to be a better answer for diabetes for this reason alone, save for the smaller quantities required to achieve equivalent sweetness in some foods. It also found evidence for glycation of human lens proteins caused by fructose.^[54]

The people most at risk of increased triglycerides and fat storage from eating fructose are those who are consuming more calories than they need. Consumption of high-fructose corn syrup is also a huge risk factor for anyone, healthy or overweight.

If you eat fruits, and you should, be sure your daily calorie intake is in check and that you are exercising regularly. Then, try to choose fruits lower in sugar, such as apples, berries, melons, and so on, that also offer good nutrient and antioxidant benefits.