Why you can all stop saying meat eating fueled evolution of larger brains right now

Hadza returning from hunt in Tanzania. Credit Andy Lederer.

In William Shakespeare’s comedy Twelfth Night, Sir Andrew, who was worried that a joke may have been made at his expense, reasons out loud that maybe his diet had something to do with his lack of intelligence, saying, “But I am a great eater of beef, and I believe that does harm to my wit” (Act I, Scene III). Dialogue like that was how Shakespeare famously poked fun at what he considered “foolery” in his time; it was a common belief of the Elizabethan Age that eating too much meat made you a meat-head. Now, it appears the tables have turned. Vegetarians are getting a taste of similar medicine from comedians of our time.

On November 15th’s episode of The Colbert Report, Stephen Colbert interviewed one of the world’s foremost paleoanthropologists, Chris Stringer of the Natural History Museum, about his newly published book. During their conversation, Stringer sums up nicely why meat eating may have been the primary force that drove evolution of a brain-gut tradeoff, where a shrinking gut allowed for more energy input into the brain. Here is Stringer’s explanation at about minute 18:30 in the episode:

Chris Stringer: “There’s a thing called ‘expensive tissue hypothesis’. And this says we evolved our large brains by changing our diets. Our ancestors had great big guts because they were vegetarian. They never had enough spare energy because their guts were using 20 percent of their energy; they never had enough spare energy to evolve a large brain. When we started eating meat, a much more concentrated sort of food, it freed up energy and we could start to run a bigger brain.”

Stephen Colbert: “That’s why vegetarianism seems so stupid to me.”

There’s little use challenging the evidence that meat, whether eaten raw or cooked, was “brain food” for our ancestors. The fossil record shows a clear correlation between the appearance of hominin meat eating some two million years ago — as evidenced by stone tools, cutmarked bones, and changes in hominin teeth structure — and the drastic increase in cranial size that continued until the agricultural revolution. Studies in genetics and in primatology add more support that meat helped enable our ancestors to attain the nutrients required for the development of all our extra neurons. In my last post, for example, I discuss Greg Wray’s research on how changes in differences of fat metabolism and neuronal signaling that may have developed as a result of more meat in the diet and probably helped produce our fatter brains.

However, while meat eating may have played a role, the arguments espoused often by writers, “paleo” and Atkins enthusiasts, and meat-lovers of all kinds are often flawed from a nutritional standpoint. The problem is, it just doesn’t make a lot of sense that meat eating could have fueled evolution of our larger brains. It’s more likely that carbs did.

Neurons run on glucose, not meat

Neurons, which use twice the energy as any other cell type in the body, run almost exclusively on glucose. They don’t run on protein and fat.* Moreover, because neurons aren’t able to store glucose as glycogen as other cells in the body do, they must receive glucose in constant supply. That’s glucose that must be received from the bloodstream 24 hours a day, seven days a week, even while you’re asleep. That’s glucose for some 86 billion neurons, more than any other primate; by comparison, gorillas contain about 33 billion and chimpanzees only 28 billion neurons. That’s glucose in amounts that could not possibly be supplied by any abundance of meat eating.

A human brain is ~3x larger than a chimp’s.

To get an expert’s standpoint on the topic, I wrote to Peter Ungar, distinguished professor and chair of anthropology at University of Arkansas, who was recently named a fellow of the American Association for the Advancement of Science, what his take was on the role of meat eating versus carbs in human brain evolution. He wrote back,

Even the staunchest meat advocates recognize that protein and fat cannot power the brain – and we lose much of our gluconeogenesis capabilities at weaning. The argument is that meat eating provided the calories needed to power other parts of the body, freeing available carbohydrates to focus on the brain… Even in that case, it’s carbs, not meat that powers the brain (even though meat facilitates the process).

So, let me repeat in my own way: Why was meat important for evolution of larger brains? Although meat does provide some valuable micronutrients and essential fats, there may not be anything incredibly special about meat nutritionally except that it freed up carbohydrate calories for feeding brains that were roughly three times larger than chimps without the use of gluconeogenesis (synthesis of glucose).

According to Wray’s evidence from regulatory genes, humans also developed double the glucose transporters in the brain in comparison to chimps. Chimps, on the other hand, have double the glucose transporters in their muscles. That translates to about four times more glucose going to our brains versus our muscles in comparison to chimps. When I asked Ungar what he thought regarding the role of other types foods (e.g. tubers), as well as preparation techniques (e.g. cooking) in also freeing carbs for the brain, he responded,

I believe the hominin lifestyle is more about a broadened niche than meat per se… Lots of people live in lots of places because they can find something to nourish themselves in whatever environment they find themselves in. Western Australian aboriginals did quite well without lots of meat. 

On Wray’s research, Ungar also added,

I’m not an expert on fueling the brain, but it makes sense to me that we’re more efficient at getting glucose across (we need it). One could argue that this allows LESS carb intake for a given brain size… Since our brains are roughly 4x the size of Chimps, does that mean we need about the same number of carbs to power them? 

As for evidence of increased starchy food intake – I think the amylase gene copies didn’t take off until relatively recently. Still, evidence of a broadened subsistence base in Homo could certainly have included starchy foods, meat, or anything else they could get their hands on. 

I’m pretty conservative in terms of single-cause, magic bullet explanations without solid evidence from the fossils themselves… Maybe it’s my time chasing broad-diet primates in the rainforest, but I’m hesitant to invoke one food type to explain brain expansion.

Lastly, he wrote,

…the problem now is coming up with ways of testing those hypotheses (meat, cooking, flexibility, fish, etc). In the end, I woudn’t be surprised if there were no magic bullet…  but after all the new and exciting findings coming from isotopes, microwear, etc. not much would surprise me re: the evolution of human diet.

So there you have it — it’s more appropriate to say that a “broadened niche” is what helped fuel evolution of larger brains. Meat provided micronutrients, but more of it more often probably did nothing more than provide more calories so that we could use carbs to fuel our brains. It’s certainly possible that other foods like cooking, shore-based foods, and other foods could’ve played the same role, too.

Cooking Was More Important Than Meat for Brains

In a recent live chat with science writer Ann Gibbons over at ScienceLive, biological anthropologist Richard Wrangham at Harvard and comparative neuroanatomist Suzana Herculano-Houzel had a few interesting things to say on this topic while discussing their recent study published in Proceedings of the National Academy of Sciences. Their study showed that humans would have to spend more than nine hours a day eating raw foods to feed hungry brains (at 2,000 kcal a day) despite whether raw meat was included or not.

In the chat, Wrangham said, as he’s argued in his book,

Cooking increases the net energy gained from food from 2 main routes. (1) It increases digestibility (the proportion of food that gets digested and absorbed). For instance cooking is estimated to increase the digestibility of starch in grains by around 30%. It also increases the digestibility of meat, by denaturing the protein. (2) It reduces the physiological costs of digesting our food – because cooking softens food, so it is easier to digest.

A commenter, Fred, questioned the role of meat eating versus cooking in leading to larger brains, to which Wrangham responded,

The meat vs. veg question is totally unresolved! Recent hunter-gatherers ate least meat near the equator, about 35% of diet, rising to ~100% near the poles. But recent hunter-gatherers are not necessarily good models for our ancestors. They have technology (bows and arrows, and poisons) that made hunting easier; but there again, there may have been more animals in the past. Also, the truly great places for hunter-gatherers to live in may have been those where farmers took over in masses, such as the Nile delta, with terrific plant supplies. So the ‘paleo-diet’ idea that our ancestors were all heavy meat-eaters doesn’t acknowledge the likely large variation in % meat / % plant. Anyway, nowadays vegetarians have about the same body mass index as meat-eaters. So meat doesn’t seem to do much to affect energy gain. (But raw-dieters, whether vegetarian or meat-eaters, are much thinner on average than cookivores, whether vegetarian or meat-eaters.) Bottom line: meat is less important than cooking when it comes to energy gain.

Is Wrangham suggesting redemption for raw dieting and vegetarianism as a healthy dietary approach in a modern world? Some people might think so. Although, as a nutritionist, I wouldn’t recommend them a raw or vegetarian diet. After all, animal protein is valuable for maintaining or building muscle because of its higher quality amino acid profile; specific animal fats (DHA and EPA) are valuable for cardiovascular and brain health; and animal foods generally do provide necessary micronutrients such as zinc that are important for brain health.

Yet, the point here is there was probably “no magic bullet” that led to evolution of human brains and that meat is not necessarily a brain food. Whatever the combination of factors — cooking, broadened niche, even food sharing — that led to larger brains, carbs are what really fuel your neurons, and that’s not to say you should overconsume carbs either; most of us already do too much of that. So, there’s no sense in using evolution of larger brains as an argument for gorging on steak. Too much beef (and too little glucose), as The Bard would’ve believed, really might do “harm to your wit.”

Update: I’m thrilled to share that this blog post was blogged about by Barbara J. King of NPR over at 13.7 — check it out here. Enjoy!

*12-7 note: Many of you have pointed out my statement “They don’t run on protein and fat” is not entirely accurate. Amino acids can be used to synthesize glucose, although this is a metabolically costly process in terms of ATP. As Ungar said, gluconeogenesis is limited in humans. Also, it is possible for the brain to use products of fat catabolism called ketones as fuel (to spare muscle amino acids; in fact, muscle will use ketones first); however, ketones are only use in the brain in periods of prolonged starvation (or on a diet extremely low in calories with little to no carbohydrates) and may lead to adverse health consequences. 

Holding on to brain function through nutrition

By the year 2050, the number of people in the world over 80 years old will reach 370 million. About 50 percent of adults currently 85 and older have Alzheimer’s disease. The statistics are sobering and warn of a growing and serious epidemic. A high prevalence of Alzheimer’s disease, which is a debilitating and costly disease, can severely impact the population.

With this perspective, the American Society for Nutrition hosted a symposium on the nutritional prevention of cognitive decline on Wednesday at Experimental Biology in San Diego. At the event, speakers presented a comprehensive overview of epidemiological, animal, and clinical trials regarding the role of B vitamins, omega-3s, vitamin D, and caffeinated beverages such as coffee and tea in the prevention and treatment of cognitive impairment.

Martha Morris, Ph.D., an epidemiologist at Tufts University, discussed the relationship of folic acid, B12, and homocysteine to age-related cognitive decline, dementia, and Alzheimer’s disease. In summary, she said, the evidence suggests that sufficient B12 intake could protect against cognitive decline related to elevated levels of homocysteine. However, once B12 status was replete, there was no further protection.

The next speaker to follow was Lenore Arab, Ph.D., nutritional epidemiologist at University of California, Los Angeles, who presented on the effects of caffeinated beverages coffee and tea. The popular drinks, of which many in attendance wished for during the early morning talk, showed promise in helping to slow cognitive decline according to evidence from observational, animal, and clinical data.

Tommy Cederholm, M.D., Ph.D., of Uppsala Universitet, Sweden, discussed the large amount of epidemiological studies and human clinical trials exploring the role of omega-3s. The data suggest plenty of biological mechanisms such as reducing inflammation and protection against amyloid-beta protein deposits.

“Fish is good for your brain,” Dr. Cederholm said, noting that intake may assist in early stages of cognitive impairment. However, he added, intake did not appear to assist in patients who already had Alzheimer’s disease.

Lastly, Joshua Miller, Ph.D., a professor of pathology of University of California, Davis, discussed new research findings that vitamin D played a major role in the brain development and function. The epidemiological and animal studies suggest a positive effect in the prevention or treatment of cognitive impairment, he said, but randomized controlled trials in humans were lacking. Unlike other micronutrients, he added, vitamin D has a complexity because of seasonal variation, which suggests it’s important to measure both in summer and in winter when performing studies.

Can carotenoids in the brain protect against Alzheimer’s?

Carotenoids are thought to protect against Alzheimer’s disease because of their antioxidant properties and their accumulation in the brain. However, a new study from Tufts University is putting the theory into question.

More than a century has passed since the German physician Dr. Alois Alzheimer first presented evidence on the case of Auguste Deter, who at only 51 suffered from severe memory loss and other psychological changes. At autopsy, Dr. Alzheimer found his patient had severe shrinkage and abnormal deposits of the nerve cells.

“That was in 1906,” said nutritionist Annie Roe, a USDA researcher at Tufts University, who presented her laboratory’s findings on April 21 at Experimental Biology 2012 in San Diego. “There’s still disparity among scientists as to the etiology of this rapidly growing disease as we now know as Alzheimer’s disease.”

Currently, in the United States there are 5.3 million people with Alzheimer’s disease. Unless new methods of intervention are available, however, the number is expected to reach 16 million by 2050. While the cause of the disease is not known, the deposits that Dr. Alzheimer first noted are now known to be amyloid-beta peptide deposits.

These deposits, or plaques, are a “hallmark diagnostic feature” of Alzheimer’s disease. Within the same region amyloid-beta plaques are found, increased concentrations of oxidized proteins, lipids DNA are also observed. It’s not yet clear whether or not that these products of oxidative stress caused the amyloid-beta plaque build-up or vice versa.

However, Roe said, it is clear that oxidative damage promotes neurotoxicity and is involved in cognitive impairment. Epidemiological studies have found that a higher dietary intake of carotenoids from fruits and vegetables are associated with reduced risk of age-related chronic diseases including Alzheimer’s disease. Other studies measuring the concentration of carotenoids in plasma have found an inverse relationship with chronic diseases.

Fruits and vegetables are the major sources of carotenoids in the diet, the most common of which are beta-carotene and beta-cryptoxanthin—two provitamin-A carotenoids. There is also lycopene, lutein, and zeaxanthin, which have no vitamin A activity. There are several biological mechanisms being explored for carotenoids’ potential protection to the brain.

However, Roe explained that her laboratory research focuses on the role of antioxidants and their relationship to Alzheimer’s disease, clinically determined by increased cognitive impairment. Since Alzheimer’s affects brain tissue, the researchers’ study purpose was to determine the concentration and magnitude of lipid peroxidation in brains diagnosed with Alzheimer’s disease compared with age-matched controls.

The Tufts laboratory received brain tissue samples from the National Institute for Child Health and Human Development (NICHD) Brain and Tissue Bank for Developmental Disorders. The samples were obtained from 15 individuals with Alzheimer’s disease and half with no known dementia. The samples were from subjects in their late 70s or early 80s, most of whom were Caucasians. The samples were of four different brain regions: occipital cortex, frontal cortex, hippocampus, and auditory cortex. To assess lipid peroxidation, the researchers extracted malondialdehyde (MDA)—a marker of oxidative damage—through HPLC.

When looking at relative distribution of major carotenoids between Alzheimer’s disease and controls, the study found the provitamin A carotenoids contributed to a significantly higher percentage of total carotenoids in the Alzheimer’s brains compared to the controls. Non-provitamin-A carotenoids contributed to higher concentration in control brains compared to Alzheimer’s disease brains, but there was no statistically significant difference.

In addition, Roe said, the absolute concentrations of provitamin-A carotenoids were higher in Alzheimer’s diseased samples versus control samples. There was no difference in absolute concentrations of lutein, zeaxanthin, or lycopene. There was also no significant difference between malondialdehyde concentrations and carotenoid concentrations.

Consistent with findings of increased pro-vitamin A carotenoids, retinol (vitamin A) concentration was significantly greater in the Alzheimer’s disease brains. However, when the study looked at malondialdehyde concentrations, there was not a significant difference between the two groups.

The findings “were interesting but unexpected,” Roe said, adding that when she looked at each region separately, she saw the same pattern in the hippocampus, a region that is highly vulnerable to the disease.

Since prior research has shown both in cell culture and in clinical studies that vitamin A can have a positive effect on beta-amyloid aggregation, it is possible that caregivers or physicians confounded results. For example, they may have encouraged their patients after diagnosis to consume more fruits and vegetables. It may be that carotenoids are beneficial to the brain, but simply not after the disease has set in. Roe suggests future studies should include dietary intake assessments and target people with earlier stages of dementia.

“This is just a snapshot view of a small group of people at the end of life, so we can’t infer any type of causation and certainly should not interpret the results to mean that vitamin A is bad for the brain,” Roe said.

The study’s results contradicted that of previous research, also presented at the conference by Neal Craft of Craft Technologies, which found an age-related decline of carotenoids in elderly brains that suggested that diminishing levels may be associated with Alzheimer’s disease.

Can we get any smarter? (A conversation with my boy about neuroscience)

A PET image showing energy consumption in the hungry brain. Credit: Wiki

“Can we get any smarter?” That is the question that piqued the interest of a 14-year-old boy yesterday when he saw it on the cover of the July issue of Scientific American. 

What came next was a reading of Douglas Fox’s fascinating “The Limits of Intelligence,” some heavy thought in a young teenager’s head, and a surprised father who rarely has a conversation with his son about neuroscience.

Plus, that same father is rarely met when he comes home from working all day to a welcome like this, “Hi dad. Do you want to go see a cool movie?”

The movie my boy wanted to see (with me!) was Limitless, a science fiction flick he’d seen before about a man who takes a drug that unlocks his ability to use the “other 80 percent of his brain.” We went to see it and, as my son pointed out after the movie, all of what was portrayed was just impossible.

Why? I asked. And that’s when my boy started telling me that any drug taken wouldn’t work because “we cannot get much smarter.” That is, without either:

• “enlarging are brains” to contain more neurons
• adding more connections between the neurons,
• increasing speed of which neurons signal each other — the latter of which my boy said would be hardly an improvement because “it would exhaust our energy.” 

With my mind totally blown with these sensible arguments, I asked, “How on Earth do you know all this, boy?”

“I was reading your magazine, Dad.”

*Awww… proud dad feelings* Anyway, I decided to read Fox’s article and was delighted to find all of the arguments my son was giving in it.

Plus, I found this gem in a paragraph quoting Mark Changizi (@markchangizi), a theoretical neurobiologist, on why bigger brains (as in elephants) and their specializations (through compartmentalizations of functions) doesn’t always equate to greater intelligence:

As you go from a mouse brain to a cow brain with 100 times as many neurons, it is impossible for neurons to expand quickly enough to stay just as well connected. Brains solve this problem by segregating like-functioned neurons into highly interconnected modules with far fewer long-distance connections between modules. The specialization between right and left hemispheres solves a similar problem; it reduces the amount of information that must flow between the hemispheres, which minimizes the number of long, interhemispheric axons that the brain needs to maintain. “All of these seemingly complex things about bigger brains are just the backbends that the brain has to do to satisfy the connectivity problem” as it gets larger, Changizi argues. “It doesn’t tell us that the brain is smarter.”

We like to think that our brains are pretty amazing, which they are. But, in short, Fox’s entire article with Chiangizi’s quote touches on a point we may not like to think about: our brain’s evolved limits.

And it was this message that my son came away with after reading the article, phasing out any dream he might have had of altering his brain for supreme intelligence and power after his first viewing of the sci-fi flick.

Being the father I am, my advice to my son was this:

“You’re right, you can’t really do much with what we got despite whatever drugs people might say do wonders. Maybe, maybe, one day humankind will be able to create tiny microchips or something to implant in our brains that will expand our minds. But, what then? Once our brains possess the capacity to do all that is Google, will we then be happy? Probably not.”

The fact is that our brains, despite all their glory, remain hard-wired with another evolved limitation that intelligence can’t help, I argued. It’s our need to seek out survival, food and health, shelter, and passing on of our genes.

Fox’s fascinating article about intelligence aside, I told my boy that perhaps it’s also time to look beyond what is intelligence, to what drives humankind’s sense of purpose.

Have humans reached the limits of how complex our brain can be? Perhaps. But we know that within these limits, humans appear to have unlimited capacity of expression of creativity, be it through writing, music, or art.

When I first heard Joseph Campbell say, “Follow your bliss,” I took that to mean that we can be accepting of what genetic predispositions our ancestors gave us, whether it be smarts, physical attractiveness, or an athletic body, and work with it toward something great, within or beyond our means.

The secret to life, if there be any, may be to just enjoy and develop our own talents to bring us all a bit of fun while we’re all still around here.

Deep-brain stimulation for depression

On Sunday morning at New Horizons in Science at Yale — after some coffee for brain stimulation — we were treated to our first science talk of the day: on deep-brain stimulation as a treatment for severe depression.

Emory University professor of psychiatry and neurology Helen Mayberg, MD, showed us several brain scans she uses to study moods and neural networks. She can tell from these neural images whether you’re glad, mad or sad.

Then, she targets areas of the brain with what she describes as an “implantation of a very, small wire… with electrodes on the end.” The electrodes are guided to wherever she wants it in the brain and an IPG is implanted in the chest.

Dr. Mayberg worried about the safety of acute stimulation of areas of the brain. What happens if you stimulate the hypothalamus and it causes a drop in blood pressure? But she couldn’t rely on surgeons as “gatekeepers,” so she performed intra-operative safety testing.

During the testing, patients self-reported spontaneous feelings such as “intense calm” or resolution of pain and dread — interoceptive release. These reports happened patient after patient, says Dr. Mayberg, so she knew something was going on. The feelings were followed by interest, energy — exteroceptive awareness.

Dr. Mayberg’s first study was published in 2005, then she expanded and published again in 2008 (in Biol Psych). The studies showed deep-brain stimulation was effective in treatment-resistant depression. “The [patients] not only got better, they stayed better,” she says.

She then gave us some preliminary results of an Emory study of active treatment for six months with a two-year follow-up on bipolar and unipolar patients. The results so far look very, very promising. “This is an anti-depressant treatment, not a mood stabilizer,” says Dr. Mayberg. “No one remains in pre-treatment state, everyone is on road to recovery.”

She says now we know not just where to stimulate in the brain, but what fibers must be impacted for the treatment — a treatment that can take patients with “gnawing pain” or feelings of “being in a room with 10 screaming children” to a place of a finding serious relief.

So, what’s next? Dr. Mayberg says the treatment needs to go through a series of placebo-controlled trials to establish safety and to confirm initial results.

Even more exciting, however, is that with neural images it may be possible to soon predict and even prevent depression. “This is teaching us an amazing amount about depression,” Dr. Mayberg says. The more we learn, the greater the understanding of what goes wrong in neural networks that leads to development of severe depressive disorders.

She’s careful to point out that a stimulator is not the only thing you need to come out of a depressive state and it’s not a device that will ever guarantee that people can forever say goodbye to “bad days.”

But along with continual therapy over time, from a patient’s perspective, the treatment can mean the difference between feeling like you are at the bottom of the Grand Canyon without any chance of hiking out and the feeling that you have when you have a pathway toward the top.

Dietary Interventions for Prevention and Reversal of Brain Aging

As part of Symposium II at American College of Nutrition conference in New York City, we are now enjoying a talk by PATH Medical director Eric Braverman, M.D., FACN.

Braverman starts out talking about how “the brain is the most important organ” and you can have “too highs and too lows” such as in blood pressure, etc. He says he operates on the view that the purpose of being a doctor is to improve health in dramatic ways, which he adds should be measured.

He has a slide up of several examples of aging patterns: “pause,” “decline in,” and “onset age.” One example is “osteopause,” “bone sensity” and “30”, or “menopause,” “estrogen, progesterone, and testosterone in women” and “40.”

Brain aging, from his perspective, has to be simplified to get anywhere. He “boils down” to loss of neurotransmitters and hormones in aging that leads to widespread down.

“Aging is marked by neuropsychatric decline,” he says, along with other factors involving neurotransmitters and hormone loss.

Lots of hormones are involved in aging. The hormone changes FSH and LH go up, leptin goes up, insulin up, but insulin growth factor, DHEA, vitamin D, testoterone, estradiol all go down.

Age 30 – HGH, IGF-1,3 deficiency
Age 40 – Testosterone, estrogen deficiency
Age 50 – DHEA, thyroid deficiency
Age…

Braverman is going to focus on leptin now. First thing to not forget is that it’s both an adipose hormone and a hypotholamic hormone. It’s an integral component of energy homeostasis and body weight regulation.

There’s a close interaction also with leptin and dopamine D2 receptors, as well as other genes involved that are associated with high BMI.

“Leptins are kind of funny because when they go low they’re associated with dementia in aging,” he says. “Ironically, on the other side, high leptins in obesity are correlated with decreased testosterone, estrogen as well.”

Leptin impinges on many brain areas in addition to the hypothalamus. If you have a sick body, you have a sick brain.

But let’s talk about obesity, he says, it’s what kills you, speeds up the aging process and reduces lifespan by 15 years. One of five brain problems costing the country at least a hundred billion or more is obesity, addiction, neuropsychiatric problems, violence and cognitive impairments.

There should be more awareness between the distinction of Normal-Weight Obesity and Overweight-Obesity.

“I really see muscle mass as critical,” he says. “If you’re thin and flabby,” all the bad things that come with obesity are coming for you any way including metabolic syndrome (increased triglycerides, increased LDL, lower HDL, etc.).

He likes the DEXA scan much better than BMI. In fact, he had a few slides on this topic. But that’s a different story. In summary, he says, “the obesity epidemic is much worse than we think.”

Aging is marked by “metabolic imbalances,” then shares a little poem which he calls the “Description of Aging.”

Your brain ages when
you burn up
you dry up
you swell up
you turn to stone
you get choked by death
you rust…

So, finally, now he is discussing potential agents that will increase leptin sensitivity and lower leptin levels. It’s a long list (but I only got to two):

-vitamin D
-fish oil
-herbal supplements

There’s some drugs too:

-Altace
-Lipitor
-Byetta
-Glucophage
-nicotine
-etc.

Lifestyle effects:

-7 hrs sleep each night
-smoking
-bariatric surgery
-physical activity
-decreased stress

Hormones:
-high testosterone
-increased DHEA
-lower estrogen

Gosh, there are a lot of agents:

– elevated TGs
-Hypercaloric diets rich in SFA or PUFAs

He’s going to summarize that obesity epidemic speeds up aging, leptins play a role (it’s the “connection between the brain and fat cells”), and there’s a synergistic effect dopamine, acetylcholine, GABA and serotonin that is the “Brain and Body Connection.”

We can emphasize brain and body repair mechanisms with the “four horesemen”: Natural, pharmaceutical, hormonal and lifestyle agents to promote the synergistic action of dopamine, acetylcholine, GABA and serotonin.

He’s got a whole table with several agents. I see caffeine on there, which is what I think I need, plus fish oil, acetyl carnitine, CoQ, theanine, tryptophan, magnesium, folic acid, etc.

“If we’re going to keep our intelligence with age, we’re gonna have to have neurogenesis,” he says. “I was taught that there was one neurotransmitter in one neuron. Now we know that there are 70 neurotransmitters in a neuron.”

—

For such an interesting title, not sure this talk delivered. I guess I was hoping for a step-by-step on how to prevent and reverse brain aging. But, diet and exercise, eating lots of natural agents and pharmaceuticals seems to be the key.

Helping the Brain Help Itself keynote by Mark Mattson

Now, for the second keynote at American College of Nutrition conference in New York City we’re listening to Mark Mattson, Ph.D. He starts out talking about his work in the laboratory of neurosciences at National Institutes of Aging.

He talks about what happens during aging in the brain.

More and more as people get older, neurons age and die, predisposing us to Alzheimer’s and other brain diseases. The mechanisms on how this happens are being shown and he discusses the different pathways.

Dietary energy restriction, exercise, cognitive enrichment promote neuroprotection (hormesis?) by reducing oxidative stress and inflammation.

Current trends in Alzheimer’s showing it’s a huge issue that’s not being dealt with. We need a war on it like we have on cancer. Many people die from Alzheimer’s and it’s a tax on society.

He discusses amyloid plaques and neurofibrillary tangles (with tau) that is involved in AD pathogenesis.

There’s a number of animal models for AD such as transgenic mice with overexpression of mutated amyloid-precursor protein. Also, PS1 mice.

Mattson manipulates diets of AD-prone mice to see how diet affects their cognitive function, memory, and amelioration of AD behavior.

Intermittent fasting and calorie restriction ameliorated AD behavior changes. He thinks that neurons can be stimulated by these diets to protect themselves against the amyloid protein. He shows us data on how CR reduced tau levels, but IF did not.

They also used “couch potato mice” model of AD: overfed, sedentary. Of course, these are great controls.

CR and IF showed gene expression in the brain (Martin et al, 2007, Endocrinology).

They wanted to show an effect in primates, so performed a study in rhesus monkeys. They took the monkeys and reduced their calories by 30 percent for 11 months. They tested their motor function, dopamine. They injected a toxin called MPTP.

Both the animals on the normal diet and CR diet had deficits in motor function, but CR had less seeming to have a protective effect from a functional endpoint. When measured for dopamine, there was major depletion in the striatum in both. When measured for BDNF, the CR had higher levels of BDNF.

In a stroke model, they took young, middle-aged, or old mice on either IF or normal diets. They then damaged the cerebral cortex and measured neurological deficit. There was significant benefit for the young and middle-aged mice on IF, but not in old.

“So start early,” he says. Exercise, eat less when you’re younger to prevent Alzheimer’s in the future. IF reduced inflammation in the young and middle-aged, but not in old.

Mattson starts talking about type 2 diabetes now. The world prevalence of diabetes is rising. This disease leads to problems later on in the brain, as shown in more mice models (like leptin-receptor mutant mice), which he summarizes.

– reduced BDNF levels
– l wer neurogenesis

Diabetes reduces neurogenesis, but what about interactions with exercise or calorie restriction? Both exercise and CR increase BDNF levels.

Mattson talking about possibility of using drugs and phytochemicals now (Duen et al 2004; Nelson et al 2007).

Some drugs work by involving BDNF. There are also several fruits and vegetables, but he doesn’t think they have an intrinsic factor as antioxidants. Instead, he said, they have toxins concentrated in the skin meant to repel insects. Lots of these plants have natural pesticides, so Mattson acquired many of these natural chemicals to see which produce resistance to neurogenerative disorders.

OK, back to talking about IF, this time about a study showing that IF improves cardiovascular risk factors under stress in animals.

-The body temperature is up on the feeding day, down low on the fasting day.
-Heart rate variability was measured too. Higher heart rate variability is a good thing, because it shows adaptability. IF improved heart rate variability.
-Higher levels of BDNF

Interesting thing, he notes, when they infused BDNF in mice, they showed better heart rate variability.

Human studies? Mattson talks of Jim Johnson’s work on subjects with moderate asthma on alternate-day calorie restriction. The subjects adapted to the diet, lost bodyweight, their mood increased, but importantly their asthma improved.

Mattson begins discussing GLP1, a receptor that when stimulated reduces amyloid plaque accumulation, and drugs that stimulate it. GLP1 increases BDNF and insulin sensitivity.

He intends to conduct a 3-year double-blind, randomized trial on a drug (Exendin-4) to treat Alzheimer’s disease, by testing CSF biomarkers. He is optimistic and says at least he knows the drug should help with blood glucose management.

—

Unfortunately, Mattson ran out of time, but the presentation was awesome! Good to know we have serious scientists like this working on AD.

Surprisingly, with all the talk about CR, IF and Alzheimer’s, not a word was said about Sirtuin 1 activation, so I asked Dr. Mattson his opinion on the research, specifically Guarente’s paper showing that SIRT1 activation inhibited two pathways in the progression of AD.

Mattson responded with a dose of skepticism about sirtuins and their potential, at least as a treatment in the diseased state when they’d use up a lot of NADPH at a time when the brain needs it.

hmm…

Location:E 103rd St,New York,United States

High doses of B vitamins slow rate of shrinking brain

Unfortunately, getting older comes with a common consequence affecting up to 16 percent of elderly people – gradual reduction in brain size, which is associated with problems in learning and memory. However, a new study reports that daily supplementation with high doses of B vitamins may help slow the rate of brain degeneration.

Oxford researchers gave 168 individuals over the age of 70 supplements containing high doses of folic acid (0.8 milligrams per day), B6 (20 milligrams per day) and B12 (0.5 milligrams per day), or a placebo as part of a randomized, double-blind controlled trial. Then, following two years of the supplementation program, the participants’ brains were assessed using serial volumetric magnetic resonance imaging scans.

The researchers reported their results in the September issue of PLoS One: the rate of brain shrinkage, or atrophy, in the group taking the supplements was 53 percent lower in comparison to the group taking the placebo. Their conclusion was that the high doses of B vitamins slowed the rate of brain shrinkage in elderly with mild cognitive impairment.

According to the authors, however, it is still unclear which vitamin provided the greatest benefit for the brain. They found that the reduced rate of brain atrophy was a result of an increase in either vitamin B12 status or folic acid status, but could not conclude which of the two “vitamins is the most important.”

They added that vitamin B6 may be less important for brain health since there was a, “lack of association of atrophy with the change in cystathione levels, a marker of vitamin B6 status.”

Folic acid and vitamin B12 play a role in protecting the brain, most likely because their presence helps to lower the concentration of the amino acid homocysteine in plasma. Higher levels of homocysteine are a risk factor associated with smaller brain size as well as problems with learning and memory — as well as related to poor heart and cardiovascular health.

The study adds to emerging evidence that supplementation with B vitamins may be a convenient way for elderly to help support memory and learning.

Source: Smith AD, Smith SM, de Jager CA et al. Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial. PLoS One 2010;5:e12244.