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."

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.

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."

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.

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.