Study: Reducing Dietary Protein, Especially From Animal Sources, Is “Highly Effective In Inhibiting Tumor Growth”

Switching from animal proteins to plant proteins was also found to inhibit tumor growth. Lentils and beans are one of the best sources of plant protein.

Dietary Protein Restriction Inhibits Tumor Growth In Human Xenograft Models Of Prostate And Breast Cancer, Oncotarget, December 2013

This is from their introduction, which typically includes a literature review:

Prostate (PCa) and breast (BC) cancers are the most commonly diagnosed cancer in men and women living in Western countries [1]. Studies of populations migrating from low- to high-risk areas have shown a steep rise in PCa and BC rate [2,3]. In addition, in the last three decades the age-standardized PCa and BC incidence and mortality rate has increased dramatically in Japan and Singapore, two developed countries previously considered having a very low prevalence rate [4,5]. These studies strongly suggest that environmental factors play a key role in PCa and BC pathogenesis. It has been hypothesized that this increased prevalence of PCa and BC is partially due to the radical dietary shifts from traditional to Western diet patterns [2,6], which are characterized by high intakes of animal protein and fats, and refined carbohydrates.

Data from epidemiological and experimental studies indicate that protein intake is one of the most important dietary regulators of circulating levels of IGF-1, a powerful growth factor, which activates the Akt/mTOR pathway [7,8]. High circulating levels of IGF-1 are associated with increased risk of PCa and BC [9-11], Moreover, multiple lines of evidence have shown that activation of the PI3K/AKT/mTOR pathway, through insulin/IGF-1 stimulation and/or high levels of essential amino acids, play a crucial role in maintaining the malignant phenotype, and its inhibition antagonizes growth and motility of a range of cancer cells in mouse models [12-17].

They found:

  • 70% inhibition of tumor growth in the prostate cancer model.
  • 56% inhibition in the breast cancer model.

When fed:

  • 7% protein diet when compared to an isocaloric 21% protein diet.

Animal protein was more cancer-promoting than plant protein:

  • We observed that modifications of dietary protein quality, independently of protein quantity, decreased tumor growth. A diet containing 20% plant protein inhibited tumor weight by 37% as compared to a 20% animal dairy protein diet.

They concluded:

Our findings suggest that a reduction in dietary protein intake is highly effective in inhibiting tumor growth in human xenograft prostate and breast cancer models, possibly through the inhibition of the IGF/AKT/mTOR pathway and epigenetic modifications.

It’s not genes. It’s diet.

One Meal Of High Saturated Fat Rapidly Increases Liver Fat And Insulin Resistance

I know you know this, but it’s always worth posting new studies so we know that the science hasn’t changed:

Acute Dietary Fat Intake Initiates Alterations In Energy Metabolism And Insulin Resistance, Journal of Clinical Investigation, 23 January 2017

This study demonstrates that a single oral dose of saturated fat increases hepatic TG [triglyceride] accumulation, insulin resistance, GNG [gluconeogenesis], and ATP concentrations in the human liver. Ingestion of saturated fat also induces peripheral insulin resistance in skeletal muscle and adipose tissue.

One fatty meal. One. Note that the people who received the fat meal, which did not include any carbohydrate, experienced a rise in blood glucose and blood insulin. That’s because the liver started pumping out glucose (that it was making from gluconeogenesis, which uses bits of the body’s protein, which it steals from things like muscle).

This was a German study.

Our Brain Is Expensive To Run, Uses Nearly A Quarter Of The Calories We Take In, All Carbohydrate

This quotation is from the book I’m reading, Other Minds. The Octopus, The Sea, and The Deep Origins of Consciousness:

Neurons cost a great deal of energy to run and maintain. Creating their electrical spasms is like the continual charging and discharging of a battery, hundreds of times each second. In an animal like us, a large proportion of the energy taken in as food, nearly a quarter in our case, is spent just keeping the brain running.

Is that right? A quarter of our food? I found it corroborated here: Why Does the Brain Need So Much Power?, Scientific American, April 2008

It is well established that the brain uses more energy than any other human organ, accounting for up to 20 percent of the body’s total haul.

That article went on to say that electrical impulses aren’t the only thing the brain does with those calories:

Until now, most scientists believed that it used the bulk of that energy to fuel electrical impulses that neurons employ to communicate with one another. Turns out, though, that is only part of the story.

Two thirds of the brain’s energy budget is used to help neurons or nerve cells “fire” or send signals. The remaining third, however, is used for … “housekeeping,” or cell-health maintenance.

Housekeeping includes things like ATP production (ATP, adenosine triphosphate, is a chemical storage form of energy), movement of ions across membranes, cell division, production of neurotransmitters and receptors. Lots of metabolic processes.

The brain is a hungry and demanding organ. And you know what it eats? Glucose. Almost exclusively:

Glucose is virtually the sole fuel for the human brain, except during prolonged starvation. The brain lacks fuel stores and hence requires a continuous supply of glucose. It consumes about 120 g daily, which corresponds to an energy input of about 420 kcal (1760 kJ), accounting for some 60% of the utilization of glucose by the whole body in the resting state.

Fatty acids do not serve as fuel for the brain, because they are bound to albumin in plasma and so do not traverse the blood-brain barrier. In starvation, ketone bodies generated by the liver partly replace glucose as fuel for the brain.
Biochemistry. 5th edition. Berg JM, Tymoczko JL, Stryer L. 2002.

The brain doesn’t store fuel like muscles and other organs do. It needs a constant supply of glucose, always flowing in. Other organs will sacrifice to keep the brain running. If carbs (which supply glucose) are limited in the diet, the liver can produce some, along with ketones, but eventually the body will begin to break down its muscle to supply glucose for the brain.

Superb Owl Sunday

Go to The Atlantic for their photographic essay celebrating superb owls. (Click to enlarge.)

An owl in flight. CC BY v2 Geoff Sloan https://www.flickr.com/photos/gsloan/8705467989/

A burrowing owl rests on the ninth hole of the Olympic golf course near its nest in a sand bunker during a practice round for the 2016 Summer Olympics in Rio de Janeiro, Brazil, on August 5, 2016.

A pair of Great Grey Owls or Lapland Owls sits inside an open air cage at the Royev Ruchey zoo in Russia’s Siberian city of Krasnoyarsk, on October 6, 2011.

Mutual curiosity:

Boulder County Sheriff’s Deputy Sophie Berman crouches over a small owl, for a brief encounter before the bird flew away, near Rainbow Lakes, outside Nederland, Colorado, on July 21, 2015

Ending Racism And Economic Inequality Should Be A Goal Of Public Health

Ms. James, a former factory seamstress. From: 28% Of Philadelphia’s Population Live Below The Poverty Line

I tried to pare this article and just post some kernels but the author (@JamesHamblin, MD and senior editor of The Atlantic) pared it down already.

Why Succeeding Against the Odds Can Make You Sick, James Hamblin, New York Times, 27 January 2017
For African-American strivers, hypertension and other health problems may be linked to racism, not race.

If there is any kernel, it’s my title. But here are some pieces anyway:

Gene Brody, a professor at the University of Georgia … and colleagues recently analyzed the socio-economic backgrounds and personalities of the people in the Pittsburgh study and found that those who were “more diligent and tended to strive for success” were more likely than the others to get sick. To Dr. Brody, the implication was that something suffers in the immune systems of people who persevere in the face of adversity.

In 2015, they found that white blood cells among strivers were prematurely aged relative to those of their peers. Ominous correlations have also been found in cardiovascular and metabolic health. In December, Dr. Brody and colleagues published a study in the journal Pediatrics that said that among black adolescents from disadvantaged backgrounds, “unrelenting determination to succeed” predicted an elevated risk of developing diabetes.

The focus on black adolescents is significant. In much of this research, white Americans appeared somehow to be immune to the negative health effects that accompany relentless striving. As Dr. Brody put it when telling me about the Pittsburgh study, “We found this for black persons from disadvantaged backgrounds, but not white persons.”

In the United States, gaps in health and longevity between the wealthy and the poor are some of the greatest in the world … But decades of research show that when resilient people work hard within a system that has not afforded them the same opportunities as others, their physical health deteriorates.

The effect has become known as John Henryism.

Why would white people appear to be immune? … Her conclusion is that because African-Americans encounter more overt and systemic discrimination, “the combination of adversity and high-effort coping is what’s having health consequences.”

Going forward, John Henryism is likely to affect other races, other groups:

Globally, there is no association between skin color and the length of one’s life. This is an American phenomenon. In medical school we are taught that black men are much more likely than other patients to have hypertension, as if this were simple biology.

“There’s very little genetic basis for hypertension,” said Dr. Mujahid. “It’s much more about social context and lifestyle.”

And that social context is now changing in the United States.

“Because African-Americans experience so much more exclusion and degradation — something that working-class whites didn’t experience at the time — that probably created conditions that were ripe for us to only see the effects in blacks,” Dr. James said about his research in the ’80s. “But now white Americans are experiencing a great deal of economic — and, dare I say, psychological — pain because of their dislocation as a result of powerful macroeconomic forces.”

Dr. James expects John Henryism can now be seen across Western democracies, wherever people are inculcated with a Protestant sense of personal responsibility and belief in self-reliance. “When people act on that — really trying to make ends meet going up against very powerful forces of dislocation — their biological systems are going to pay a price,” he said.

“That’s the situation African-Americans have been in since the beginning,” he added. “Now we’re seeing other groups begin to be exposed to these same forces.”

In the spirit of the original John Henry, among those forces is technologically induced unemployment. The mechanization of labor once pushed rural Southern blacks into the factories of the North. Now mechanization is giving way to automation, affecting less-educated white Americans, especially men.

The answer? Work towards ending racism and building the middle class:

The Trump administration could do much more to damage Americans’ health than just repeal the Affordable Care Act and leave people without access to hospitals and medications. “The consequences around the divisiveness, and increased instability and uncertainty for families and children, combined with increased racial tension and overt acts of discrimination,” Dr. Mujahid noted, all stand to heighten the John Henryism effect.

“What we want is for people who overcome so much to achieve the American dream to have the health to enjoy the fruits of their efforts,” said Dr. Brody. “Right now that doesn’t seem to be happening.”

Or maybe people should simply have to overcome less in the first place — to have something close to equal opportunity to succeed. But as the middle class contracts and wealth gaps expand, the promise of equal opportunity seems to be receding.

John Henryism. If I use that term in the future, you’ll know what I mean.

It isn’t just the food we eat, or whether we smoke or drink or use drugs or don’t sleep enough or fail to stay active; it’s how effective our immune system is and how much it’s put upon that contributes to health. This makes ending racism and economic inequality a goal for public health.

Substances In Environment That Increase Risk For Alzheimer’s Disease

A diet low in animal foods reduces risk for Alzheimer’s disease.

More from:

Unified Theory Of Alzheimer’s Disease (UTAD): Implications For Prevention And Curative Therapy, Journal of Molecular Psychiatry, 2016

Any successful Alzheimer’s Disease (AD) therapy … must include the removal of any type of environmental toxin that might inhibit AHN and entertain and aggravate the disease process.

* AHN is Adult Hippocampal Neurogenesis, the ongoing formation of nerve tissue in the brain’s hippocampus from stem cells, throughout life, which I didn’t even know we could do.

Here’s the list of the chemicals they say we should limit our exposure to, and why:

Tobacco smoke diminishes AHN and promotes gliogenesis in rats [499]. Hence, heavy smokers (2 packs a day) have a 2.6 fold increased AD risk [500]. But also electronic cigarettes, even if they would only contain nicotine as an ingredient (which they do not), are unhealthy and most likely AD-promoting, as nicotine impairs neurogenesis and plasticity of hippocampal neurons [501].

Alcohol intake of two drinks or more per day accelerates AD by about 2 to 3 years and, when combined with heavy smoking (20 cigarettes per day) by about 4 to 6 years. And for those, carrying an ApoE4 allele, which aggravates the consequences of unhealthy lifestyle choices (as detailed above), the onset of AD is on average 10 years earlier [502]. High alcohol intake was shown to efficiently block AHN in an non-human primate model, with the effect lasted for 2 months even after alcohol discontinuation [503]. The lasting alcohol-induced reduction in AHN paralleled an increase in neural degeneration by nonapoptotic mechanisms. Interestingly, abstaining from alcohol was also seen as a risk factor in the past [504], but this finding has not been confirmed [505]. Hence, drinking small amounts of alcohol might not be statistically harmful, but most likely does not decrease the risk of developing AD.

Trans fatty acids (TFAs), either from processed food (fried products and many fast-food sources) or from whole-fat dairy and ruminant meat products are implicated in AD [506]. Both sources were shown to equally efficiently increase low density lipoprotein (LDL)-cholesterol [507] and cause negative health effects [508]. TFAs drive the mortality risk from cardiovascular diseases [509] and increase the rates of cognitive decline in the elderly, again, irrespective of the source [510, 511]. Epidemiological studies starting with healthy participants showed that TFAs raise insulin resistance, blood pressure and cause also chronic inflammation [508], all well accepted causal risk factors for AD. Furthermore, TFAs inhibit the conversion of n-3 PUFAs into DHA, limiting their accumulation in the brain [512]. DHA depletion has been shown to result in decreased BDNF levels [513], in impeded productive AHN [514] and in neuroinflammation [308]. A recent in-vitro study provided convincing evidence that TFAs increase amyloidogenic processing of the amyloid precursor protein (APP), resulting in an overproduction of Aβ [515]. Moreover, TFAs were shown to enhance the oligomerization and aggregation of Aβ. Taken together, high intake of TFAs, independent of the source, might increase the AD risk by many avenues, also causing an earlier onset of the disease.

Nitrosamines cause deficits in motor function and spatial learning, as well as neurodegeneration characterized by lipid peroxidation, increased levels of Aβ and p-tau, neuroinflammation and neuronal insulin resistance [516]. Nitrosamines are found in tobacco smoke. Significant levels of nitrosamines are also produced from nitrites and secondary amines found in many products, like processed meat and cheese preserved with nitrite pickling salt. This is another reason to avoid (mass produced) meat or cheese products.

Bisphenol A (BPA) leads to unwanted hormonal activity and was shown to impair AHN, spatial learning and memory [517]. BPA is found in a variety of common consumer goods like water bottles. Epoxy resins containing BPA are used to line water pipes and for coatings on the inside of many food and beverage cans. Exposure to other bisphenols (B-Z) that are used as replacements (in order to advertise BPA-free products) show similar detrimental effects [518]. Hence BPA-free products are not necessarily safer and support the removal of all bisphenols from consumer merchandise [519].

Pesticides: Roundup (a glyphosate-based herbicide) was recently shown to increase the lipid-peroxidation, glutamate excitotoxicity and oxidative damage in the hippocampus [520]. The widely used pyrethroid pesticide deltamethrin induces apoptotic signalling in the hippocampus and impairs AHN [521]. Similar effects were observed for Carbofuran, a carbamate pesticide [522]. These neurotoxic effect of widely used chemicals in conventional agriculture argues for the use of organic produced products for the prevention and the treatment of AD [4].

Aluminium might act as an accelerator of the progression of [523]. Aluminium enhances pro-apoptotic signalling, reduces BDNF in the hippocampus and negatively affects spatial learning in animal models. In fact, every biochemical function in brain cells appears to be affected by aluminium (reviewed in [2]). In addition, aluminium may play crucial roles as a cross-linker in Aβ oligomerization [524]. Taken together, aluminium exposure should be avoided in prevention and treatment of AD.

Methylmercury (MeHg) competes with selenium for its enzymatic binding sites and acts as a highly specific and irreversible inhibitor of selenoenzymes, which are required to prevent and even reverse oxidative damage throughout the body, in particular the nervous system. Inhibition of selenoenzymes appears to be the proximal cause of the pathological effects known to accompany MeHg toxicity [525]. Dietary selenium intake is inversely related to vulnerability to methylmercury (MeHg) toxicity, which explains why maternal ingestion of foods that contain MeHg in molar excess of Se has adverse child outcomes, whereas eating MeHg-containing but selenium-rich ocean fish results in improved child IQs [526]. Similarly, MeHg intake impairs hippocampal development and AHN [527] and is associated with delay in cognitive development [528] and AD [529]. Nevertheless, a recent study showed seafood consumption was associated with less AD neuropathology despite the increased mercury levels [58]. This controversial result might be explained by the fact that both DHA and selenium are contained in high concentration in seafood. Interestingly, in this study, ApoE4 carriers profited most of high seafood intake, or conversely, ApoE4 carriers are more harmed by a deficit in DHA and/or selenium consumption. Taken together, a diet low in MeHg is advised, but at least as important is a diet that keeps selenium and n-3 PUFAs (DHA and EPA) levels sufficiently high.

Iron is essential for many metabolic processes, but, when left unregulated, is implicated as a potent catalyst of reactive oxygen species generation. Iron complexes with ferritin, the major cellular storage of this transition metal [530]. As outlined above, increased ferritin levels in the cerebrospinal fluid (CSF) are negatively associated with cognitive performance and predicted speed of MCI conversion to AD. Since ApoE4 (in contrast to ApoE2 and ApoE3) enhances iron uptake into the brain [59], carriers who consume large amounts of iron-rich animal products are particularly susceptible to elevated brain iron, enhanced ROS production and AD progression. This might be one of the reasons, why a diet low in animal products reduces AD risk; and pesco-vegetarians have the lowest mortality when compared to other common diets [531]. Individuals with MCI and high CSF-ferritin levels might delay conversion to AD by as much as 3 years by taking a chelating drug like deferiprone [532], according to the authors of the above mentioned CSF-ferritin-study. An alternative option with less side effects is treatment with α-lipoic acid (ALA) [533], which was shown to be highly effective in reversing oxidative stress arising from iron overload [534]. Due to the multitude of additional useful properties of ALA for the treatment of AD, ALA will be part of a therapeutic scheme suggested below.

Copper like iron is an essential element for human growth and development. And likewise, excessive intake which leads to free copper contributes to neurotoxicity and impaired spatial memory by specific changes in the expression of synaptic proteins and hippocampal signalling pathways, which causes oxidative stress and neuronal apoptosis [535]. Inorganic copper from drinking water can be directly absorbed and elevate the serum free copper pool, thereby attributing to AD progression [536]. In case of high free copper levels, three regimens are advised: (1) Avoiding water contaminated with copper and supplements, (2) restoring normal zinc levels, as it was shown that elevating zinc levels significantly reduced serum free copper in AD patients [3] and (3) treatment with free copper-lowering ALA [537], as will be discussed in more detail below.

Medications: Use of gastric acid inhibitor was significantly associated with the presence of vitamin B12 deficiency [538], a risk factor for AD. Meanwhile, it was found that these drugs increase the levels of Aβ in the brains of mice and are association with an increased risk of dementia in humans [539]. Increases in incident dementia are associated with long-term use (over three years) of anticholinergic drugs like for example the tricyclic antidepressant doxepin, the antihistamines chlorpheniramine and diphenhydramine, and bladder control drugs like for instance oxybutynin [540]. A case–control study showed an association between the use of benzodiazepines (used for sleep and anxiety control) and the risk of AD [541]. A recent study provided evidence that memory and hippocampal architecture of WeDi-treated rats was particularly vulnerable to short-term treatment with the benzodiazepine midazolam [542]. Again, this short number of examples must suffice to show that there is always the chance that artificial chemicals like many commonly used drugs might interfere with the complex pathomechanisms outlined by the UTAD, thereby increasing AD risk.

I didn’t know that eating dairy and red meat inhibits the conversion of omega-3 PUFAs (short-chain, like in flax seed) into DHA (long chain, like in fish oil), and that it is the trans fatty acids in them which does this. You would need to control for meat-and-dairy eating, and for other sources of trans fats, if you wanted to investigate this conversion. I haven’t seen that done.

Many of these substances (iron, mercury, pesticides, nitrosamines, trans fatty acids) are found in higher amounts in diets that contain a lot of animal foods. Perhaps that is why “a diet low in animal products reduces AD risk.”

This is a great list. We need a public health campaign that seeks to limit exposure to these substances if we are to stem the rising tide of brain diseases. Let us hope that our new President prioritizes this effort.