Tuesday, July 20, 2010

Middle to Late Paleolithic: Neanderthals Consumed Grains and Legumes

For 200,000 Years Neanderthals Dominated Euroasia

Homo neanderthalensis, Neanderthals, migrated out of Africa and completely separated genetic lineages an estimated 200 to 300,000 years ago or even longer. Recent genetic data has shown that as Neanderthals migrated northward, hypopigmentation and red hair (MC1R gene associated) characteristics may have been selected for. National Geographic presents a nice summary HERE.

The geographic range for Neanderthals was vast from Germany, France, Croatia, the steppes of Russia, the Mediterrean shores where they hunted seal and mussels to the Middle East and Israel. See wiki diagram. This area also included the 'fertile cresent', the origin of mass cultivation of cereal grains and domestication of herd animals that sprouted the new world economy, war, arts and advanced culture.

Modern Humans Slowly Entered Eurasia 100,000 Yrs Ago

Modern humans (aka Hss or Homo sapien sapien) started to arrive 90 to 100,000 years ago according to fossil evidence from a rock shelter in Qazfeh Israel. See diagram, courtesy National Geographic). Perhaps after separation from a common hominid ancestor 200 to 300,000 years earlier, modern homininds and Neanderthals crossed paths and recent genomic evidence suggest intermingling occurred... though probably rarely but appears to have resulted in introgression of 1-4% Neanderthal DNA in Euroasian gene stock. The Neanderthal clade consisted of an estimated sparse 15,000 individuals. Earth's population was probably only double or triple that? The last remains of Neanderthals are dated back 28,000 yrs ago at Gibraltar.

What happened? No one is sure...

Sexual and DNA Neanderthal + Modern Human Admixture

Trinkaus, a paleoanthropologist interviewed in the National Geographic piece, states "At the time of the biological transition, the basic behavior [of the two groups] is pretty much the same, and any differences are likely to have been subtle." Trinkaus believes they indeed may have mated occasionally. He sees evidence of admixture between Neanderthals and modern humans in certain fossils, such as a 24,500-year-old skeleton of a young child discovered at the Portuguese site of Lagar Velho, and a 32,000-year-old skull from a cave called Muierii in Romania. "There were very few people on the landscape, and you need to find a mate and reproduce," says Trinkaus. "Why not? Humans are not known to be choosy. Sex happens."

Euroasian Fauna and Flora Based on Fluctuating Temperature

See far top diagram, courtesy Wiki. Wild temperature fluctations occurred on earth during the time period that Neanderthals inhibited Euroasia. Mega and minor extinctions of flora and fauna would probably in a single lifespan of a Neanderthal's life. As the temperatures cooled, trees retreated and grasslands persisted and greatly expanded in their territorial ranges. As the Ice Age ended, the Neanderthal had already perished as a distinct genetic species. Around ~12,000 years ago when high temperatures occurred consistly, mass cereal cultivation and domestication of animals signaled what we recognize now as the Neolithic age. How early were the first small grained grasses foraged by our hunter-gatherer forebears?

Would this have affected Neanderthal gene expression?

Chronic disease afflictions?

Natural selection?

Evidence Middle Paleolithic Neanderthals Foraged Small Grained Grasses

Grasses are basically weeds and non-flowering. The seeds are dispersed off the grain-head by wind and animal/bird ingestion. As such, natural plant defenses support dispersal by keeping the seed intact and evolution of 'chemical warfare' involving phytic acid, lectins and gluten to ensure intact dispersal after animal/bird digestion. As early as 105,000 years ago, sorghum grains were found immediately near hearths in S. Africa highly suggestive of ancient man foraging and use stone mill tools (Science 2009). Could ancient Neanderthals have adopted similar tools and techniques, especially if cooling climatic changes, reduced animal resources to hunt and possible competition with modern humans for resources were all occurring?

Apparently this is the case. ~Approximately 50,000 yrs ago, definitely before the end of the middle paleolithic era, evidence for Neanderthals collecting phytic acid rich legumes and small-grain grasses exists.

Weiss et al published in a review of the use of cereals out pacing small-grained labor intensive grasses in utilization by early man (PNAS 2004). See above diagram. I extrapolated to where estimated Neanderthal extinction may have occurred and the potential for use of small-grained grasses by co-mingling modern humans. He discusses the evidence of grain/cereal foraging by Middle Paleolithic Neanderthals at 2 sites in the Middle East ('fertile cresent'):
  • 48-60,000 yrs ago: Kebara Cave, Lev et al
  • 55-70,000 yrs ago: Amud Cave, Madella et al

    Middle Paleolithic: Prelude to the Broad Spectrum
    In Middle Paleolithic Kebara Cave (~60,000–48,000 thermoluminescence years ago), Mount Carmel, Israel, Lev and associates (41, 44) found 3,956 charred seeds representing 52 taxa. On the basis of ethnographic observations and the fact that this plant assemblage was retrieved mainly from the immediate environment of the hearths, we assume that these seeds represent the Mousterian cave dwellers’ diet. Most of the seeds (3,300) were legumes but there were also acorns (Quercus sp.) and pistachio (Pistacia atlantica) nuts, as well as the seeds of giant golden-drop (Onosma gigantean), podonosma (Podonosma orientalis), Judean bugloss (Echium angustifolium judaeum), safflower (Carthamus sp.), and wild grape (Vitis vinifera). Only ten grass grains, including two of wild barley (Hordeum spontaneum), were recovered. In light of the generally good preservation of plant remains in the cave, Lev and colleagues concluded that cereal grains were an insignificant food source. It is notable, however, that they had made their way into human hands by this time, albeit in modest amounts.

    Less compelling evidence of the Middle Paleolithic diet comes from Amud Cave (~70,000–55,000 thermoluminescence years ago) in the Upper Galilee, Israel. On the basis of phytolith assemblages, Madella et al. (42) concluded that the cave’s Neanderthals exploited herbaceous plants, ligneous parts of trees and shrubs, and mature grass panicles, and proposed that broad-spectrum exploitation of plants had started at least by the end of the Middle Paleolithic.

Legume and Grain-Consuming Neanderthals and Modern Humans

Did Neanderthals' diet affect the trajectory of their long existence to a final conclusion earlier than expected for such a strong, vital, muscular, close-proximity large-game hunting, cold-adapted, smart, larger-brained (20%), advanced hominid race who had already survived several large and small ice ages???

Why did their race slowly but abruptly fall short?
Lectins? Phytates? Vitamin D deficiency? Celiac disease?
How are both modern humans and extinct Neanderthal similar to Old and New World Primates in regards to pathophysiology of celiac and bone diseases?
See diagram below -- fossil sites of Neanderthal and modern man and the fertile cresent of grains/cereals/gluten. The vegetation is for 18,000 yrs ago, not 28,000 yrs ago when it was several magnitudes cooler reaching the lowest temperatures of the last Ice Age, more grass-lands and arid areas in the Mediterrean and northern European areas... The intense cooling from the Ice Ages did not initiate at polar caps but central continental bodies of water -- literally sucking out 200 to 300 ft of water as it cooled to freezing. Vegetation vastly altered... Grains...d*mn dirty grains...

Next post:
Evidence of Phytate-related Rachitic Damage in Late Neanderthals

Courtesy of owners at handprint.com

Monday, July 19, 2010

Meat Science: Meat and Omega-3 as ACE-Inhibitors

T. Colin Campbell: No Longer Pied-Piper?

So... Again the data speaks volumes and the diminutive Ms. Mingers has put the final dagger in the vegetarian-low-sat-fat-fairy tale spun by so-called academic Campbell. The action is here: The China Study, My Response by Denise Minger.

You know if my teeth, eye color and health were ruined by a low saturated fat, low cholesterol, no meat, high soy, high grain vegetarian diet... I'd be mildly pissed.

And hungry...

For M-E-A-T . . . !

Meat Science

Added to NCBI PubMed in Feb, this newer journal features research and science in MEAT. I came across two articles here regarding protein from meat and beef which behave as ACE-inhibitors, one of the drugs deployed for hypertension, afterload reduction in heart failure and kidney protection in Type 1 (T1)and Type 2 diabetes (T2D) individuals. The mechanism of action of these drugs is blocking a pro-inflammatory-associated enzyme known as angiotension converting enzyme, ACE. Many peptides (proteins that are short sequences) are found in animal, seafood and plants that we consume that, in fact, have ACE-inhibitory action in mammalian systems. Even breastmilk contains lactoferrin which may inhibit ACE.

(1) A review of meat protein hydrolysates and hypertension.
Ahhmed AM, Muguruma M.
Meat Sci. 2010 Sep;86(1):110-8.

(2) Purification and identification of angiotensin converting enzyme inhibitory peptides from beef hydrolysates
A. Jang and M. Lee
Meat Science, Volume 69, Issue 4, Pages 653-661.

Clinical M-E-A-T Series *haa*:
o Meat as Medicine: Grassfed v. Conventional
o Phytanic Acid in Grassfed Meat: Binds PPAR-α and RXR (potent anti-inflammatory controls)

Other related meat science and research:
o Antihypertensive Activities of Peptides Derived from Porcine Skeletal Muscle Myosin in Spontaneously Hypertensive Rats
o Novel Angiotensin-Converting Enzyme (ACE) Inhibitory Peptides Derived from Boneless Chicken Leg Meat
o Antihypertensive effects and endothelial progenitor cell activation by intake of chicken collagen hydrolysate in pre- and mild-hypertension. [Endothelial progenitor cells are required for cellular and organ regeneration -- prior animal pharm Chicken Soup, Bone Marrow, and EPCs for organ regeneration]

Complex Chronic Diseases and ACE/AII Activity

Diseases since the DAWN OF TIME typically involve stress (physical, mental), trauma, infection, hormone imbalances, omega-3/omega-6 imbalances and elevated insulin, are associated with elevated ACE and AII activity. ACE is a membrane-bound peptidyl dipeptidase known to act on a variety of protein substrates in the extracellular space. Known functions are the formation of angiotensin II and the degradation of bradykinin. ACE has an indispensable role in animal physiology: aids in maintaining homeostasis and preventing death during duress activated by mammalian 'fight or flight', our hard-wired mechanism for survival. A sharp cascade of neuroendocrine and circulatory chemicals are released in stressful/imbalanced situations, as the body is trying to keep blood flow to the brain, heart and vital organs, heart pumping activity and other vital processes (see below diagram). ACE catalyzes the conversion from (less active) Angiotensin I to (more active) Angiotensin II. Do we require ACE and Angiotensin II? Of course, this system required to clear damaged tissue, maintain perfusion of tissues and organs and activate the immune system for healing after trauma and infection. Tourgeman discusses the role of Angiotension II here: ' (a) increases pressure within the kidneys, (b) increases fibrosis (scarring), (c) increases the recruitment of pro-inflammatory white blood cells, (d), increases the production of inflammatory cytokines (chemicals), and (e) increases cell proliferation.'

Controlling Insulin, ACE and AII

Epinephrine (adrenaline), norepinephrine, cortisol, renin, aldosterone and other adrenal gland secretions are prompted acutely on a short-term basis. Under high insulin and chronic conditions, these powerful adrenal hormones and chemicals are inappropriately turned on long-term.

Any studies?

Frassetto et al (EJCN, 2009) showed that pre-hypertension normalized after 10 days on a hunter-gather paleolithic diet (grain-free, legume-free) in overweight men and women aged 18+ yo. This study was superby in reducing HOMA, insulin resistance, and basal insulin secretion by ~70%.

Subsequently, the systolic blood pressure reduced by 2.6 mmgHg (NS) diastolic blood pressure dropped from 71 by 3.1 mmHg (p=0.006); this is of huge magnitudes greater than those produced in the VAST MAJORITY of clinical anti-hypertensive drugs.

In younger patients the diastolic BP is more difficult to modify and lower; flips as we get older and arteries stiffen up.

A broad Cochrane review found "We found 92 trials that randomly assigned participants to take either an ACE inhibitor or an inert substance (placebo). These trials evaluated the blood pressure lowering ability of 14 different ACE inhibitors in 12 954 participants. The trials followed participants for approximately 6 weeks (though people are typically expected to take anti-hypertension drugs for the rest of their lives). The blood pressure lowering effect was modest. There was an 8-point reduction in the upper number that signifies the systolic pressure and a 5-point reduction in the lower number that signifies the diastolic pressure."

Again in the hunter-gatherer paleolithic diet (granted they were not yet hypertensive, but on the road there), IN ONLY DAYS of diet modification achieved statistically significant blood pressure reduction.

On this evolutionary/paleo diet, treatment participants consumed eggs, M-E-A-T, or seafood at EVERY MEAL.




And frequently and highly observed in individuals who lower their insulin levels and adopt an anti-inflammatory evo/paleo diet (and if necessary take antioxidants like omega-3, zinc, magnesium, etc).

Pharmaceuticals Do Not Work

IMHO ACE-inhibitor and ARB pharmaceuticals hardly at all or only marginally improve chronic disease processes. Unlike food components, drugs are strong. Artificial substances foreign to mammalian systems (xenobiotics) are not metabolized and eliminated in the same fashion as food components thereby potently binding and staying around quite a long duration. Besides binding one single receptor, they may inevitably activate or inhibit a vast variety of other interrelated receptor/enzyme systems. That is how we are built. Everything is INTERRELATED. Approximately 17% of users of an ACE-inhibitor report a dry, non-productive cough as a result of bradykinins building up which cause inflammation in the lungs, consequently resulting in an asthma-related cough. Captopril is the least because it does not affect bradykinin expression as much.

Dry, high-bradykinin, annoying, lingering, inflammation-related cough in affected ACE-inhibitor drug-users? Good? Probably not despite purported 'benefits'.

Another adverse effect of ACE-inhibitors (and ARBs) is hypotension (low BP), kidney failure and elevated potassium. These drugs, like all drugs, can cause what they are purported to 'protect'...

Blocking the final angiotensin at the receptor level is not good either. Recently angiotensin II receptor blockers (ARBs) are associated with a 20% relative increase in new cancer occurrence (7.2% v. 6.0%) compared with placebo in clinical trials (Sipahi et al, Lancet Oncology 2010). Lung cancer was the highest reported solid organ cancer incidence.

Food? Side effects? Generally not unless a food allergy exists to other food components or it promotes excessive insulin or blood glucoses or n-6/n-3 imbalances (e.g. starches, fruit, industrial farmed high n-6 meat/seafood).

Other Beneficial Foods Functioning as ACE-Inhibitors

Nutrigenomics is a new field that helps align our DNA expression to optimizing health via food, food components, and nutraceuticals (omega-3 fish oil supplements, vitamin D supplements, K2 supplements, magnesium, zinc, trace minerals, digestive enzymes, probiotics, etc). I discussed earlier: Nutrigenomics and Hypertension. The below list is adapted (I removed gluten #19).

Note: many of these are shore-based foods with high minerals (iodine, zinc, magnesium, selenium, manganese, chromium, etc).
1. Garlic
2. Seaweed
3. Tuna protein/muscle
4. Sardine protein/muscle (Anchovies too: Caeasar dressing)
5. Hawthorne berry
6. Bonito flakes (fish protein)
7. Pycnogenol (historical used flavonoid used as tea from pine bark)
8. Casein
9. Hydrolyzed Whey protein
10. Sour milk (fermented dairy)
11. Gelatin (protein)
12. Sake (fermented rice wine)
13. Omega-3 essential fatty acids -- even epigenetically reverses hypertension in bred rats
14. Chicken Egg Yolks
15. Zein (lysine and tryptophan-free protein from maize)
16. Dried Salted Fish
17. Fish sauce (fermented product)
18. Zinc
19. Rice bran (fatty acids, proteins)
20. Fermented cheeses
21. Tubers: potatoes, tumeric/curcumin, Japanese yams, Chinese yams,
22. Lactoferrin (human breastmilk, cow/goat/sheep dairy)
23. Cocoa storage protein
24. Pork protein/muscle
25. Chicken protein/muscle
26. Beef protein/muscle

Omega-3 Reverses Damage from Stressors (Insulin, Salt, Fructose, Cold Storage) and Epigenetically in Low-Protein-Mother and Stressed-Mother Rats

Omega-3 fish oil is just amazing stuff; it reduces ACE by more than one mechanism of action... It reverses all kinds of damage in rat studies and human studies caused by the S.A.D. and neolithic living. Unfortunately for the great majority of human trials, the research doses are often so low to be clinically inconsequential and inconclusive. For accurate results, I believe the dose needs to be calculated per person and based on (1) omega-3 deficiency and (2) accumulated omega-6 incorporation into cell membranes and adipose/fat stores. Current ratios in the U.S. of n-6/n-3 in blood or tissue membranes is 30:1 to (!!) 40+:1 and getting worse as we speak as many outspoken physicians, cardiologists and government agencies are trying to promote more high omega-6 canola oil and other oxidized refined vegetable oils to replace saturated fats.

Dietary n-3 PUFAs affect the blood pressure rise and cardiac impairments in a hyperinsulinemia rat model in vivo.
Rousseau D, Héliès-Toussaint C, Moreau D, Raederstorff D, Grynberg A.
Am J Physiol Heart Circ Physiol. 2003 Sep;285(3):H1294-302.

Interrelationships between salt and fish oil in stroke-prone spontaneously hypertensive rat.
Vaskonen T, Laakso J, Mervaala E, Sievi E, Karppanen H.
Blood Press. 1996 May;5(3):178-89.

Long-chain (n-3) polyunsaturated fatty acids prevent metabolic and vascular disorders in fructose-fed rats.
Robbez Masson V, Lucas A, Gueugneau AM, Macaire JP, Paul JL, Grynberg A, Rousseau D.
J Nutr. 2008 Oct;138(10):1915-22.

Beneficial effects of omega-3 fatty acid treatment on the recovery of cardiac function after cold storage of hyperlipidemic rats.
Ku K, Oku H, Kaneda T, Onoe M, Zhang Z.
Metabolism. 1999 Oct;48(10):1203-9.

Epigenetic implications:
Adult cardiorenal benefits from postnatal fish oil supplement in rat offspring of low-protein pregnancies.
Catta-Preta M, Oliveira DA, Mandarim-de-Lacerda CA, Aguila MB.
Life Sci. 2006 Dec 23;80(3):219-29.

Maternal fish oil supplementation benefits programmed offspring from rat dams fed low-protein diet.
Gregório BM, Souza-Mello V, Mandarim-de-Lacerda CA, Aguila MB.
Am J Obstet Gynecol. 2008 Jul;199(1):82.e1-7.

Developmental programming of renal glucocorticoid sensitivity and the renin-angiotensin system. [high omega-3 diet ameliorates high BP and high ACE activity in F1 generation born from rats given maternal-dexamethasone-dosing]
Wyrwoll CS, Mark PJ, Waddell BJ.
Hypertension. 2007 Sep;50(3):579-84. Free PDF.

The maternal diet during pregnancy programs altered expression of the glucocorticoid receptor and type 2 11beta-hydroxysteroid dehydrogenase: potential molecular mechanisms underlying the programming of hypertension in utero.
Bertram C, Trowern AR, Copin N, Jackson AA, Whorwood CB.
Endocrinology. 2001 Jul;142(7):2841-53.

Human study:
Fish oil [1.8 g EPA+DHA] prevents the adrenal activation elicited by mental stress in healthy [lean, young] men.
Delarue J, Matzinger O, Binnert C, Schneiter P, Chioléro R, Tappy L.
Diabetes Metab. 2003 Jun;29(3):289-95. Free PDF.

Friday, July 9, 2010

Slaying of a Hypothesis

"The great tragedy of Science – the slaying of a beautiful hypothesis by an ugly fact.“

Thomas H. Huxley (1825 – 1895)

Biologist and father of Aldous Huxley, one of my favorite authors

Critical analyses by ridiculously spectacular science writer and RawFood SOS blogger Denise Minger have illuminated the ugly facts hidden by Colin Campbell's lies and ignorance for science and statistics.

Why can't p-e-o-p-l-e critically think...? COGNITIVE FAILURES when they don't...

I cannot tell you how many ex-vegetarians tried to shovel the Campbell cr*p toward me... *cough cough* who will remain nameless.

I am Chinese and I will tell you 60% of the Chinese I know over the age of 60 yo have Metabolic Syndrome whether they live rurally or in urban areas. Same stats as the U.S.

Chris H. as ALWAYS summarizes excellently...


Asclepius highlights exceptionally well what I would consider one of the most important findings on the benefits of a high saturated fat diet in the Tuoli province HERE by an earlier blogger Brad Marshall in a 2005 blog entry, 'In China, the main predictor of heart disease rates in a given population is how much wheat flour (and other grains except rice) that population eats. The consumption of vegetables or animal products doesn't play an obvious role in heart disease rates. Tuoli county, where they eat far more saturated fat than in the US, had far less heart attack deaths than the US and no more heart attack deaths than you would suspect based on the amount of wheat they consume compared to their Chinese Colleagues.'

Prior series, Benefits of a High Saturated (MEAT-BASED) Fat Diet:

Part I: Dr. Krauss -- Pattern 'A' Achieved By 46% High 18% Saturated Fat v. Low 6% Sat Fat

Part II: Ashkanazi Jewish Centenarians, CETP and a High Schmaltz Diet

Part III: My High Sat Fat Paleo Peeps with High HDLs [with Regression or ZERO CAC EBCT SCORE]

Part IV: Regression Only in High Sat Fat Heart Female Patients

Part V: Traditional HIGH Lard-n-PORK-Consuming Okinawans

Hans v. Luke (v. Princess Leia)

Evolutionary psychology appears to be bigger than evolutionary medicine at this time...! Here is a post entry from their wonderful group, including Prof Steven Pletak -- crossfit gym owner and blogger who advocates evolutionary nutrition and fitness. The group also have an open access, peer-reviewed journal EvoS Journal: The Journal of the Evolutionary Studies Consortium.

Luke Skywalker, Han Solo, and the Importance of Adaptation Implementation in Evolutionary Psychology
By Professor Glenn Geher at EvoStudies blog (see blogroll, side)

I’m not going to lie. If you follow my work at all, hopefully this isn’t a surprise – I try to stay honest – it’s a way to compensate for my deficits. Lots of folks I know – several of whom I consider good friends – report that they just can’t stand evolutionary psychology. Some seem to think it’s the devil – morally and scientifically irresponsible and reprehensible. I do my best to deal with things, but every now and then, honestly, I just shake my head. And sometimes I just have to write about it.

A few weeks ago, a really interesting discussion about the mating-relevant differences between Luke Skywalker and Han Solo emerged in my graduate course in social psychology. This was one of these moments when a thread of the fabric of American culture and the content of the course interfaced perfectly. Luke is prototyipically non-masculine – whiny and wimpy throughout three episodes. Han is just macho. He plays it cool, doesn’t need anyone’s help, and has classic masculine good looks.

What’s attractive about Luke? What’s attractive about Han? The conversation touched on several themes relevant to evolutionary psychology – mate choice, optimal features of long-term mates, optimal features of short-term mates, morphological features of sexually attractive males, the handicap principle applied to high levels of testosterone, inbreeding depression, and so forth. It was an exciting class discussion that put a face to many of the concepts from the readings of the week.
[Read more deep thoughts here]

From the journal, I love the thoughts on mitochondria which do nutrient and energy sensing... much like PPAR nutrient and energy sensing HERE:

Blackstone, N. W. (2009). Is evolutionary theory central to molecular cell biology? EvoS Journal: The Journal of the Evolutionary Studies Consortium, 1(1), 34-43.

'Mitochondrial signaling pathways may remain as vestiges
of ancient levels-of-selection conflicts... Because mitochondria were evolutionary units capable of heritable variation, levels-of-selection synergies and antagonisms no doubt ruled the emerging features of the eukaryotic cell... Electron transport chains are typically the locus of not just energy conversion, but environmental sensing as well... Mitochondria are descended from bacteria not unlike E. coli. Primitively, they are expected to have employed similar environmental sensing mechanisms.' (see electron transport chain, below)

Other references:
Redox control in development and evolution: evidence from colonial hydroids
Blackstone NW.
J Exp Biol. 1999 Dec;202 Pt 24:3541-53.

Redox control and the evolution of multicellularity.
Blackstone NW.
Bioessays. 2000 Oct;22(10):947-53. Review.

Mitochondria as integrators of information in an early-evolving animal: insights from a triterpenoid metabolite.
Blackstone NW, Kelly MM, Haridas V, Gutterman JU.
Proc Biol Sci. 2005 Mar 7;272(1562):527-31.

Multicellular redox regulation in an early-evolving animal treated with glutathione.
Doolen JF, Geddes GC, Blackstone NW.
Physiol Biochem Zool. 2007 May-Jun;80(3):317-25.

Wednesday, July 7, 2010

Plants Produce Carbs From Air: Calvin Cycle

Homology Across 3 Phyla: Bacteria, Plants and Animals

Across 3 phyla, great homology (>90%) in our enzyme pathyways exist. The domains for energy production, synthesis and coordination are shared. See prior post: Animal Amour and Metabolic Networks

--Carbohydrate metabolism
--Energy metabolism
--Amino Acid metabolism
--Nucleotide metabolism
--Lipid metabolism

Plant Energy Conversion: Calvin Cycle

Plants produce energy for higher life forms to consume and spread seed. Flowering plants are only a recent blimp in the evolutionary timeline. Seeds in high-carbohydrate-containing fruit co-evolved with multi-cellular animals it appears.

From air (CO2) and light (sun UV energy) carbohydrates, fatty acids and proteins are biochemically produced. Magic?



Plant Bio 101: Fructose, Glucose, Sucrose Produced from Calvin Cycle

How the Calvin Cycle Works Animation + Quiz (click)

Light is absolutely required. The Calvin Cycle cannot occur without UV energy, sunlight.

Fructose (monosaccharide) is first produced then interconverted to glucose (monosaccharide) with a one-carbon change, then sucrose is fused which can be transported throughout the plant. Sucrose (disaccharide) is fructose + glucose linked. Starch is complex carbohydrates linked together; digestion is the process of breaking down starch by our salivary amylases (enzymes = 'cutters'), our pancreatic enzymes and gut flora into glucose. Diagram courtesy of plant physiology Prof Ross Koning.

Table sugar = sucrose = fructose+glucose
Lactulose = galactose+fructose (see Dr. Ayers post)
Lactose = galactose+glucose (dairy)
Maltose = glucose+glucose

Starch = complex carbohydrate
High-Fructose-Corn-Syrup (HFCS) = fructose + contaminants (pesticides, GMO corn residues, LEAD)

Glucose is a 6-carbon chain Derivatized to Carbs, Protein, Fatty Acids

Outside of the Calvin Cycle, glucose can be made into other molecules for use into starches, cellulose, protein and fatty acids. Glucose is flexible. It can be made into so many useful things.

Plant products are ubiquitous and humans have figured out ingenious ways to use them for centuries outside of food and shelter:
--food (fruit, fats, lignans, roots/tubers, stems, leaves, etc)
--fatty acids (oils, biodiesel, fragrances)
--medicines (antioxidants, vitamins, herbals, rejuvenants, chemotx)
--musical instruments (wooden flutes, guitars, violins)
--clothing (cotton, hemp, etc)
--compost (nitrogen renewal, etc)

Plants -- Calvin Cycle; Animals -- GNG + Fat Burning

From single carbons from carbon dioxide (air) and light, plants can produce a 6-carbon ring known as glucose for energy and storage of energy (starch, fatty acids, protein) via photosynthesis and a special energy pathway known as the Calvin Cycle. ATP is used up in the process and light energy is absolutely mandatory.

On the other hand, animals have an advantage with the evolution of an analogous special energy pathway for glucose production, known as gluconeogenesis (GNG), without requiring sunlight. Unlike plants, animals do not require sunlight for production of energy and glucose, and therefore the advantage of more mobility and movement.

Mitochondria are absent in all lifeforms except the eukaryotic branch. Bacteria (prokaryotes) ARE mitochondria *haa*. Plants and animals hijacked their technology...aka, endosymbiosis...

Fat energy release provides almost four-times more energy per molecule. On a carbon-per-carbon basis, 33% more energy is produced (when I compare Stearate 18:0 and Glucose 6-carbon by pure stoichiometry, which is wrong but oh well).

Carbs. Glucose is equivalent to only ~1 tsp (5 grams) in our blood. Glycogen is stored ~100-200 grams in muscles and ~400-500 grams in the liver. Less than one kilo of carbs is stored and running through our veins.

Fat. For 10-20% body fat (composition like most omnivores or carnivores), an average human carries 5 to 10 kilos of fat.

Super powered fuel may be utilized anytime for energy conversion whenever we are in the fat-burning mode.

By harnessing fatty acids for energy, in many ways this propelled organisms with mitochondria to the top of the food chain. Read more about mitochondria in Nick Lane's Power, Sex, Suicide and prior posts HERE.

The birth of PHAT hominid babies with enormous stores of super powered fatty acids produced the evolution of walking, hairless, bigger-brained hominids to the top-tiered creatures that we supposedly are now. Read Stephan Cunnane's Survival of the Fattest and prior posts HERE and HERE.

See prior post: Aerobic Glycolysis (~38 ATP; 6-carbon) v. Aerobic Fat Beta-Oxidation (~146 ATP; 18-carbon)

Courtesy N Engl J Med 2007;356:1140-51.

Mitochondria: Fat Burning Powerhouses + Source of All Chronic Diseases

Without mitochondria derived from bacterial origins of 3.8 billion years ago, animals would not have the ability to efficiently burn the most powerful energy source, fatty acids, and become the most successful predators on the planet.

Not only are mitochondria the nuclear powerhouse of energy, that produce ATP from powerful fats, they are also believed by many who study evolutionary medicine to be the source of all chronic ailments and conditions. Glucose energy is cheap fuel and kills mitochondria when excessive. Many drugs are mitochondrial poisons (e.g. statins). By affecting the thermostat of energy controllers (ratios of NAD/NADP and ADP/ATP) the imbalance affects SIRT-1, AMPK, PPAR and mTOR in a variety of tissues. Depending on the organ, these are known as chronic conditions -- autoimmunity disorders, heart failure, hypertension, adiposity, infertility, cancer, diabetes, et cetera.

Control Insulin, Control Cancer and Chronic Diseases

Benefits/Risks of Insulin

Controlling insulin reaps many rewards. As the previous article suggests, insulin is an ancient hormone ubiquitous in all animals -- from worms to humans -- with classic/nonclassic responsibilities including (see Table 1). Some of these actions are beneficial like thermogenesis, however many of the others are detrimental in the great majority of situations:
--low potassium
--raised heart rate
--increased uric acid (ie, gout
--increased clotting
--CNS stimulation (ie, anxiety, epression, ADHD)
--prevention of fat from being liberalized for energetic uses

We require only tiny, neglible amounts of insulin for thermogenesis and shuttling of energy (glucose) into muscles and liver for storage.

Damage from Insulin Resistance

In fact, increased energy expenditure is exponentially increased when insulin resistance is kept at bay. What is insulin resistance (IR)? It is like being at a rock concert (or Hannah Montana venue with screaming little girls everywhere) where temporary hearing loss is induced by inclement noise pollution. As soon as the volume returns to a low level, hearing resumes. Shut insulin down by going grain-free, carb-restricted, intermittent fasting and exercising, then inflammatory responses and processes are cut off. The same research demonstrated that men and women have blunted energy expenditure when the 'volume of insulin' is dialed exceptionally high. And for us women, we may even have a 'negative' energy output (in other words 'storage') with energy expenditure during the presence of insulin resistance... Insulin-resistant gals may gain weight with exercise lower rates of energy expenditure... This actually is a common phenomenon and very discouraging for women trying to lose weight and fight an uphill battle as they eat per conventional medical advice 'low fat'/high-carbohydrate/insulin-inducing diets (USDA 'whole grain' pyramidal nonsense).

How To Reduce Insulin Resistance

Degrees of IR can also be effectively cranked down by (Isharwal S, et al. Dietary nutrients and insulin resistance in urban Asian Indian adolescents and young adults.Ann Nutr Metab. 2008;52(2):145-51.):
--normal BMI achievement
--reduction of pro-inflammatory omega-6 oils (nuts, beans, oils from corn soy peanut sunflower)
--increase of anti-inflammatory omega-3 EPA+DHA oils (ie, cod liver, fish oil, pasture-fed milk, meat, eggs, etc)

And of course...wheat avoidance, grain elimination, carb restriction, intermittent fasting and exercise.

Excessive insulin (ie, hyperinsulinemia) leads to the below changes (see below diagram):
--generation of TGs and small dense atherogenic LDL
--conversion from fatty streaks to plaque
--plaque growth
--increased adipose tissue mass (Obesity, Metablic Syndrome, PCOS)
--accumulation of Triglycerides in non-adipocytes
--nonalcoholic steatohepatitis (fatty liver/NAFLD)
--pancreatic beta-cell failure (fatty pancreas, insulin resistance)
--dilated cardiomyopathy (myocyte (heart cell) stiffening and diastolic dysfunction)
--arterial stiffening
--blood glucose spikes
--expansion of visceral fat (belly fat colonies)
--fatty liver, fatty pancreas, fatty gallbladder, fatty heart (lipotoxicity)
--Diabetes Type 2
--strokes, heart attacks
--cancer (see end)

Lipotoxicity from Excessive Grains and Carbohydrates

Whole human systemic organ functions may become dominated by hyperinsulinemia, leading to all sorts of dysfunction and energy dysregulation. Why rely on primitive petrol... when nuclear power exists? Mitochondria are the powerhouses of ATP, nuclear energy. Excessive carbohydrates shut mitochondria off... and lead to lipotoxicity.

Fig 1. Lipotoxicity in humans originates from excessive release of free fatty acids from hypertrophied adipocytes in obese persons. Organ exposure to high levels of free fatty acids causes lipid droplets to accumulate within the cytosol of nonadipose tissues in proximity to mitochondria (white arrows, bottom).By-products of cytosolic triglyceride accumulation and of lipid metabolism may lead to organ dysfunction and failure. McGavock JM, Victor RG, Unger RH, Szczepaniak LS. Adiposity of the heart, revisited. (Full PDF here.) Ann Intern Med. 2006 Apr 4;144(7):517-24. Review. PMID: 16585666

The inflammation associated with insulin is akin to the oxidative damage that occurs when soft materials like rubber or plastic is left outside exposed to the elements. Over time, the rubber hardens and becomes inelastic and rigid, easily breaking with any shear force. Sort of like running a high-powered hose made out of glass, right? With the elimination of inflammatory influences, human tissues can return to their original soft, elastic, pliable states. This includes endothelium, heart blood vessels, contractile tissues like our heart and skeletal muscles... even our oral gum tissues.

Reversal occurs when insulin is shut down.

The previous review of the research eloquently illustrates the special properties that dictate this ancient 'reactive' hormone. Insulin is one of the few hormones that is controlled by consumed 'substrates'.... What is in charge of turning insulin on and off? What are substrates of insulin?


Food composition directly lowers or raises insulin concentrations. Various other factors of course determine how quick and how sustained hyperinsulinemia occurs (exercise, weight loss, skeletal muscle dominance, size and location of visceral fat colonies (ie, 'belly' is 'bad') but in essence our food controls blood insulin levels.

If what we put in our mouth dictates are insulin levels, then equally powerful is what we don't... In other words, processes like starvation, skipping meals, random eating, intermittent fasting and going low-carb or restricted-carb are ways to reduce and control insulin. Consumption of adequate protein and fats and fiber control insulin release as well.

Consider the complete avoidance of all wheat and grains:
--wheat products (incl cereal, pasta, noodles, bread, crackers, pita, tortilla)
--bulgur (cracked wheat)
--oat (except oat bran)
--corn (incl popcorn, grits, cornmeal, tortilla, chips)
--et cetera

Consume most of the carbohydrates from non-starchy vegetables and raw nuts/seeds and low-GI fruit like berries.

Cancer and the Carbohydrate and Insulin Connection

Controlling insulin not only controls CAD but also controls cancer... Is 'whole grains' just promoting 'whole C-A-N-C-E-R'? As well as 'whole CORONARY ARTERY DISEASE'?
--breast cancer
--prostate cancer
--colon cancer
--pancreatic cancer
--brain cancer
--gallbladder cancer
--kidney cancer
--thyroid cancer

Cancer and Carbs/Insulin References
  • Berstein LM. Endocrinology of the wild and mutant BRCA1 gene and types of hormonal carcinogenesis. Future Oncol. 2008 Feb;4(1):23-39. Review. PMID: 18240998
  • Hede K.Doctors seek to prevent breast cancer recurrence by lowering insulin levels.
    J Natl Cancer Inst. 2008 Apr 16;100(8):530-2. PMID: 18398091
  • Barnard RJ.Prostate cancer prevention by nutritional means to alleviate metabolic syndrome. Am J Clin Nutr. 2007 Sep;86(3):s889-93. Review.PMID: 18265484
  • Park JH.Inhibition of colon cancer cell growth by dietary components: role of the insulin-like growth factor (IGF) system. Asia Pac J Clin Nutr. 2008;17 Suppl 1:257-60. PMID: 18296350>
  • Tenenbaum A, et
    al. Does the lipid-lowering peroxisome proliferator-activated receptors ligand bezafibrate prevent colon cancer in patients with coronary artery disease? Cardiovasc Diabetol. 2008 Jun 19;7(1):18. PMID: 18565233

  • Pisani P. Arch Physiol Biochem. 2008 Feb;114(1):63-70. Hyper-insulinaemia and cancer, meta-analyses of epidemiological studies.

    Background: A substantial body of evidence links sex hormones, diet, excess body weight and physical activity to the risk of developing cancer at several sites common in affluent countries. The hypothesis that high circulating levels of insulin could be the underlying factor increasing cancer risk has been proposed. Epidemiological studies on markers of hyper-insulinaemia and cancer are reviewed and summarized.
    Methods: Studies of cancers of the colon and rectum, pancreas, breast, and endometrium examining the association with blood levels of C-peptide, insulin, glucose, glycated haemoblobin (HbA1c) were searched in PubMed. Multivariate, adjusted relative risks (RR) and their 95% confidence intervals were abstracted and summarized by meta-analyses.
    Results: Most of the studies identified were cohorts that relied on measurements obtained at baseline or assessed in blood stored at low temperature several years before the onset of cancer. The meta-analyses showed excess risks of colorectal and pancreatic cancers associated with higher levels of circulating C-peptide/insulin and with markers of glycaemia. Significant heterogeneity was found among four epidemiological studies of endometrial cancer and C-peptide giving a summary RR compatible with no association. Overall breast cancer risk was significantly higher in the upper categories of C-peptide/insulin, however, the excess derived entirely from retrospective studies.

    Conclusion: Current evidence suggests that subjects who develop colorectal and pancreatic cancers have increased pre-diagnostic blood levels of insulin and glucose. PMID: 18465360

This is post is a reprise from two years ago... sadly holds true more than ever.

Evolutionary Medicine post:
Metformin, Insulin Resistance and Cancer

Monday, July 5, 2010

Animal Amour and Metabolic Networks

Les Nubians: Amour à Mort [Love Unto Death]
Courtesy Youtube.com


We're dogsitting this weekend, K, a 3-year old blond lab who has the most warm beautiful hazel eyes. My second daughter calls them 'copper hazelnut' eyes. She loves bossing him around... *haaa* Being the youngest, she finally has someone. He's a darling, patient and immensely playful.

My Animal Farm Growing Up

I grew up around animals but I look at them with different eyes knowing some science now. We lost our 12-14 year old 3 cats over the last 4 years to thyroid conditions -- 2 had Grave's and one had diabetes (and I think undiagnosed hypothyroidism). As a kid in Pennsylvania, we raised 2 rabbits and 3 turtles. My parents who grew up around pigs and animals for consumption really did not take to the idea of pets but we still had pets. After moving to Sacramento in 1979 my parents bought a farmhouse off of Florin Road which had geese, ducks, horse stable, rabbits and pigeons. We brought back 2 rabbits and 4 pigeons to our suburban home and raised them along with our 2 hamsters, 2 fox terriers Phillip and Fluffy, Tiger our red Irish setter, and a fresh-water aquarium. On and off we had 'pet' earth worms, praying mantis, dragon flies. tadpoles/frogs and other assorted backyard creatures. *haa* Pure happy mayhem may have been a good descriptor. Well we grew older, busy with school and tennis and had to find new homes for our furry, feathery and scaled friends.


Taking K hiking through the wooded Sunol park today I forget how animalistic animals are. Yes we had feline pets before but they were entirely domesticated except for the birds or cute mice they'd bring back for us for show. Actually 2 of our 3 cats were good hunters and brought back quite a few kills. Lynx would attack dogs and when one dog-owner approached us to note that Lynx must be sick because he stopped attacking her dog. We took him to the vet afterwards to learn he had Grave's hyperthyroidism.

Our temporarily adopted dog K tried to mark/impart his SCENT on every snag of vegetation, garbage can and tree during our hiking excursion. How can dogs urinate all day long?? Is it just 1-2 Tbs at a time?? He apparently was not interested in any of the raccoon or horse scat, but only other canine remains. Is it so hard-wired to be aware of other canines in the vicinity? What purpose? Territorial and reproductive instincts alone??

Most feline and canine eat only once a day. They are quite suited to intermittently fast routinely. Humans, are we so different? I don't think so.

Cunnane and Domesticated Fox

Cunnane writes in his epic book 'Survival of the Fattest' an interesting anecdote about the adrenal glands of a line of fox which are domesticated. He notes that the size of the adrenals shrink with domestication. Perhaps the constant necessity for testosterone, cortisol, progesterone and estrogen are no longer mandatory when food and survival are not ubiquitious requirements?

Is this what happened to humans with the advent of agriculture and animal husbandry?

Animal Husbandry?

WTF. Why such a name??? *haaa*

Human's Best Friend

Khyber is a great jogging partner. I took him on a couple trail hike/runs at Sunol and he did wonderfully -- matching my pace despite an annoying leash to his harness, leading me while not smelling every f*cking mark left from previous dogs, and somewhat providing protection. If a rattlesnake or mountain lion intersected our path, I do believe Khyber would have kicked into predator mode without a doubt and kicked some *ss. When we were in Mt. Shasta last week, we came upon rattlesnakes not only directly on our horse ride through the hills (to a SECRET cave *FUN!!!*) but also when we went to the waterside, we were cautioned that a young rattlesnake was found the night very close to the camps. Apparently it is unusual for rattles this time of year and the region -- the rain and recent change in weather plays a part apparently.

Metabolic Networks

When we were in Shanghai earlier this year, we met up with researchers who do research on Metabolic Networks which requires a strong background in physics, genomics, evolutionary biology, systems biology, bioinformatics, mathematics, biochemistry and a variety of other disciplines.

[Thank you LePine for your insights]

What I realize that is that we share so much homology with all living organisms, and this may go back to the first archebacteria 4 BILLION years ago (bya). Our mitochondria are the remnants of bacteria that have been push forwarded into mammalian cells. We can track the DNA signatures of the first life forms on earth to our mitochondria DNA which comprise of a humble set of 37 genes. Without mitochondria for energy systems, we would not have evolved.

Homology v. Complexity of Higher Life Forms

I think this diagram says it all (it actually crashed my computer twice). See citation #6. Homology exists between all life forms. Complexity however increases with increased skills of predation, IMHO. Humans are apparently at the apex of predation -- have taken over the earth and colonized every imaginable niche. (sometimes I think the bacteria have us by the GUT, pun intended *HAA*) Unfortunately our life form is also damaging earth in every imaginable niche as well -- terrestial, aquatic, and atmospheric...

'Red' Hotspots for Conservation of Individual Metabolic Pathways Between Archebacteria and all other Life Forms: Carb, Energy, Amino Acid, Nucleotide, and Lipid Metabolism

The 'red' color indicates greater than 90% of enzymes with significant DNA and protein sequence similarity. To appreciate our evolutionary past to 4 billion years ago, it is hard to escape our bacterial foundations that interact with our biology on every level: our metabolism, our gut, our pathogens, our immunity.

Longevity and Curing Cancer, Chronic Conditions and CAD

I would consider myself a strategist for conceiving longevity... I didn't plan it this way but by ameliorating a chronic condition with either pharmaceuticals or diet/lifestyle means, we are trying to improve longevity.

Mitochondria hold the the key between the balance between mTOR, SIRT-1, AMPK, and PPAR, as we've discussed before. These mini nuclear powerplants of energy production represent the link from our primordial past to the neolithic new world.

We are only as strong as our weakest mitochrondria...

Prior posts (Dr. Tourgeman, Dr. BG):

SIRT-1 -- (1) SIRT-1 (2) Aging and SIRT-1 (3) Evolutionary Skin and Muscles


1. Unusual pathways and enzymes of central carbohydrate metabolism in Archaea.
Siebers B, Schönheit P.
Curr Opin Microbiol. 2005 Dec;8(6):695-705. Epub 2005 Oct 26. Review.

2. Evolutionary aspects of whole-genome biology.
Doolittle RF.
Curr Opin Struct Biol. 2005 Jun;15(3):248-53. Review.

3. Distribution and phylogenies of enzymes of the Embden-Meyerhof-Parnas pathway from archaea and hyperthermophilic bacteria support a gluconeogenic origin of metabolism.
Ronimus RS, Morgan HW.

4. The unique features of glycolytic pathways in Archaea.
Verhees CH, Kengen SW, Tuininga JE, Schut GJ, Adams MW, De Vos WM, Van Der Oost J.
Biochem J. 2003 Oct 15;375(Pt 2):231-46.

5. Microbial behavior in a heterogeneous world.
Fenchel T.
Science. 2002 May 10;296(5570):1068-71. Review.

6. The conservation and evolutionary modularity of metabolism.
Peregrín-Alvarez JM, Sanford C, Parkinson J.
Genome Biol. 2009;10(6):R63. [Free PDF here.]

Friday, July 2, 2010

Celeb*tchy grrls know their vitamin D and Osteoporosis

Celeb*tchy (ok... where I lurk for laughs...): Gwyneth Paltrow has vitamin D deficiency may develop osteoporosis

Gwen, get some:

1. vitamin D 5000 IU daily in the morning
2. sunshine sans sunscreen
3. vitamin K2 100mcg daily (and/or fermented foods, dairy, CLO)
4. Magnesium (citrate, malate, taurate (since you don't eat much MEAT), chelate, etc) 500-1000mg daily or more
5. BONE BROTH w/grassfed bones + REAL FOOD + FAT D*MN IT
6. Worried, melanoma? Don't. Consume real food/antioxidants proven to prevent UV damage (selenium, iodine, NAC (glutathione presursor), vitamin C + natural E tocopherol, proanthocyanidins (wine/grape seed), pycnogenol, thyroid, maca, plant/animal polyphenols, etc)
7. repeat bone mineral density (BMD) in 2-3 yrs -- will be improved...?normal probably
8. avoid bisphosphonates which make a brittle bone matrix, not crosslinked correctly (like an unstable dense house on sand) -- which are drugs highly linked to spontaneous fractures, poor gum/bone healing, jaw osteonecrosis, inflammation and atrial fibrillation (=strokes/mortality/lifelong-warfarin/etc)
9. lower your serum insulin (basal, postprandial)
10. minerals + hormones: pregnancy leaches minerals and bone-protective hormones (omega-3, vitamin D) vertically to the baby unless mom is totally replete. Birth control especially progestins (ALL) lower bone mineral density compared with placebo (Depo-Provera, the worse, because injected; pellets and IUD and orals, TOTALLY bone degrading)

***Comments crack me up from: cheekemunkey, MightyMouse (no it's not me, I'd be batgrrrl) *haa aha*

Sounds like evo/paleo hunter-gatherer grrrrls.

Peter initiated... *haa*

Hyperinsulinemia and Metabolic Syndrome (which is a high insulin syndrome) are highly associated with bone degradation, bone fractures and osteoporosis. Consider also a grain-free, soy-free, lower carbohydrate diet... to prevent trigging all that insulin that grows inflammatory belly fat which breaks down bone.

Osteoporosis Resources:

o The Standard, Guilliam PhD

o Vitamin D 5000 IU daily normalizes 25OHD PTH in 12 months and improves BMD as good/better than a bisphosphonate (thanxxx Neo!)

Healthy bones [and clear arteries without calcifications, see Rotterdam and HERE] require as evident in this recent study:
--25OHD ~50 ng/ml
--PTH < 20 pg/ml

--[optimal thyroid (TSH FT4 FT3 rT3) -- not discussed, important and ultimately vital for the intimately inter-related network of endocrine organs: parathyroid, thyroid, kidneys, adipose, gonads, marrow... B-O-N-E-S ]

Evolutionary Medicine posts (Dr. Tourgeman):

(1) Brain, Bone and Metabolism (2) Celiac Disease and Osteoporosis; (3) Drugs That Weaken Bone Structure

Thursday, July 1, 2010

'Woman Makers': Cry Like a Little Grrrl

Diablo CrossFit "Woman Makers"
from Diablo CrossFit on Vimeo.

Here is haaaawt Jeremy, Crossfit coach and co-owner showing how to do Woman Makers... 6min MetCon after 3-3-3-3-3-3-3 strict push presses. I love talking digestive, health and paleo topics w/him and other members. Recall his Primal Nutrition 101, upside down food triangle (sans 'lots of s*x'): HERE.

Did 28 but I lost count (30? 32??) in 6 min AMRAP (as many reps as possible). I didn't Rx either, just 20# wts (instead of 25# or 36#)