Acupuncture & Chinese Medicine ● Longevity Nutrition

Evolutionary biology

 

Chokecherries

In the temperate zones of the Earth, late summer into autumn has been a time of celebration in many cultures. This is the time when all creatures breathe a sigh of relief as the hard work of growth slows. The cooler air transforms summer’s searing rays of sunshine into loving, golden warmth. Pregnant with sugar, fruits of flowering plants hang heavy from the branches and dapple the landscape in a mosaic of reds, blues and purples from anthocyanins and carotenoids. On the ground, combinations of lutein and zeaxanthin color the winter squashes of the Cucurbita family with the same oranges and yellows that are revealed as chlorophyll relinquishes its dominion over the foliage.

Colorful pigments that once acted as a beacon for pollinators in an array of colors and hormones[1] assume a new form that will serve as this year’s bridge of survival for numerous species of birds and mammals, including humans.

Over these precious few weeks, concentrated glucose and fructose flow in like the ocean tide. With them, the stomach’s master hormones of appetite flip flop. Ghrelin’s waxing and leptin’s waning[2] impose an ever-rising voracity of appetite that has driven successful survival of species over hundreds of millions of years. Inside the sweet goodness lurks even more treasures. Fresh omega-six oils from seeds and grains give a fresh boost to dwindling eicosanoids that are crucial for cell-to-cell communication. Vitamin E, selenium[3], vitamin C and phytonutrients stand like a levy to ensure the rising tide of inflammation doesn’t breach its banks.

In Traditional Chinese Medicine Theory, this time of year was considered the fifth season associated with the Earth element.  Warmth, sunshine, water and Earth have been magically transformed by a billion tiny seeds into a form that passes life’s nourishment unto us.   In the Jewish tradition, this season beckons the new year known as Rosh Hashanah.

“Blessed are you, sovereign of the Universe who brings forth bread to the Earth…who has kept us in life, has sustained us and brought us to this season.” Torah

Lurking deep within the cell, all the way down to the nuclear membrane, a sugar-laden surge of insulin nudges a sleeping Goddess from her torpor. 2.1 billion years ago[4],[5] some of the earliest fungi birthed this goddess and time kindly bequeathed her unto humans. In science she is known as SREBP or sterol regulatory elemental binding proteins. She is the one who, as if by magic, signals that transformation of sugar into a form that can be stored for later use as triglycerides[6] and fat[7].  Without her, most animals in the temperate and arctic zones are unlikely to survive even one winter.

Because of SREBP’s, every cell can make its own LDL cholesterol for membrane repair and vitamin D synthesis. However, without a way to supply basic antioxidants to the cell, LDL quickly oxidizes. This transformation from Dr. Jeckel to Mr. Hyde damages everything it touches[8] and is considered to be one of the driving forces of atherosclerosis7. In order to protect her inner world and ensure a constant supply of antioxidants, SREBP must ask for a little help from one of her cousins in the liver, SREBP-1. While most of the cells of the body settle for glucose as an energy source, the liver engages in a more refined taste for fructose. In fact, liver cells are the only ones that can use fructose and its effects are incendiary. Fructose drives rapid production of LDL cholesterol, fats and inflammation in the liver[9],[10]. This preference for fructose acts as a supply chain for the trillions of cells’ insatiable need for antioxidants during times like these. But without SREBP, these antioxidants are useless. She alone is the key master who permits passage of these antioxidants across the cell membrane. Under the dominion of SREBP, the LDL cholesterol receptor rises to the surface of the cell like a fish rising to feed. If it is lucky, LDL cholesterol will land in its mouth. Along for the ride, precious antioxidants like vitamins A, C, and E are granted access to the cell’s inner world[11].

As this season wanes, berries hang dried and scant on the branches. Insulin recedes as the sugar festival comes to a close. The Earth cools. SREBP breathes a deep sigh as her hard work comes to an end. As she falls into her winter nap, she brings many of the creatures of the Earth with her. Only one creature has successfully escaped the dominion of this goddess. Humans innovated to store carbohydrates externally. This consistent supply of sugar drives insulin to ensure that SREBP never sleeps. Her unrelenting state of slavery drives disorders like obesity[12],[13], fatty liver[14], insulin resistance[15] and atherosclerosis[16], [17]. Perhaps this goddess would argue that these are not diseases at all but are phenotypes brought on by depriving her of a proper rest.

[1] Cutler A.J., Krochko J.E. Formation and breakdown of ABA. Trends Plant. Sci. 1999;4:472–478. doi: 10.1016/S1360-1385(99)01497-1

[2] Teff KL, Elliott, SS, Tschop M, Kieffer TJ, Rader D., Heiman M., Townsend RR., Keim NL, D’Alesso D, Havel Dietary fructose reduces circulating insulin and leptin, attenuates postprandial suppression of ghrelin, and increases triglycerides in women. PJ J Clin Endocrinol Metab. 2004 Jun;89(6):2963-72

[3] Giacomo dugo, Lara La Pera, Donatella Pollicino, marello Saitta. Determination of Selenium Content in Different Types of Seed Oils by Cathodic Stripping Potentiometry (CSP) J. Agric. Food Chem., 2003, 51 (19), pp 5598–5601

[4] Timothy F. Osborne, Peter J. Espenshade Evolutionary Conservation and Adaptation in the Mechanism that Regulates SREBP Action: What a Long Strange tRIP It’s Been. Genes & Dev. 2009. 23: 2578-2591, doi:10.1101/gad.1854309

[5] V Laudet Evolution of the Nuclear Receptor Superfamily: Early Diversification from an Ancestral Orphan Receptor. Journal of Molecular Endocrinology Dec. 1, 1997. 19 2-7-226

[6] Colleen K. Nye  Glyceroneogenesis Is the Dominant Pathway for Triglyceride Glycerol Synthesis in Vivo in the Rat The Journal of Biological Chemistry, 283, 27565-27574.  October 10, 2008

[7] Hitoshi Shimano, SREBPs: physiology and pathophysiology of the SREBP family. The FEBS Journal 2009 276:3 616-621

[8] Low Density Lipoprotein Can Cause Death of Islet β-Cells by Its Cellular Uptake and Oxidative Modification Miriam Cnop, Jean Claude Hannaert, Annick Y. Grupping, and Daniel G. Pipeleers Endocrinology 2002 143:9 , 3449-3453 http://dx.doi.org/10.1210/en.2002-220273

 

[9] Zhang C, Chen X, Zhu RM, Zhang Y, Tu T, Wang H., Zhao H, Zhao M, Ji YL, Chen YH, Meng XH, Wei W, Xu DX. “Endoplasmic reticulum stress is involved in hepatic SREBP-1c activation and lipid accumulation in fructose-fed mice.” 2012 Aug 3;212(3):229-40. doi: 10.1016/j.toxlet.2012.06.002. Epub 2012 Jun 12.

“ER stress contributes, at least in part, to hepatic SREBP-1c activation and lipid accumulation in fructose-evoked NAFLD.”

[10] Koo HY, Miyashita M, Cho BH, Nakamura MT. Replacing dietary glucose with fructose increases ChREBP activity and SREBP-1 protein in rat liver nucleus. 2009 Dec 11;390(2):285-9. doi: 10.1016/j.bbrc.2009.09.109. Epub 2009 Sep 30.

“Nuclear SREBP-1 was 2.2 times higher in fructose-fed rats than glucose-fed rats.”

[11] Maret G Traber, Herbert J Kayden “Vitamin E is Delivered to Cells via the High Affinity Receptor for Low-Density Lipoprotein” The American Journal of Clinical Nutrition 40: October 1984, pp 747-51.

[12] Hitoshi Shimano, SREBPs: physiology and pathophysiology of the SREBP family. The FEBS Journal 2009 276:3 616-621

 

[13] Hitoshi Shimano, SREBPs: physiology and pathophysiology of the SREBP family. The FEBS Journal 2009 276:3 616-621

[14] Moon YA, Liang G, Xie X, Frank-Kamenetsky M, Fitzgerald K, Koteliansky V, Brown MS, Goldstein JL, Horton JD. The Scap/SREBP pathway is essential for developing diabetic fatty liver and carbohydrate-induced hypertriglyceridemia in animals. Cell Metab. 2012 Feb 8;15(2):240-6

[15] Iichiro Shimomura, Robert E. Hammer, James A. Richardson, Shinji Ikemoto, Yuriy Bashmakov, Joseph L. Goldstein,Michael S. Brown

Insulin resistance and diabetes mellitus in transgenic mice expressing nuclear SREBP-1c in adipose tissue: model for congenital generalized lipodystrophy. Genes Dev. 1998 October 15; 12(20): 3182–3194.

[16] Karasawa T, Takahashi A, Saito R, Sekiya M, Igarashi M, Iwasaki H, Miyahara S, Koyasu S, Nakagawa Y, Ishii K, Matsuzaka T, Kobayashi K, Yahagi N, Takekoshi K, Sone H, Yatoh S, Suzuki H, Yamada N, Shimano H. Sterol regulatory element-binding protein-1 determines plasma remnant lipoproteins and accelerates atherosclerosis in low-density lipoprotein receptor-deficient mice. Arterioscler Thromb Vasc Biol. 2011 Aug;31(8):1788-95.

[17] Kurtak, K. Dietary and Nutritional Manipulation of the Nuclear Transcription Factors, PPAR’s and SREBP’s, as a Tool for Reversing the Primary Diseases of Premature Death and Aging. Rejuvenation Research 17-2. April 2014. P 140-44.

 

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This is a continuation from the previous post in which one of my readers asked about methionine restriction as it relates to longevity and methionine content in eggs.  I never claim to be “the knower of the answer” but I like to provide enough information for people to form their own, and perhaps new, ideas.

 As I mentioned last time an increase in metabolism will always result in an elevation of all ROS in cells.  This, by default, speeds cell turnover and aging.  Inversely, reduced metabolism reduces turnover and aging of cells.  This is the same mechanism through which caloric restriction is theorized to promote longevity.   

Restriction of any substance that is severe enough to slow down metabolism causes the mind and body to go into a torpor-like state.  If it doesn’t, damage is incurred.  I see this regularly in my practice as a condition that I have termed “Boulder Syndrome” which I’ve talked about in previous posts.    

It seems that in order to live longer though means of dietary restriction, you have stop fully living or suffer health consequences.  Take SAMe as an example.  SAMe is made from methionine in the liver and acts as the rate limiting step in the production of several neurotransmitters. These include dopamine, serotonin, norepinephrine and its conversion in the brain to epinephrine.  Low levels of these neurotransmitters tend to reduce mental clarity, motivation, drive and overall energy.  This is likely part of the whole conservation mechanism that would naturally slow down the body in times of protein scarcity.

Eggs are so interesting because they contain all the essential nutrients to carry out Phase 1 detoxification and methylation in the liver (choline, methionine, magnesium, B12, B6 and folate).  It happens that a deficiency of any one or more of these essential nutrients has a documented effect on reducing fertility. (Sorry, I just didn’t have time to find that many references for one statement but I can assure you it is a fact).   As I mentioned in the previous post, this could be from some type of signaling from Phase 1 that would indicate the presence of sufficient nutients available for reproduction.  I suspect that if the above nutrients are scarce, Phase 1 probably slows for the purpose of conserving them to maintain other bodily functions more consistent with survival and not reproduction.

Consider how we evolved eating eggs.  In non-tropical zones, eggs are in abundance mainly in the spring and early summer.  As the weather warms the insects hatch providing a sustainable protein source for birds.  The increase in dietary protein, and thus methionine, in birds’ diets would signal the appropriate anabolic processes for them to become fertile and produce eggs.  A few weeks later, early humans would have access to these eggs which would provide the appropriate nutrients for signaling anabolic processes to start preparing them for reproduction.  Methionine moves like a wave through the food chain, from sulfur in soil to plants to insects to birds to humans, signaling the anabolic processes that enable reproduction.

In tropical zones, eggs would have been available most of the time as would an abundance of nutrients that would support reproduction. This scenario applies more to the people of the developed world.

I don’t think simple reduction of dietary methionine intake is sufficient enough to slow aging.  I think it has to be fairly extreme.  Alternatively, I do think that excess amounts of methionine, which would imply excess amounts of protein could be damaging especially if intake of magnesium, folic acid, B12 and B6 is insufficient.  We also have to consider that if we reduce methionine enough to slow down metabolism, caloric consumption must be reduced as well or the slower metabolism will lead to weight gain.

That said, if you would still like to try to reduce your dietary methionine here are some things to consider.  With regards to dietary intake, you have to look at absorption rates. This is influenced by the ratio of methionine to the other amino acids in the protein source.  As a general rule, amino acids will compete with one another for absorption. For example, if you have low levels of threonine, high valine levels inhibit the absorption of methionine  (Anyone want to research which protein sources have these ratios? Good data at http://www.nutritiondata.com/ )  The higher the ratios of other amino acids the lower the absorption will be of methionine.  Animal proteins contain high levels of methionine but much higher ratios of the various other amino acids so ultimately methionine absorption is diminished. I checked some methionine levels in various protein sources and unfortunately got varying results.  It turns out that methionine content of food is related to sulfur content in the soil so there will be significant variability depending on the geography of the food source.  However as a general rule, cottage cheese, eggs and fish were all similar in methionine content. Pork and poultry were a bit higher.  Beef was high but had really high levels of competing amino acids.  Legumes and seeds were much lower.  NOW FOR THE INTERESTING PART.  It has been suggested that a vegan diet offers less methionine and would contribute to longevity through methionine restriction.  However, I found a study done on amino acid absorption in rats.  It turns out that pinto beans, one of the least rich protein sources of methionine, had the highest absorption rate the amino acid.  I’m sure absorption of methionine from soy is low as well because some of the chemicals in soy interfere with overall amino acid absorption.

However, soy introduces an extremely important consideration that might make it impossible for humans to benefit from methionine restriction.  Soy contains estrogen-mimicking phytochemicals which will have some effect on producing anabolic processes. (the exact thing we’re trying to prevent to extend longevity) These chemicals must be detoxified by Phase 1 enzymes in the liver.  If this pathway is not working because of a deficiency of methionine, folic acid etc then there will be accumulation of these chemicals in the fat tissues possibly increasing incidence of hormone-sensitive cancers.  There are hundreds of anabolic hormone-mimicking chemicals that are now ubiquitous in our environment including BPA, several pesticides and hormones from pharmaceutical use. Any steps taken to reduce methionine will slow detoxification of these chemicals to a trickle.

If you want to continue to think creatively, be active, fully participate in life and be able to detoxify various environmental chemicals,  you have no choice but to consume foods that allow your body to do this.  If you want to attempt to extend your life through the means of caloric and methionine restriction then you will spend your life existing, not fully living and you might still get cancer.  Perhaps one way of using the current knowledge of caloric and methionine restriction to extend life is to follow what would naturally happen with the seasons.  For example, reduce your activity in the winter and practice caloric and methionine restriction.  Personally, I love skiing too much and need lots of protein to be able to do it.   That said, I’m going to continue to eat 8-10 eggs per week along with lots of kale.

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Bugs…Don’t Kill ‘Em, Eat Em!

“If all the insects were to disappear from the earth, within 50 years all life on earth would end. If all human beings disappeared from the earth, within 50 years all forms of life would flourish.”  Jonas Salk

In the previous posting I discussed protein requirements for present-day humans and questioned the inefficiency of the ecological model with respect to evolution. 

A couple of years ago, while pondering a failing in my second attempt at a biodynamic garden, I was looking at an infestation of insect eggs on my collard greens.  Reflecting back on an involuntary, three-day survival situation I also pondered that, by day three, those insect eggs would have looked pretty appetizing.   Sitting there, I realized that before the advent of modern farming, the plants we ate and water we drank would have been full of the products of all life stages of insects.  This is a well of protein and other essential nutrients that we have now virtually eliminated from our food supply. 

The general consensus is that, despite the ability to hunt, hunter-gatherer societies still obtained 80% of their food calories from gathering.  To help incur the survival advantage, all species in the food web (other than present-day humans) have retained the universal law of the conservation of energy.  However, the transfer of energy in the form of calories is quite inefficient.  As we move up each trophic level in the food chain only about 10% of the energy is transferred.  

For a species to skip a trophic level is an incredibly inefficient utilization of resources and is an idiosyncrasy in the natural laws.  Like lions attacking an elephant (which is rare), a species has to be under an incredible amount of stress and scarcity to expend the energy to harvest higher in the food web.  Nonetheless, due to communication, cooperation, the ability to make tools, and the ability to be omnivores, this idiosyncrasy allowed humans to expand beyond their niche and take over the Earth.  Coyotes (also omnivores) are one of the few other creatures that have managed similar success.  The difference between coyotes and humans is that coyotes remained part of the ecological web whereas humans moved beyond it.

Because insects are a much more abundant and energy-efficient protein source, they likely acted as an evolutionary bridge for humans.  Insects would have provided the all the essential amino acids as well as the essential nutrients choline and omega-3 fatty acids.  Access to these nutrients would have enabled humans to move away from coastal food dependency and more inland.  It’s possible that this protein source was more passively obtained through the consumption of plants which, as I already mentioned, would have contained insect eggs and larvae.

Insects also provide various chemicals that help to treat and prevent disease.  For example, their exoskeleton provides chitin, a key source of glucosamine which is now taken as a dietary supplement to help prevent joint tissue degeneration. Perhaps if we still ate insects we wouldn’t need to take their exoskeletons in pill form.  Several “bugs” are used medicinally in Traditional Chinese Medicine.  For example earthworms, which contain the enzyme lumbrokinase, are used to treat blood clots and congestion of tissues when there is lots of inflammation and phlegm present.  I can speak from experience that asthma patients respond profoundly better when earthworm is included in a formula.  Other medicinal insects that actually work when used appropriately include cicada skin for dry, itchy skin, and mantis egg case for urinary leakage and incontinence. 

It’s time that we move from viewing insects as pests to viewing them as a resource.  We evolved eating them.  Efforts to transcend the stigma of eating insect products in our society offer an array of benefits.  Reduction of consumption of fossil fuels to produce protein, reduction of need for pesticides in some crops, recovery of species numbers which depend on various insects as a primary food source in areas like the country’s mid-section where pesticide use results in incidental insect elimination.  In an effort to work with the natural laws I say the “Don’t kill ‘em, eat ‘em!” policy should be implemented immediately.

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