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Quoting Ezekiel Emanuel: "Personally, despite being taught the Krebs cycle (twice during medical school as well as twice in college), I have never used it in my practice or research."
What a terrible shame! The Krebs cycle is so fundamental to... well, to damn near everything, that to ignore it is to ignore a significant portion of the biochemical fundament of healing. I was not taught the Krebs cycle twice. I taught myself the Krebs cycle several times, and have contemplated it for years -- especially in its context as the biochemical mechanism most prominent in mitochondrial function. This is the very basis of cellular health and integrity, EVERY aspect of which depends on the energy compounds generated in the mitochondria (by way of the Krebs cycle). The pertinence of energy to all biological systems and functions can be reflected in mythic terms: "energy is eternal delight" (Blake). That would be apart from eternal adequate cell function, maintenance and repair.
One non-mythic example: a tired, run-down friend of mine was suffering with a high-pressure job and wondering if she was going to be able to cut it. (She is an RN on a trauma unit, by the way, and in this case one of the traumatized was HER.) I suggested a program of what I described, for simplicity's sake, as "mitochondrial nutrients". The basic routine was: a gram or two each of powdered carnitine, ascorbic acid, and potassium bicarb, stirred into water (makes a nice alka-seltzer-like fizzzz) twice daily, combined with a B-50 (B-complex) tablet, and a lipoic acid capsule (100 or 200 mgs). The combination of carnitine and lipoic is known to activate aged or flagging mitochondria (search engine for "bruce ames", "mitochondria", and the compound names); carnitine alone in multi-gram doses often has nice ergogenic/anti-fatigue effects. The potassium is an intracellular essential for all enzyme activity, and I had reason to suspect she was K-depleted. The ascorbic helps correct the generally-universal hypoascorbemia, as well as being a great anti-stress compound (e.g. throwing the switch to send precursors toward DHEA instead of cortisol in the adrenals). It also imparts a pleasant tartness, to counteract the brackish and metallic potassium bicarb. The B-complex was a general measure to ensure full repletion and tissue saturation with the essential coenzymes -- particularly but not exclusively NAD, and others in the coenzyme-hungry mitochondria.
The result was excellent. Her fatigue quickly vanished, and her confidence and general resilience were restored. As she described it (paraphrased): "it is like drinking liquid energy... you can feel it activating all your cells within minutes", or words to that effect. Those were HER words. I had promised nothing of the sort. I told her that the effect, if any, would likely be subtle, developing over several days or weeks, so be patient. As it turned out, happily, she did not have to be patient. (I love it when that happens.) She also noted an improvement in her skin -- less wrinkles, and a fuller, more-hydrated look (less piqued). That's understandable. Potassium depletion and sodium predominance tends to dehydrate, shrink and shrivel things. And taking a big dose of potassium in the evening (best time to replete with potassium) is known in nutritional folklore circles to act as an "overnight face-lift". (Try it. It really does work, often.)
In any case, most people are potassium-depleted at the cellular level even if normokalemic (same with magnesium); most people are also slightly acidotic. Correction of this is absolutely essential to anything properly called healing. The potassium depletion, associated with chronic low-level acidosis, started with the advent of the neolithic: : Eur J Nutr. 2001 Oct;40(5):200-13 : Diet, evolution and aging--the pathophysiologic effects of the : post-agricultural inversion of the potassium-to-sodium and : base-to-chloride ratios in the human diet. : Frassetto L, Morris RC Jr, Sellmeyer DE, Todd K, Sebastian A. : PMID: 11842945 [I could give many more citations on this]
And, regarding the primacy of mitochondrial function, a fellow by the name of Richard Fiddian-Green has had many fascinating things to say -- including that mitochondrial malfunction is the likely undergirding (though perhaps not quite "cause" in the conventional sense) of a range of chronic diseases such as CAD, type 2 diabetes, COPD, hypertension, MS, depression, Alzheimer's, Parkinson's, and many more. He is no doubt correct, provided we understand the concept of terrain, or "the patient that has the disease, rather than the disease the patient has". Further, he suggests that many commonly-used drugs are acting as inhibitors of mitochondrial function -- really an alarming charge, if correct. That would mean that the CURING is going on while the HEALING is actively thwarted! Here are a few snippets from Fiddian-Green's writing: ITEM: : http://bmj.bmjjournals.com/cgi/eletters/325/7370/913 :
"An impairment of mitochondrial oxidative phosphorylation : appears to be the primary cause of organ dysfunctions and : failures including psychiatric disorders in the acutely and : possbily even in the chronically ill (2-17). The commonest : causes of impaired mitcohondrial oxidative phosphorylation are : an impairment of oxygen and/or nutrient delivery and the many : inhibitors or uncouplers of oxidative phosphorylation which : may be contained in recreational drugs, medications prescribed : and/or environmental pollutants. The impairment may on : occasions be due to increasing the demand for energy from ATP : hydrolysis beyond the capacity of mitochondria to replenish : their ATP stores." ITEM: :
http://bmj.bmjjournals.com/cgi/eletters/325/7366/701#25874 : "Both acute and chronic psychiatric disorders might be the : products of an energy deficit, that is to say an impairment of : the adequacy of mitochondrial oxidative phosphorylation and : accompanying generation of free radicals (2,3). : Antidepressants cause neuronal cell death (4). Fluoxetine : hydrochloride, protriptyline hydrochloride, amoxapine and : doxemine hydrochloride might do so by interfering with : mitochondrial oxidative phosphorylation and hence promoting : the generation of free radicals (5,6,7,8). These potentially : harmful effects are not limited to antidepressants, : haloperidol having similar effects (9)." : [...snip...] : "Drugs and hormones that exert their actions by stimulating : the release of cAMP do so at the expense of ATP from which : cAMP is derived. In circumstances in which the ability of : mitochondrial oxidation to replenish ATP stores is compromised : these drugs and hormones have, therefore, the potential to : compound the severity of the energy deficit present. As an : impairment of oxidative phosphorylation is accompanied by a : fall in tissue pH, enzyme kinetics are changed potentially : changing not only the efficacy of the drugs but also inducing : the expression of rogue genes." I
TEM: : http://www.chestjournal.org/cgi/content/full/116/6/1839 : "[T]he severity of tissue acidosis in anaerobiosis is related to : the degree of impairment of oxidative phosphorylation... Gastric : pHi [intramucosal pH] is a metabolic signal of tissue hypoxia." : [...snip...] : "[C]ontinued accumulation of protons and later net ATP degradation : compromises essential ATP-dependent functions, such as the sodium : pump, and cells swell and die. ATP degradation allows free : radicals to be generated on resuscitation." : [...snip...] : "[M]easures directed toward preventing a fall in gastric pHi5 : and restoring the gastric pHi to normal in a timely manner in : anaerobiosis are associated with improved outcomes and reduced : ICU and hospital stays and costs.6 7 8 9" MORE, see: http://bmj.bmjjournals.com/cgi/eletters/325/7375/1255
For a moment, consider also the glucose-insulin-potassium (GIK) solutions used for decades in cardiology. The idea is to drive potassium and glucose into the mitochondria-rich cardiac cells, and give them a boost of energy: the glucose as the calorific energy source, and the potassium as enzyme activator. It was a very good idea, based on understanding of cell physiology basics. Of course it would be much more effective if one were to toss in some magnesium, B-complex, lipoic acid, carnitine, coenzyme Q10, taurine and so on. Whatever. For its time, and even still today, it was and is quite good. In this instance, CURATIVE medicine, perhaps inadvertantly, stumbled upon a HEALING technique. Unfortunately, however, the healing aspect was never grasped. (Winnie Churchill's remark springs to mind: "Many people stumble over the truth, but then pick themselves up and hurry off as though nothing had happened.") For decades, GIK has been bound hand and foot, and restricted to the role of CURE for acute MI, etc. -- in which capacity it performs fairly well. This restriction bespeaks a profound lack of vision. It misses the vast potential of what might be called the "mitochondrial/bioenergetic orientation", or simply an awareness of cell physiology basics followed by application of appropriate nutrient/coenzyme arrays; i.e. HEALING at the biochemical and cellular level. That, combined with a focus on the vertical -- i.e. not waiting until the subject is horizontal, on a gurney, with cardiac arrest. But such was not to be, and in the last analysis (if you'll pardon that trite expression) it really ought not be.
Yes, such ideas could be awkwardly retro-fitted onto cure-based conventional medicine -- calling it "mitochondrial/bioenergetic medicine" or "Krebs-cycle-based medicine". But that would take decades, and would rely on the ridiculous delivery system (a cluster-fuck of impossibly-expensive institutions, bloated salaries, armies of lawyers, and all the rest) that turns a 1.2-cent aspirin tablet into a $10.95 aspirin tablet. Forget it! Let cure-based conventional medicine be cure-based conventional medicine. Meanwhile, practice health and healing, cheaply, yourself and for/with friends. The total cost of treatment for my RN friend was perhaps 15 cents per day, which includes my consulting fee of $00.00. The same kind of consulting (albeit without quite my depth of knowledge of this stuff) could be performed by any reasonably-intelligent person after several hours of study. It is not rocket science, though it CAN be if you insist on digging deep (unnecessary for daily practice). We don't need more doctors and Phds; we need more conscientious and fairly-knowledgeable caring friends. Besides, names such as "Krebs-cycle-based medicine" are too narrow. We're talking about a whole-terrain orientation, not focussed sheerly on mitochondria and Krebs cycles, however important they are.
SO, to return to the good doctor's remark -- "I have never used [the Krebs cycle] in my practice or research" -- all I can say is that he has missed-out on something at the core of healing, and fundamental to it, though he may continue to be very good at curing. And that is appropriate. Let medicine go on curing, curing, curing, but let us never confuse that with healing and health. The "health care" system must be renamed the "disease care" system, for proper perspective. Curing is a good thing and I am not opposed to it. I just want it to be placed in proper perspective. It is good, but very limited in terms of enduring benefits and true quality of life, plus it gets ruinously expensive in short order. And three cheers for the Krebs Cycle! May it long inform the work of healers, and restore the health of billions -- one educated individual at a time. Alan Lewis [aelewis AT provide DOT net]