FAQs: Medline

  1. Biliverdin/Phycocyanobilin, Glycine, High-Dose Folate, and Metformin/Berberine as Antidotes to Endotoxin

    Sepsis is a leading cause of death in hospitalized patients who have developed infections with gram negative bacteria. A cell wall component in these bacteria, known as lipopolysaccharide or endotoxin, triggers this syndrome by strongly activating immune cells known as macrophages, which subsequently secrete a wide range of pro-inflammatory, pro-coagulant and vasodilatory compounds that can collaborate to induce circulatory shock and damage to vital organs. There is reason to suspect that certain available nutraceuticals and drugs – including spirulina, the amino acid glycine, the vitamin folic acid in high dose, and the anti-diabetic drug metformin – could aid survival in sepsis by blunting the production and activity of the hormone-like compounds responsible for its lethality. This essay discusses these prospects. Moreover, the mechanisms whereby Ebola infections kill their victims are quite analogous to the mechanisms involved in septic shock; hence, the protocols suggested here for managing sepsis may also have potential to aid survival in Ebola.


  2. Do GLP-1 and Glucagon Mediate Some of the Protection Afforded by Supplemental Glycine?

    The amino acid glycine, when ingested in high daily doses, has a range of promising anti-inflammatory effects, reflecting its ability to activate receptors that permit the flux of chloride ions across cell membranes. Glycine is particularly protective to rodents fed sucrose-rich diets, who otherwise develop a fatty liver, an increase in abdominal fat stores, and elevated blood pressure – a syndrome similar to “metabolic syndrome” in humans. This essay proposes that glycine’s benefit in this regard reflects increased production of two hormones – glucagon-like-peptide-1 (GLP-1) and glucagon – which act on the liver to promote that burning of fat while preventing new fat synthesis. Hence a high intake of glycine – inexpensive and pleasant-tasting – may act as an antidote to the adverse metabolic effects of diets high in added sucrose or fructose.


  3. The Protection Conferred by Chelation Therapy in Post-MI Diabetics Might be Replicated by High-Dose Zinc Supplementation

    A recent clinical trial funded by the NIH has concluded that, whereas i.v. chelation therapy is not beneficial for most patients who previously have suffered a heart attack, diabetics achieve a substantial reduction in mortality and risk for another heart attack when they receive this therapy. There is reason to suspect that chelation of copper may be responsible for this benefit, as copper catalyzes the production of toxic agents known as “advanced glycation endproducts” in diabetics. The copper chelating drug trientine shows interesting promise in studies with diabetic rodents, and in preliminary clinical trials in diabetics, but it is too expensive to be practical at present. High doses of zinc can impede dietary absorption of copper and decrease its effective availability in tissues, and hence may represent a more practical strategy for opposing the contribution of copper to the complications of diabetes.


  4. Nutraceutical and Drug Measures for Expanding the T Regulatory Lymphocyte Pool

    Immune cells known as T regulatory lymphocytes exert anti-inflammatory effects and help to ward off autoimmune disorders such as rheumatoid arthritis, ulcerative colitis, SLE, and multiple sclerosis. They may also aid in the prevention and control of neurodegenerative conditions, atherosclerosis, and metabolic syndrome. This essay cites a number of practical strategies which may have potential for optimizing the level and activity of T regulatory cells.


  5. Response to Editorial: “Enough is Enough: Stop Wasting Money on Vitamin and Mineral Supplements”

    This essay offers a vigorous response to a recent editorial in Annals of Internal Medicine that urged people to stop “wasting their money” on vitamin-mineral supplements. In fact, although most multi-vitamin-mineral supplements currently sold may offer little health benefit to people who are reasonably well nourished, the right doses and forms of many vitamins and minerals may have exciting potential for protecting health.


  6. Potential Ghrelin-Mediated Benefits and Risks of Hydrogen Water

    Ingestion of water saturated with molecular hydrogen (H2) has been widely studied in Japan recently as an antioxidant strategy. Although H2 has antioxidant potential, the elevations of H2 in blood achieved by ingesting hydrogen water are so modest and transient that it is hard to explain the intriguing effects observed with this water by an antioxidant mechanism. Very recent research in mice has discovered that drinking hydrogen water causes increase production by the stomach of the hormone ghrelin, and that ghrelin is responsible for the favorable effects on hydrogen water on mouse models of Parkinson’s disease. If hydrogen water likewise boosts ghrelin production in humans, it may have important potential for protecting the brain, vascular system, and liver, while aiding the control of inflammatory disorders.


  7. A Vegan Diet of Modest Protein Content, by Down-Regulating Akt-mTORC1 Activity in Lymphocytes, May Aid Induction of T Regulatory Cells

    Many autoimmune disorders – maladies such as rheumatoid arthritis, ulcerative colitis, and multiple sclerosis – were quite rare among sub-Saharan Africans in the middle of the last century, and also appear to have been comparatively rare in certain quasi-vegan Asian societies at the time. Vegan diets also have been reported to have some clinical efficacy for blunting the severity of rheumatoid arthritis and multiple sclerosis. This essay proposes that vegan diets may have the potential to increase the activity of immune cells known as T regulatory lymphocytes that help to prevent and control autoimmunity.


  8. “Failure to Thrive” as a Vegan – Could Supplemental Carninutrients Help?

    Although whole-food vegan diets are notably health protective in many ways, some people who have tried vegan diets, even those informed enough to supplement with vitamin B12 (absent from vegan diets), claim that they gave up this attempt because they simply didn’t feel like they had robust health at the time. It is suggested that supplementation with physiologically cofactors found in flesh foods – cofactors which aren’t truly nutritionally essential because the body can make some of their own – might improve the health and vigor of some vegans. These cofactors – dubbed “carninutrients” – include carnitine, taurine, creatine, and carnosine (or beta-alanine). A clinical study evaluating this hypothesis is recommended.


  9. GCN2 and FGF21 are Likely Mediators of the Protection from Cancer, Autoimmunity, Obesity, and Diabetes Afforded by Vegan Diets

    Vegan diets of moderate protein content, when practiced throughout life, have been linked to a markedly decreased risk for many cancers, as well as for autoimmune disorders, obesity, and diabetes. Such diets also typically lower blood levels of the hormone IGF-I, elevated levels of which may increase cancer risk. This essay proposes that the relatively low essential amino acid content of moderate-protein vegan diets activates the enzyme GCN2, which in turn promotes increased production of the protective hormone FGF21 by the liver. This increase in FGF21 may be responsible for the reduction in IGF-I production observed in vegans, and may work in other ways to lessen risk for obesity and diabetes. Activation of GCN2 within the immune cells of vegans may play a role in their lesser risk for autoimmunity.


  10. Memo: Carvedilol for Blood Pressure Control in Metabolic Syndrome and Type 2 Diabetes

    “Metabolic syndrome” – typically associated with increased abdominal fat, elevated levels of triglycerides and insulin, low HDL cholesterol, and raised blood pressure – is a key cause of vascular disease, diabetes, and cancer. This syndrome is usually associated with increased activity of the sympathetic nervous system – often manifesting as high resting heart rate and blood pressure – and such an increase appears to increase risk for vascular disorders, cancer, and total mortality. The drug carvedilol, often used to treat hypertension and heart failure, may provide notable protection to people with metabolic syndrome by blocking the effects of excessive sympathetic activity.


  11. A Whole-Food Vegan Ketogenic Diet for Treatment of Cancer

    Low-carbohydrate ketogenic diets may aid control of certain cancers by keeping glucose and insulin levels low throughout the day, and vegan diets of moderate protein content can decrease blood levels of insulin-like growth factor-I (IGF-I), a hormone which promotes proliferation and survival in many cancers. Hence, it is proposed that ketogenic vegan diets, high in fat, moderate in plant protein, and very low in carbohydrates, comprised primarily of healthful whole foods, may represent a practical strategy for slowing or even temporarily reversing the spread of some cancers.


  12. A Role for cAMP-Driven Transactivation of EGFR in Cancer Aggressiveness – Therapeutic Implications

    A signaling molecule known as cyclic AMP (cAMP) is produced in many cancers, and makes them more aggressive. Adrenergic hormones (adrenaline, noradrenaline), as well as hormones produced by the pro-inflammatory cox-2 enzyme, boost cAMP production in many cancers. Hence, drugs which block cox-2 activity, or which inhibit receptors for adrenergic hormones, may have potential for cancer prevention and control. Drugs known as beta-blockers inhibit the activity of adrenergic hormones, and some studies show that cancer patients taking certain forms of these drugs have improved survival. Hence, beta-blockers may have a future as adjuvant therapies for cancer, and might also reduce cancer risk.


  13. CK2 Inhibition May be a Key Mediator of the Cancer-Retardant Effects of Natural Flavones in Xenografted Nude Mice

    An enzyme known as CK2 is highly active in a high proportion of aggressive cancers, and functions in numerous ways to make cancers more aggressive and harder to kill. Drugs which target this enzyme are currently being developed in hopes that they can become safe and effective therapies for cancer. Certain widely distributed phytonutrients – known as flavones and flavonols – have the potential to inhibit CK2 in concentrations that might conceivably be achieved via oral administration. It is proposed that this phenomenon may account, at least in part, for the demonstrated ability of these compounds to slow the growth of human cancers implanted in mice; hence, these compounds may merit serious clinical evaluation as cancer-retardant agents.


  14. Neurosupportive Potential of Creatine Orotate

    This essay proposes that the supplement creatine orotate may work in multiple complementary ways to aid cognitive function, while protecting the brain from stroke, trauma, and neurodegenerative disorders, and also supporting efficient brain healing. It should do this by boosting brain levels of key metabolic constituents – pyrimidines, carnosine, and creatine – that support efficient function and provide protection.


  15. A Carbohydrate Concentration Regimen that Segregates Protein-Rich Foods into Low-Carb Meals May Represent a More Practical Way to Achieve the Healthspan Benefits Conferred by Calorie Restriction or Alternate-Day Fasting

    Calorie restriction and alternate-day fasting boost healthspan and lifespan in rodents and other species, and can promote leanness, but are too rigorous for most people to stick with as a lifestyle. This essay reviews proposed alternative strategies that have the potential to achieve a measure of the same benefits, but with greater practicality. Carbohydrate concentration diets, in which the bulk of the day’s carbohydrate intake is confined to one meal daily, and insulin levels are kept low for most of the day, are likely to be useful in this regard, and are highly practical, since people are allowed to eat three meals daily and consume the foods they like – albeit at specified times of day. The efficacy of this approach can be amplified by excluding protein-rich foods from the high-carbohydrate meal, inasmuch as co-ingestion of protein can markedly boost the insulin response to ingested carbohydrate. Hence, in this strategy, high-carb/low-protein meals are alternated with high-protein/low-carb meals, the intent being to minimize daily insulin secretion. Maintaining lower insulin levels decreases the growth factor activities which drive the aging process and cancer induction, while also promoting the burning of stored or ingested fat.


  16. Memo: Is Peroxynitrite a Mediator of Survival and Aggressive Growth in Pancreatic Adenocarcinoma?

    Pancreatic adenocarcinomas tend to generate both superoxide and nitric oxide, and both of these factors aid the survival and spread of the cancer. This essay raises the possibility that a portion of this effect is mediated by peroxynitrite, which forms spontaneously when superoxide and nitric oxide react. If so, high-dose folate might be useful for treating this cancer, as intracellularly folates can scavenge radicals derived from peroxynitrite. Spirualina also may be helpful, by inhibiting the enzymatic complex that is the chief source of the superoxide.


  17. Memo: PNC-27, a Peptide that Induces Necrosis Selectively in Cancer Cells

    Cancer scientists at State University of New York have developed a protein that can punch holes in the walls of cancer cells, leading to their death. This phenomenon appears to be selective to cancer cells, and is more likely to work in cancers that are advanced and aggressive. Continual infusion of this protein suppresses the growth of pancreatic cancer in mice – without evident harm to the mice — so this protein may have potential as a very novel cancer drug.


  18. NADPH Oxidase as a Mediator of Calcium Oxalate Nephrolithiasis

    The most common type of kidney stone is composed of calcium oxalate. Oxalate can act on the kidney tubules to induce oxidative stress via NADPH oxidase, and this plays a role in the promotion of stone formation. This explains why phycocyanin from spirulina has shown value for preventing calcium oxalate stones in rodent studies.


  19. Are Antioxidants Bad for Us? — A Response to Dr. Paul Offit

    Pediatrician Dr. Paul Offit has been creating a bit of a stir with his new book, Do You Believe in Magic? The Sense and Nonsense of Alternative Medicine. Although many of the targets he takes on are no doubt worthy of attack, he also takes a broad swipe at supplemental nutrition, implying that it is useless if not harmful. He focuses in particular on antioxidant supplementation, claiming that clinical research has shown it to be counterproductive. Several excerpts from his book attacking supplementation have been reprinted in venues such as New York Times Sunday Review and The Atlantic magazine. Here is a not-very-technical rejoinder to Offit’s negative views on supplementation.


  20. Stroke Prevention in a Nutshell

    A concise summary of lifestyle strategies for reducing your risk for stroke.


  21. Ambient Cadmium Importantly Up-Regulates Systemic Oxidative Stress

    The most recent epidemiology on cadmium suggests that exposure to this toxic metal may be responsible for a high proportion of cases of breast and pancreatic cancer in people who have not experienced industrial cadmium exposure. It also suggests that cadmium boosts oxidative stress throughout the body, an effect which likely mediates much of its toxicity.


  22. Phycocyanobilin from Spirulina — the Master Antioxidant

    The chief source of oxidative stress in many health disorders is the NADPH oxidase complex; in many of these disorders, the oxidants produced by this complex either cause the syndrome, or at least make it worse. Although the natural metabolite bilirubin functions as a potent inhibitor of NADPH oxidase, it is not practical to use this compound as a supplement. Fortunately, the blue-green algae spirulina is a very rich source of a chemical relative of bilirubin, known as phycocyanobilin (PhyCB), that likewise can potently inhibit NADPH oxidase. This probably explains why spirulina has shown such a broad range of protective anti-inflammatory effects in rodent studies. Hence, it seems likely that regular ingestion of adequate amounts of spirulina – perhaps in the range of 1-2 tablespoons daily – can make a great contribution to health. This essay provides some practical tips on spirulina supplementation.


  23. Interleukin-6 and Tumor Necrosis Factor-alpha, Which May Boost Homocysteine by Decreasing Hepatic S-Adenosylmethionine, May Mediate the Cardiovascular Risk Associated with Moderately Elevated Homocysteine

    Although moderate elevations of the metabolite homocysteine (hcy) correlate with increased risk for heart attack and stroke, the failure of vitamin therapies which lower hcy to reduce vascular risk reveals that moderately elevated hcy per se does not cause heart disease. Why then do hcy levels correlate with risk? It is proposed that hcy levels are often elevated because of the actions of the hormone-like compounds interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) on the liver – and that these hormones do indeed promote vascular disease, in part by inducing the liver to make the pro-inflammatory factor serum amyloid A. Hence, lowering the level or the activity of IL-6 and TNF-alpha may be expected to alleviate the excess cardiovascular risk associated with elevated hcy.


  24. Practical Strategies for Suppressing Hypoxia-Inducible Factor Activity in Cancer Therapy

    Anti-angiogenic strategies for controlling cancer – measures which slow cancer growth and spread by blocking the growth of new blood vessels required for tumor expansion – were initially considered to have great promise, but in practice have usually had only a modest impact on survival statistics owing to adaptations by the cancer that help it to survive in a low oxygen environment and increase its ability to elicit blood vessel growth. In particular, increased activity of the protein hypoxia-inducible factor-1 (HIF-1) is evoked by anti-angiogenic therapy, and helps the cancer to adapt in this way. This essay describes a range of feasible measures that might be employed to suppress HIF-1 activity in cancers, potentially making anti-angiogenic therapy more effective.

    Published in Medical Hypotheses 2010;74(5):789-97.


  25. Expression and/or Activity of the SVCT2 Ascorbate Transporter May be Decreased in Many Aggressive Cancers, Suggesting Potential Utility for Sodium Bicarbonate and Dehydroascorbic Acid in Cancer Therapy

    Within cancer cells, vitamin C (ascorbate) performs the key function of controlling the activity of hypoxia-inducible factor-1 (HIF-1), a protein which helps cancer cells to thrive in low oxygen conditions and makes them much more aggressive. But there is evidence that in at least some cancers, their ascorbate content is too low to optimally control HIF-1 activity – and unfortunately simply ingesting more vitamin C is unlikely to correct the problem. However, the vitamin C metabolite dehydroascorbic acid can get into cancer cells efficiently – and once inside the cell is rapidly converted to ascorbate. So it is proposed that regular intravenous infusions of dehydroascorbic acid could be employed to optimize the ascorbate content of cancers, and thereby help control their aggressiveness.


  26. Rationale for a Novel Nutraceutical Complex ‘K-Water: Potasssium Taurine Bicarbonate (PTB)

    This essay proposes a nutraceutical water – “K-Water” – enriched with potassium bicarbonate and taurine, as a practical strategy for boosting daily intakes of potassium, taurine, and organic base. Despite its potassium content, the flavor of this water is almost indistinguishable from that of ordinary water unless acidic compounds are added. There is reason to suspect that regular ingestion of K-Water could aid blood pressure control, lessen risk for atherosclerosis and its complications (particularly stroke), aid maintenance of bone density, and lessen risk for kidney stones.

    Published in Medical Hypotheses 2006;67(1):65-70


  27. Isoflavones Made Simple – Genistein’s Agonist Activity for the Beta-Type Estrogen Receptor Mediates Their Health Benefits

    The isoflavone phytochemicals in soy foods are often misleading refered to as “weak estrogens”. In fact, there are two types of estrogen receptors, ERalpha and ERbeta. ERalpha activity is responsible for the feminizing and pro-carcinogenic effects of estrogen, whereas ERbeta activity is not feminizing, and tends to oppose the cancer-promoting activity of ERalpha. When people ingest feasible amounts of soy foods, the blood levels of the free isoflavone genistein become just high enough to effectively activate ERbeta, but are too low to meaningfully activate ERalpha – that’s why soy foods don’t cause feminizing effects in men. Genistein’s ability to selectively activate ERbeta helps to explain reports that frequent soy ingestion is linked with lower rates of breast, prostate, and colon cancer, yet is not associated with the pro-thrombotic effects of oral estrogen. Postmenopausal women are relatively protected from kidney disease and heart failure; this protection appears to be mediated by ERbeta, and hence might be replicated with soy foods. ERbeta has a small favorable impact on bones and the endothelial lining of arteries, and hence soy foods may be modestly beneficial for bone and vascular health, although they have less impact in this regard than hormonal estrogens. In short, regular ingestion of soy isoflavones appears to offer meaningful protection from several common cancers, and to provide some of the health benefits associated with estrogen activity, without the major risks.

    Published in Medical Hypotheses 2006;1093-114.


  28. Practical Strategies for Targeting NF-kappaB and NADPH Oxidase May Improve Survival During Lethal Influenza Epidemics

    Perhaps surprisingly, the “killer” influenzas do not kill by the direct damaging impact of the flu virus on lung tissue, but rather by the over-exuberant immune response which such infections can evoke – effectively filling the lungs with fluid. An analysis of the mechanisms responsible for this inflammation leads to the proposal that administration of spirulina, N-acetylcysteine, and the drug salsalate, initiated as soon as possible after the onset of infection, may dampen the evoked inflammation and hence lessen the lethality of “killer” flus.

    Published in Medical Hypotheses 2010;74(1):18-20.


  29. Clinical Potential of Phycocyanobilin for Induction of T Regulatory Cells in the Management of Inflammatory Disorders

    Recent studies indicate that the natural metabolite bilirubin, in addition to its profound antioxidant effect, also plays a key role in the induction of “T regulatory cells” – immune cells which play a key role in preventing or controlling autoimmunity and inflammation. There is now reason to suspect that the phycocyanobilin (PhyCB) richly supplied by spirulina, a close structural relative of bilirubin, likewise has the potential to promote induction of T regulatory cells. This could help explain the remarkable anti-inflammatory activity associated with orally administered spirulina (or spirulina extracts) in a number of rodent models of autoimmunity. Since PhyCB is also a potent antioxidant, it hence may provide a “one-two punch” against inflammatory and autoimmune disorders.

    Published in Medical Hypotheses 2011;77(6):1031-3.


  30. Dietary Saturate/Unsaturate Ratio as a Determinant of Adiposity

    Diets in which the ratio of saturated to unsaturated fats is low – such as “Mediterranean” or most plant-based diets – tend to be associated with good muscle insulin sensitivity and a compensatory reduction of daily insulin secretion. Since insulin acts on the body’s fat cells to promote storage, retention, and synthesis of fat, it is proposed that reduced daily insulin secretion may help to account for the relative leanness of people who are long-term practitioners of vegan or Mediterranean diets low in saturated fat.

    Published in Medical Hypotheses 2010;75(1):14-6.


  31. Phycocyanobilin and Dietary Nitrate May Exert Natriuretic Effects That Suppress Production of Marinobufagenin

    There is reason to suspect that both dietary nitrate – found in green leafy vegetables and beets – and the key phytochemical in spirulina, phycocyanobilin (PhyCB), can act on the kidneys to promote more efficient excretion of sodium, owing to their ability to boost the bioactivity of the protective hormone nitric oxide while controlling oxidative stress. This in turn would be expected to lessen adrenal production of marinobufagenin, a hormone suspected to mediate both the increase in blood pressure, and the increased risk or vascular diseases, associated with salt-sensitive hypertension. Nitrate and PhyCB might also act directly on MBG’s target tissues to lessen its pathogenic impact.


  32. Marinobufagenin and Cyclic Strain May Activate Endothelial NADPH Oxidase, Contributing to the Adverse Impact of Salty Diets on Vascular and Cerebral Health

    In people said to be “salt-sensitive”, a salty diet provokes a temporary fluid overload that is compensated by adrenal secretion of the hormone marinobufagenin (MBG). Although MBG acts on the kidneys to promote sodium and fluid excretion, it also acts on vascular smooth muscle to increase the peripheral resistance to blood flow, raising blood pressure. But the pathogenic impact of salt-sensitive hypertension is greater than can be explained by an increase in hydrostatic pressure alone, and so MBG is suspected to exert additional deleterious effects. MBG is capable of exerting hormone-like effects on certain cells by interaction with the “sodium pump”. It is proposed that one of these hormonal effects is to increase activity of the enzyme NADPH oxidase in the endothelial lining of blood vessels; this might account for the oxidative stress and pro-inflammatory behavior noted in the endothelium of people with salt-sensitive hypertension, and could help to explain the excess vascular risk associated with this disorder.

    Published in Medical Hypotheses 2012;78(2):191-6.


  33. Minimizing the Cancer-Promotional Activity of Cox-2 as a Central Strategy in Cancer Prevention

    Recent analyses of large controlled trials evaluating daily low-dose aspirin reveal that this strategy is associated with a notable reduction in cancer mortality. There is reason to suspect that this reflects aspirin’s ability to inhibit the pro-inflammatory enzyme cox-2. This essay reviews a number of additional measures that are suspected to decrease cancer risk – including spirulina, phase 2-inductive phytochemicals, melatonin, vitamin D, soy isoflavones, vegan diets, leanness, exercise, and a low dietary omega-6/omega-3 ratio – and notes that at least a part of their protection may be afforded by a reduction in cox-2 activity. While maintaining a focus on cox-2, this article provides an overall summary of practical strategies for cancer prevention.

    Published in Medical Hypotheses 2012;78(1):45-57.


  34. A “Mini-Fast with Exercise” Protocol for Fat Loss

    Nesting sessions of moderate intensity aerobic exercise within 12-14 hour fasts is a logical and effective strategy for burning off stored fat; that’s because insulin and glucose levels remain low during and for some time after the exercise. If you choose low-fat foods when you do eat, progressive fat loss is almost assured. This “mini-fast with exercise” strategy was tested in an open clinical trial at Oasis of Hope Hospital; on average those who finished the 12-week protocol lost a quarter of their initial fat mass, while actually increasing their lean mass. This is a sustainable strategy that can help to achieve and maintain leanness; it is compatible with carbohydrate concentrated-dieting, and with vegan or Mediterranean dietary choices.

    Originally published in Medical Hypotheses 2009;73(4):619-22.


  35. AMPK Activation – Protean Potential for Boosting Healthspan

    Proposes that drugs, phytochemicals and foods capable of activating the enzyme AMP-activated Kinase (AMPK) may literally slow the aging process in some key respects – and potentiate the utility of carbohydrate-concentrated diets in this regard. Presents evidence that AMPK activation may have a favorable impact on risks for vascular disorders, cancer, diabetes, obesity, neurodegenerative diseases, osteoporosis, osteoarthritis, and autoimmunity.


  36. Mini-Fast with Exercise — My Personal Experience

    A straightforward, non-technical narrative which describes how the mini-fast with exercise strategy for leanness was developed.


  37. Induction of Hepatic Uncoupling Protein 2 May Mediate the “Metabolic Advantage” of Ketogenic Diets

    An attempt to explain why people on very-low-carb ketogenic diets tend to lose weight and body fat faster than people eating higher carb diets of the exact same calorie content. Proposes that activation of thermogenic (heat generating) processes in the liver may account for this.


  38. Ketosis May Promote Brain Macroautophagy via Activation of Hypoxia-Inducible Factor-1

    Suggests that a portion of the favorable impact of ketosis on brain function and health may reflect activation of the “cell cleansing” process known as macroautophagy in brain neurons. Proposes a mechanism whereby ketosis might achieve this.


  39. Could Carbohydrate -Concentrated Diets Mimic Calorie Restriction in Slowing the Aging Process?

    A summary of the evidence supporting the utility of carbohydrate-concentrated diets for enhancing healthspan while promoting leanness. Delves into the molecular biology which may mediate these benefits.


  40. The NIA and Wisconsin Rhesus Calorie Restriction Studies – Some Comments

    This article attempts to rationalize the contrasting results of the rhesus monkey calorie restriction longevity studies still in progress at the National Institutes of Aging and the Wisconsin National Primate Research Center. The “take home” lesson from this analysis is that relatively modest degrees of calorie restriction – analogous to the 11% or so calorie restriction once practiced by long-lived Okinawans – may be sufficient to achieve an optimal prolongation of longevity in humans. Quite conceivably, a carb-concentrated diet may enable many people to achieve calorie restriction of this magnitude, without the inconvenience of calorie counting.


  41. A Safe Strategy for Control of Hyperalgesia – Boswellic Acids, Phycocyanobilin, and Salsalate

    In states of chronic inflammation or nerve damage, nature often pulls a cruel trick by boosting the sensitivy of the nervous system to painful stimuli – a phenomenon known as hyperalgesia. NSAIDS and opiates are often used to treat hyperalgesia, but their long-term use is beset by side effects and development of tolerance. This essay proposes that a regimen combining several natural agents – boswellic acids, phycocyanobilin (from spirulina), and salsalate (a delivery form of the phytochemical salicylic acid) – may have potential for controlling hyperalgesia, while posing less toxic risk.


  42. Vaccination with Heat-Shocked Mononuclear Cells as a Strategy for Treating Neurodegenerative Disorders Driven by Microglial Inflammation

    Proteins produced in heat-stressed cells, known as heat-shock proteins, can promote the activation of a type of immune cell – T regulatory lymphocytes – that functions physiologically to suppress inflammation. By exposing human blood cells to a survivable heat stress in the laboratory, and then injecting them into patients with autoimmune diseases or other inflammatory disorders, it is possible to vaccinate patients with heat shock proteins, thereby activating T regulatory lymphocytes that suppress their inflammation. This strategy may have potential for treating various neurodegenerative disorders – such as multiple sclerosis and Parkinson’s disease – as well as major depression, which may be driven or exacerbated by inflammation in certain regions of the central nervous system.


  43. β-Boswellic Acid, A Safe and Clinically Effective Inhibitor of Prostaglandin E Synthase-1, Has Potential for Prevention of Cancer, Alzheimer’s Disease, and Vascular Disorders, and for Control of Inflammatory Pain

    Frankincense, rich in compounds known as boswellic acids, is a natural tree resin extract that has long been used in Ayurvedic medicine for treatment of inflammation. Recent research suggests that its utility in this regard reflects the ability of beta-boswellic acid to inhibit an enzyme, microsomal prostaglandin E synthase-1, that produces the mediator of inflammation prostaglandin E2. The anti-inflammatory efficacy of NSAID drugs such as ibuprofen also largely reflects their ability to inhibit prostaglandin E2 production, but they have a different target (the enzyme cyclooxygenase) and have important side effects and risks, whereas boswellic acids appear quite safe. Administration of boswellic acids may therefore represent a way to achieve some of the benefits associated with chronic NSAID therapy – such as prevention of various cancers and Alzheimer’s disease – at minimal risk.


  44. Low-Fat, Low-Salt, Whole-Food Vegan – Staying Lean and Healthy into Ripe Old Age

    A whole-food plant-based diet, relatively low in fat and added salt, has tremendously versatile potential for health protection. This monograph sets forth the scientific evidence which suggests that this strategy can prevent or stop the progression of vascular disease; prevent and reverse obesity and type 2 diabetes; decrease risk for hypertension, stroke, and dementia; reduced risk for many types of cancer, while aiding control of some cancers; prevent and treat autoimmune disorders; aid preservation of bone density; reduce risk for prostate hyperplasia, gallstones, renal stones, diverticulitis, appendicitis, and more – all while minimizing waste of finite planetary resources and combatting global warming. Over 1200 pertinent scientific papers are cited.


  45. Overview of Macrophage Activating Factor and the Nagalase Assay – Potential for Control of Micrometastatic or Early Primary Cancer

    This essay reviews the evidence currently available on macrophage activated factor (GcMAF) as a treatment for cancer, and on serum nagalase as a putatively universal marker for cancer. Studies by Yamamoto and colleagues suggest that, when cancer is in a micrometastatic form follwing therapeutic extirpation of visible tumors, weekly injection of GcMAF may enable the macrophage-orchestrated immune response to eliminate the residual cancer cells, effectively achieving a cure. Repeated assays of serum nagalase may enable monitoring of cancer status during such therapy, revealing whether the therapy is working, and providing guidance as to how long the therapy should be continued. Much further research is required to confirm these possibilties. The use of GcMAF in conjunction with other agents that boost the tumor-kiling potential of macrophages may be a promising approach to cancer immunotherapy that should be evaluated.


  46. Injections of Macrophage Activating Factor May Have the Potential to Cure Cancer Patients with Minimal Residual Disease – and Now Can be Self-Administered by Patients

    There is now strong reason to suspect that a natural protein, made in our bodies to boost the microbe- and cancer-fighting abilities of immune cells known as macrophages, can help to cure cancer when injected repeatedly by cancer patients who have minimal disease following successful surgery, chemotherapy, or radiotherapy.  This agent – macrophage activating factor (abbreviated as “GcMAF”) also may have the potential to slow cancer spread in patients with more advanced cancers, although this is more speculative.  And the good news is that, although GcMAF hasn’t yet received drug approval (and may be unlikely to, owing to the fact that it is a natural compound), it currently can be ordered via email from several chemical companies, who ship it in a form suitable for intramuscular administration (much like insulin). More scientific detail →


  47. Serum Bilirubin May Serve as a Marker for Increased Heme Oxygenase Activity and Inducibility in Tissues – a Rationale for the Versatile Health Protection Associated with Elevated Plasma Bilirubin

    Elevated serum levels of the antioxidant bilirubin tend to be associated with lower risk for cardiovascular disease and many other disorders, but people who have elevated bilirubin owing to their expression of a low-activity form of an enzyme that aids bilirubin excretion, do not enjoy such protection. This essay proposes that elevated serum bilirubin can serve as a marker for an increased propensity to generate bilirubin within tissues, and it is this propensity, rather than an elevation of serum bilirubin per se, that is responsible for the health protection associated with elevated serum bilirubin levels.


  48. Targeting Adipocytes in Metabolic Syndrome – Spirulina and Salsalate May Complement the Benefits of PPARgamma Agonists

    Metabolic syndrome, an important cause of vascular disease and type 2 diabetes, and a risk factor for cancer, is driven by an inflammatory state that arises in overstuffed fat cells (adipocytes). The diabetes drug pioglitazone (Actos) is useful for dampening this adipocyte inflammation and ameliorating metabolic syndrome, but has side effects which limit its broad use. This essay proposes that spirulina and salsalate also have the potential to act directly on adipocytes to quell inflammation, and may complement the utility of pioglitazone in this regard, or be employed as an alternative approach to improving adipocyte function.


  49. Strategies for Controlling Serum Amyloid A, a Key Mediator of the Impact of Systemic Inflammation on Cardiovascular Disease

    Although a systemic inflammatory state associated with elevated C-reactive protein (CRP) is clearly associated with increased cardiovascular risk, CRP per se does not appear to mediate this association. There is better reason to suspect that elevated serum amyloid A – like CRP, an “acute phase reactant” produced by the liver – is a true cause of cardiovascular disease. This essay suggests that the liver’s production of serum amyloid A could be suppressed by various agents, including spirulina, salsalate, metformin or berberine, and tocotrienols.


  50. Folate Deprivation/Antagonist Therapy for Early Stage Prostate Cancer

    Prostate epithelium, and some early prostate cancers, appear to require higher concentrations of folic acid than most other tissues to support a maximal rate of cellular multiplication. Therefore, a low-folate diet and/or low doses of the folate antagonist methotrexate may have the potential to slow the onset and growth of early stage prostate cancer – a possibility that could be tested clinically.


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