FAQs: Miscellaneous Essays

  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. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. Age-Related Macular Degeneration – Potential Roles for Nutraceuticals in its Prevention and Control

    Age-related macular degeneration (AMD) is the leading cause of partial blindness in the elderly. This essay reviews what is known of its origins, emphasizing evidence that oxidative stress is a key mediator of this syndrome, and summarizing evidence that fish oil omega-3 fats, the carotenoids lutein and zeaxanthin, as well as a range of other antioxidants, may have be useful for preventing or slowing it. Suggestive evidence that the B vitamin folic acid, as well as soy isoflavones, may also aid control of AMD is presented.

  20. NADPH Oxidase May be a Primary Mediator of the Adverse Effects of Cigarette Smoke and of Complement Activation on Retinal Pigment Epithelium during Induction of Age-Related Macular Degeneration

    Retinal pigmented epithelial (RPE) cells play a number of crucial roles in supporting healthful function of the retina. Oxidative stress in RPE cells is suspected to be a key factor in the onset of age-related macular degeneration (AMD), but the chief source of this oxidative stress has not been clarified. This essay proposes that the increased risk for AMD seen in smokers, as when as in people who inherit certain variant genes that promote activation of blood proteins known as complement, reflects oxidative stress induced by NADPH oxidase complexes in RPE cells. If this view is correct, spirulina, which has potential for controlling NADPH oxidase activity, may have value in the prevention and treatment of AMD.

  21. Roles of Oxidative Stress in the Pathogenesis of Hepatitis C – Implications for Full-Spectrum Antioxidant Therapy with Phlebotomy

    Although our capacity to detect hepatitis C in the blood has greatly reduced transmission of this disorder via blood transfusion, this infection is still very common worldwide, and remains the leading reason for liver transplantation in the U.S. There is considerable evidence that oxidative stress in the infected liver is a key driver of the long-term deadly complications of hepatitis C – liver cirrhosis and hepatic cancer – and may also make the virus more difficult to eradicate with interferon/ribavirin therapy. This essay proposes that spirulina, high-dose folic acid, and additional antioxidants such as astaxanthin, lipoic acid, N-acetylcysteine, and silymarin, may have the potential to make chronic hepatitis C infection less dangerous, and to improve its responsiveness to proven anti-viral therapy. Depletion of liver iron by repeated blood drawing – phlebotomy – also seems likely to be of benefit in this regard.

  22. A Potential Role for Spirulina in the Prevention and Management of Preeclampsia

    Preeclampsia, a disorder of pregnancy in which the placenta fails to form properly, is a leading cause of fetal prematurity, growth retardation, and mortality, and can even endanger the life of the mother if not treated properly. Oxidative stress, within both the placenta and the mother’s circulation, appears to play a key role in driving this syndrome. This essay proposes that spirulina, a nutrient-rich whole food with outstanding antioxidant properties – and with anti-teratogenic effects in rodent studies – may prove useful for the prevention and control of pre-eclampsia.

  23. Novel Prospects for Managing Cystic Fibrosis<

    Cystic fibrosis (CF) is the most common genetic disorder in Caucasians that ultimately leads to premature death. Owing to genetic absence of a functional chloride channel, patients with cystic fibrosis experience chronic lung inflammation, mucus obstructions, and frequent lung infections, resulting in progressive structural damage to the lungs. Fortunately, therapeutic advances have increased life expectancy in this disorder, and there is reason to suspect that certain additional drug or nutraceutical measures might prove beneficial as adjuvants. This essay reviews some of the key mechanisms thought to be responsible for lung dysfunction in CF, and proposes that these might be alleviated to some extent by metformin or berberine, salsalate, a range of antioxidants including lipoic acid, spirulina, and N-acetylcysteine, and the amino acid citrulline. An Addendum appended to the end of the manuscript suggests dose ranges for these agents.

  24. High-Salt, Low-Potassium Diets May Increase Risk for Type 2 Diabetes via Marinobufagenin-Mediated Potentiation of Glucolipotoxicity in Pancreatic Beta Cells

    A couple of recent Finnish epidemiological studies have yielded that novel conclusion that a high-salt diet may increase risk for type 2 diabetes. This article proposes that high salt intakes in salt-sensitive subjects, by increasing the production of a pro-oxidant factor known as marinobufagenin, may boost oxidative stress in the insulin-production pancreatic beta cells, and that this may help to precipitate the onset of diabetes by impairing beta cell function.

  25. Nutraceutical Strategies for Controlling the Secretory Phenotype Associated with Cellular Senescence

    As we get older, our body’s harbor an increased number of “senescent” cells no longer capable of dividing. These cells tend to secrete pro-inflammatory hormones which may contribute to the cancer induction and inflammation linked to the aging process. This essay suggests that glucosamine and other supplements may have potential for controlling the pro-inflammatory impact of these senescent cells.

  26. Diet/Lifestyle Strategies for Preventing Benign Prostatic Hyperplasia

    Cites evidence that this syndrome, often thought to be an inevitable concomitant of aging, was in fact once rare in elderly East Asians. Suggests that low growth factor activities associated with plant-based diets and a low-insulin lifestyle may have been largely responsible for this, and also proposes a role for soy isoflavones, spirulina, and berberine in prevention of BPH.

  27. Nutraceutical Strategies for Preserving Cartilage in Osteoarthritis

    The loss of cartilage associated the osteoarthritis reflects an inflammatory process that promotes degradation of cartilage proteins. This essay proposes that a number of nutraceuticals – spirulina, phase 2 inducers, berberine, glucosamine, vitamin D, and fish oil – have potential for intervening in the pro-inflammatory signaling pathways that promote cartilage loss.

  28. Proposal: A Pre-Meal Beet Juice “Cocktail” for Prevention and Control of Type 2 Diabetes

    Dietary nitrate, richly supplied by green leafy vegetables and beet juice, aids production of protective nitric oxide, and is now thought to reduce risk for heart attack and stroke. This essay suggests that dietary nitrate may also decrease diabetes risk by aiding insulin sensitivity, and proposes a beet juice “cocktail” which may work in complementary ways to reduce this risk.

  29. Dietary Nitrate May Aid Prevention of Neovascular Age-related Macular Degeneration by Suppressing the Transcriptional Activity of Hypoxia-Inducible Factor-1 and Aiding Choroidal Perfusion

    A high daily intake of spinach or collard greens has been linked to a considerable decrease in risk for age-related macular degeneration, chief cause of partial blindness in the elderly. Although the lutein content of these vegetables is thought to be largely responsible for this protection, this essay proposes that the nitrate content of these vegetables may also play a role in this protection, and suggests a mechanism that might account for this.

  30. Dietary Nitrate and Reductive Polyphenols May Potentiate the Vascular Benefit and Alleviate the Ulcerative Risk of Low-Dose Aspirin

    Low-dose aspirin has tremendous protective potential; not only can it reduce risk for heart attack and stroke, but more recent evidence suggests it may notably reduce cancer mortality during long-term use. Nonetheless, it also sometimes provokes GI ulceration and bleeding that in some cases can be life-threatening. This essay proposes that joint consumption of dietary nitrate and of certain natural polyphenols, in foods or supplements, may decrease this bleeding risk by generating protective nitric oxide in the gastric lining – making low-dose aspirin more uniformly protective.

  31. Zinc and Multi-Mineral Supplementation Should Mitigate the Pathogenic Impact of Cadmium Exposure

    High-normal cadmium levels have recently emerged as a risk factor for vascular disease, cancer, osteoporosis, kidney disease, diabetes, and total mortality. This essay proposes that supplementing meals with zinc and multi-minerals can be expected to impede the absorption of dietary cadmium, while making the cadmium already in the body less dangerous via induction of the protective cadmium-binding protein metallothionein. Antioxidant strategies may also lessen the pathogenic impact of cadmium.

  32. Bilirubin and Phycocyanobilin vs. the Fifteen Leading Causes of Death

    Recent studies demonstrate that the natural metabolite bilirubin functions physiologically to inhibit a primary source of the oxidative stress driving many health disorders – NADPH oxidase. A phytonutrient known as phycocyanobilin, richly supplied by spirulina, is a chemical relative of bilirubin, and shares its antioxidant activity. This essay proposes that spirulina (or phycocyanobilin) may have the potential to aid prevention or treatment of 12 of the 15 leading causes of death in the U.S. today.

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