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September 1998

Vitamin B12

New studies show that supplemental vitamin B12 absorbs better through the stomach than was previously thought. These reports, published in mainstream medical journals, show that orally administered vitamin B12 supplements are effectively absorbed by more than 99 percent of humans (B12 is difficult to absorb from the digestive tract only when it is tightly bound to food). Vitamin B12 plays a role in many enzymatic processes required to maintain good health, and works synergistically with folic acid and TMG to enhance DNA methylation and reduce toxic homocysteine in the blood. Also, elderly people can suffer from severe neurological impairment if they are deficient in vitamin B12.

The 1998 Life Extension Mix formula contains five times more vitamin B12 than in the past. In addition to cyanocobalamin, another form of vitamin B12 called hydroxyl cobalamin has been added that works via different enzymatic pathways.


Biotin is a B-complex vitamin that provides health benefits ranging from the control of blood sugar levels to the improved appearance of hair and nails. Biotin has been shown to ameliorate abnormal glucose metabolism in diabetics by enhancing the activity of the biotin-dependent enzyme required for the promotion of proper glucose utilization.

The potency of biotin in the 1998 Life Extension Mix formula has been tripled.


Vitamin B6 readily converts to its enzymatically active form (pyridoxal-5-phosphate) in most people. Some people do not convert vitamin B6 as well as others, so the 1998 formula includes enough biologically available pyridoxal-5-phosphate to ensure that no one taking Life Extension Mix will suffer from a "sub-clinical" (that is, early and not easily detected) vitamin B6 deficiency. The total amount of vitamin B6 in the formula has been reduced to guard against B6-induced peripheral neuropathy. While the amount of B6 in previous versions of Life Extension Mix would not cause toxicity, some people take additional vitamin B6 in other nutrient formulas, and we want to make sure that no one inadvertently takes too much B6 over an extended period of time.


It is well known that PABA absorbs dangerous ultraviolet B (UVB) radiation. However, PABA also protects against ultraviolet A (UVA) damage via a unique free radical-scavenging ability. Thus, PABA is useful in protecting against photocarcinogenesis by wide-range UV radiation. PABA also inhibits the formation of thrombin-induced thromboxane (a potent inducer of platelet aggregation and a constrictor of arterial smooth muscle) in human platelets, and thus reduces the risk of abnormal blood clot formation, blocking the flow of blood (thrombosis).

Four times more PABA has been added to the 1998 Life Extension Mix formula.

Ginger Extract

The leading cause of disability and death in the Western world is thrombosis. Most heart attacks and strokes are caused by thrombotic events. Many of the nutrients in Life Extension Mix have proven anti-thrombotic properties. Ginger, consumed worldwide as a spice and flavoring agent, possesses antioxidative and anti-inflammatory properties as an extract, and may also be one of the most effective nutrients in preventing thrombosis. In one study, a single dose of 10 grams of powdered ginger produced a significant reduction in platelet aggregation.

Other findings suggest that ginger could be an effective anti-emetic (preventing nausea and vomiting) for patients on cancer chemotherapy. Further, there is evidence that ginger protects against skin tumor promotion. In a mouse study, the topical application of ginger extract protected against the genesis and spread of skin tumors.

We've added a pharmaceutical ginger extract to the new Life Extension Mix to provide additional protection against thrombosis, inflammation and other pathological conditions.


Dr. Linus Pauling's last great work was to show that specific components in the blood called apolipoproteins are involved in atherosclerosis and valvular stenosis. Dr. Pauling showed that vitamin C and lysine can protect against apolipoprotein-induced vascular disease. The 1998 Life Extension Mix formula contains the amount of lysine (500 mg) found in most lysine supplements. Those with valvular stenosis (narrowing) or severe atherosclerosis should take additional lysine under the care of a physician.


Magnesium deficiency is a prime culprit in the epidemic of arterial disease that plagues the Western world. Foundation members have obtained high doses of magnesium ever since Life Extension Mix was introduced. Different forms of magnesium have shown other beneficial effects at the cellular level in addition to vascular protection. The new Life Extension Mix contains an advanced magnesium complex consisting of magnesium arginate, magnesium taurinate and magnesium glycinate to provide magnesium to different parts of the cell.

Natural Vitamin E

The 1998 Life Extension Mix contains 400 IU of d-alpha tocopheryl succinate, a natural form of vitamin E that appears to protect against cancer better than other forms of vitamin E. The previous formula only provided 250 IU of d-alpha tocopheryl succinate. The total amount of natural and synthetic vitamin E in the new formula is now 500 IU per daily dose.

In order to make room for all these nutrients, calcium has been removed from the formula, except for the small amount found naturally in compounds such as calcium ascorbate and calcium pyruvate. Life Extension Mix has never been a high source of calcium, which is required in high doses by women over 40. Women seeking to maintain bone density should take Mineral Formula For Women. Men can obtain supplemental calcium and additional magnesium in Mineral Formula For Men.

Also reduced in the new formula is the amount of vitamin B1, because the higher amount of NAC provides similar antioxidant protection. And the amount of vitamin B6 has been reduced because, in addition to protecting against accidental overdosing, the consensus of scientific opinion is that 100 mg a day of B6 is adequate for most people. However, as noted above, the active form of vitamin B6 (pyridoxal-5-phosphate) has been added to ensure that anyone using Life Extension Mix will obtain adequate amounts of this important vitamin.

While the added ingredients in the new Life Extension Mix have caused its price to increase, customer will still be paying the lowest "cost per milligram" price for the pharmaceutical-grade nutrients found in every bottle of this unique formula.

Further Reading

NAC (N-acetylcysteine)

  • Regulation of scavenger receptor expression in smooth muscle cells by protein kinase C: a role for oxidative stress, Mietus Snyder M; Friera A; Glass CK; Pitas RE, Arterioscler Thromb Vasc Biol, 1997 May, 17:5, 969-78
  • N-acetyl cysteine attenuates acute lung injury in the rat, CJ Davreux, I Soric, AB Nathens, et al., Shock, 1997, Vol 8, Iss 6, pp 432-438
  • The intrabronchial microbial flora in chronic bronchitis patients: a target for N-acetylcysteine therapy? Eur Respir J (DENMARK) Jan 1994, 7 (1) p94-101
  • The influence of n-acetylcysteine on chemiluminescence of granulocytes in peripheral blood of patients with chronic bronchitis, Pneumonol Alergol Pol (POLAND) 1993, 61 (11-12)
  • Protection by N-acetylcysteine of the histopathological and cytogenetical damage produced by exposure of rats to cigarette smoke. Cancer Lett (NETHERLANDS) Jun 15 1992, 64 (2) p123-31
  • N-Acetylcysteine for Lung Cancer Prevention, Nico Chest May 1995;107(5):1437-1441.
  • Outpatient N-acetylcysteine treatment for acetaminophen poisoning: An ethical dilemma or a new financial mandate? Veterinary and Human Toxicology (USA), 1996, 38/3 (222-224)
  • Induction of HSP 32 gene in hypoxic cardiomyocytes is attenuated by treatment with N-acetyl-L-cysteine, DR Borger, DA Essig, American Journal of Physiology-Heart and Circulatory Physiology, 1998, Vol 43, Iss 3, pp H965-H973
  • Neutrophil function and glutathione-peroxidase (GSH-px) activity in healthy individuals after treatment with N-acetyl-L-cysteine, T Urban, B Akerlund, C Jarstrand, et al., Biomedicine & Pharmacotherapy, 1997, Vol 51, Iss 9, pp 388-390


  • A high biotin diet improves the impaired glucose tolerance of long-term spontaneously hyperglycemic rats with non-insulin-dependent diabetes mellitus, Zhang H.; Osada K.; Maebashi M.; Ito M.; et al., Journal of Nutritional Science and Vitaminology (Japan), 1996, 42/6 (517-526)
  • Oral glucose tolerance test after high-dose I.V. biotin administration in normoglucemic hemodialysis patients, Koutsikos D.; Fourtounas C.; Kapetanaki A.; et al., Renal Failure (USA), 1996, 18/1 (131-137)
  • Biotin supplementation improves glucose and insulin tolerances in genetically diabetic KK mice, Reddi A.; DeAngelis B.; Frank O.; et al., Life Sci. (USA) , 1988, 42/13 (1323-1330)
  • Pyridoxal-5-phosphate Platelet adhesion onto artificial surfaces: Inhibition by benzamidine, pentamidine, and pyridoxal-5-phosphate as demonstrated by flow cytometric quantification of platelet adhesion to microspheres, CH Gemmell, Journal of Laboratory and Clinical Medicine, 1998, Vol 131, Iss 1, pp 84-92


  • Antiemetic efficacy of ginger (Zingiber officinale) against cisplatin-induced emesis in dogs. J Ethnopharmacol, 1997 Jul, 57:2, 93-6
  • Anxiolytic-like effect of combined extracts of Zingiber officinale and ginkgo biloba in the elevated plus-maze. Pharmacol Biochem Behav, 1996 Feb, 53:2, 271-5
  • New curcuminoids isolated from Zingiber cassumunar protect cells suffering from oxidative stress: a flow-cytometric study using rat thymocytes and H2O2, Nagano T; Oyama Y; Kajita N; et al., Jpn J Pharmacol, 1997 Dec, 75:4, 363-70
  • Inhibition of tumor promotion in SENCAR mouse skin by ethanol extract of Zingiber officinale rhizome. Katiyar SK; Agarwal R; Mukhtar H, Cancer Res, 1996 Mar, 56:5, 1023-30
  • Effect of ginger (Zingiber officinale Rosc.) and fenugreek (Trigonella foenumgraecum L.) on blood lipids, blood sugar and platelet aggregation in patients with coronary artery disease.
  • Bordia A; Verma SK; Srivastava KC, Prostaglandins Leukot Essent Fatty Acids, 1997 May, 56:5, 379-84

Grape Seed-Skin Extract

  • Oedema Inhibiting Effect Of Procyanidin, G. Blazsó and M. Gábor, Act Physiologica Academiae Hungaricae, Tomus 56 (2) pp. 235-240 February 1, 1980
  • Protective Action Of Wine Against Gastric Ulcers, J Masquelier
  • Recherches subventionnées par la Conseil Interprofessional du vin de Bordeaux
  • Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science, 1997 Jan 10, 275:5297, 218-20
  • Wines and grape juices as modulators of platelet aggregation in healthy human subjects. Pace Asciak CR; Rounova O; Hahn SE; et al., Clin Chim Acta, 1996 Mar, 246:1-2, 163-82
  • Antiplatelet activity of cis-resveratrol. Bertelli AA; Giovannini L; Bernini W; et al., Drugs Exp Clin Res, 1996, 22:2, 61-3
  • Vasorelaxing activity of resveratrol and quercetin in isolated rat aorta. Chen CK; Pace Asciak CR Gen Pharmacol, 1996 Mar, 27:2, 363-6
  • Amelioration of oxidative stress by antioxidants and resveratrol in PC12 cells. Chanvitayapongs S; Draczynska Lusiak B; Sun AY, Neuroreport, 1997 Apr, 8:6, 1499-502
  • Resveratrol inhibits metal ion-dependent and independent peroxidation of porcine low-density lipoproteins. Belguendouz L; Fremont L; Linard A, Biochem Pharmacol, 1997 May, 53:9, 1347-55
  • Resveratrol, a remarkable inhibitor of ribonucleotide reductase. Fontecave M; Lepoivre M; Elleingand E; Gerez C; Guittet O, FEBS Lett, 1998 Jan, 421:3, 277-9
  • Isolation, synthesis, and antiplatelet aggregation activity of resveratrol 3-O-beta-D-glucopyranoside and related compounds. Orsini F; Pelizzoni F; Verotta L; et al., J Nat Prod, 1997 Nov, 60:11, 1082-7
  • Alcohol, ischemic heart disease, and the French paradox. Constant J, Coron Artery Dis, 1997 Oct, 8:10, 645-9


  • Biochemical and clinical response to hydroxocobalamin versus cyanocobalamin treatment in patients with methylmalonic acidemia and homocystinuria (CblC), HC Andersson, E Shapira, Journal of Pediatrics, 1998, Vol 132, Iss 1, pp 121-124
  • Nasal absorption of hydroxocobalamin in healthy elderly adults, DZB vanAsselt, FWHM Merkus, FGM Russel, et al., British Journal of Clinical Pharmacology, 1998, Vol 45, Iss 1, pp 83-86


  • Reversible model of magnesium depletion induced by systemic kainic acid injection in magnesium-deficient rats: I--Comparative study of various magnesium salts. Magnes Res, 1996 Dec, 9:4, 281-91
  • Relationship of calcium, magnesium, zinc and copper concentrations in the arterial wall and serum in atherosclerosis obliterans and aneurysm, M Iskra, J Patelski, W Majewski, Journal of Trace Elements in Medicine and Biology, 1997, Vol 11, Iss 4, pp 248-252
  • Differential effects of extracellular Mg2+ on thrombin-induced and capacitative Ca2+ entry in human coronary arterial endothelial cells, M Yoshimura, T Oshima, H Matsuura, et al., Arteriosclerosis Thrombosis and Vascular Biology, 1997, Vol 17, Iss 11, pp 3356-3361


  • Mechanisms of the regulation of thioredoxin reductase activity in cancer cells by the chemopreventive agent selenium, A Gallegos, M Berggren, JR Gasdaska, G Powis, Cancer Research, 1997, Vol 57, Iss 21, pp 4965-4970


  • Prevention of CCL4-induced liver cirrhosis by silymarin. Fundam Clin Pharmacol (1989) 3(3):183-91
  • Free radicals in tissue damage in liver diseases and therapeutic approach. Tokai J Exp Clin Med (1986) 11 Suppl:121-34
  • Reliable phytotherapy in chronic liver diseases, Therapiewoche (Germany), 1996, 46/17 (916+ 918-919)
  • A flavonoid antioxidant, silymarin, inhibits activation of erbB1 signaling and induces cyclin-dependent kinase inhibitors, G1 arrest, and anticarcinogenic effects in human prostate carcinoma DU145 cells. Zi X; Grasso AW; Kung HJ; Agarwal R, Cancer Res, 1998 May, 58:9, 1920-9
  • Anticarcinogenic effect of a flavonoid antioxidant, silymarin, in human breast cancer cells MDA-MB 468: induction of G1 arrest through an increase in Cip1/p21 concomitant with a decrease in kinase activity of cyclin-dependent kinases and associated cyclins. Zi X; Feyes DK; Agarwal R, Clin Cancer Res, 1998 Apr, 4:4, 1055-64
  • Silymarin inhibits the development of diet-induced hypercholesterolemia in rats. Krecman V; Skottová N; Walterová et al., Planta Med, 1998 Mar, 64:2, 138-42
  • Milk thistle (Silybum marianum) for the therapy of liver disease. Flora K; Hahn M; Rosen H; Benner K, Am J Gastroenterol, 1998 Feb, 93:2, 139-43
  • Novel cancer chemopreventive effects of a flavonoid antioxidant silymarin: inhibition of mRNA expression of an endogenous tumor promoter TNF alpha. Zi X; Mukhtar H; Agarwal R, Biochem Biophys Res Commun, 1997 Oct, 239:1, 334-9
  • Long-term (12 months) treatment with an anti-oxidant drug (silymarin) is effective on hyperinsulinemia, exogenous insulin need and malondialdehyde levels in cirrhotic diabetic patients. Velussi M; Cernigoi AM; De Monte A; et al., J Hepatol, 1997 Apr, 26:4, 871-9
  • Protective effects of silymarin against photocarcinogenesis in a mouse skin model. Katiyar SK; Korman NJ; Mukhtar H; Agarwal R, J Natl Cancer Inst, 1997 Apr, 89:8, 556-66
  • Silymarin retards collagen accumulation in early and advanced biliary fibrosis secondary to complete bile duct obliteration in rats. Boigk G; Stroedter L; Herbst H, et al., Hepatology, 1997 Sep, 26:3, 643-9
  • Silibinin, a plant extract with antioxidant and membrane stabilizing properties, protects exocrine pancreas from cyclosporin A toxicity. von Schönfeld J; Weisbrod B; Müller MK, Cell Mol Life Sci, 1997 Dec, 53:11-12, 917-20


  • UVA-potentiated damage to calf thymus DNA by Fenton reaction system and protection by para-aminobenzoic acid. Photochem Photobiol, 1996 Mar, 63:3, 286-91
  • p-Aminobenzoic acid, but not its metabolite p-acetamidobenzoic acid, inhibits thrombin induced thromboxane formation in human platelets in a non NSAID like manner. Thromb Res, 1997 Apr 15, 86:2, 127-40


  • Brain protein and alpha-ketoglutarate dehydrogenase complex activity in Alzheimer's disease. Mastrogiacoma F; Lindsay JG; Bettendorff L; et al., Ann Neurol, 1996 May, 39:5, 592-8
  • Deficient activity of the alpha-ketoglutarate dehydrogenase complex (KGDHC) has been documented in Alzheimer disease (AD) brain and fibroblasts. Dev Neurosci, 1996, 18:5-6, 499-504 Enteral supplementation with ornithine alpha ketoglutarate improves the early adaptive response to resection. Gut, 1997 Jan, 40:1, 67-72
  • Ornithine alpha-ketoglutarate metabolism after enteral administration in burn patients: bolus compared with continuous infusion. Am J Clin Nutr, 1997 Feb, 65:2, 512-8
  • Ornithine alpha-ketoglutarate modulates tissue protein metabolism in burn-injured rats, J LeBoucher, C Obled, MC Farges, L Cynober, American Journal of Physiology-Endocrinology and Metabolism, 1997, Vol 36, Iss 3, pp E557-E563
  • Alpha-Ketoglutarate application in hemodialysis patients improves amino acid metabolism. Riedel E; Nündel M; Hampl H, Nephron, 1996, 74:2, 261-5
  • Ornithine-alpha-ketoglutarate (OKG) supplementation is more effective than its component salts in traumatized rats. Jeevanandam M; Holaday NJ; Petersen SR, J Nutr, 1996 Sep, 126:9, 2141-50


  • Protection of cytochrome c oxidase against cyanide inhibition by pyruvate and alpha-ketoglutarate: effect of aeration in vitro. Delhumeau G; Cruz Mendoza AM; Gomez Lojero C Toxicol Appl Pharmacol, 1994 Jun, 126:2, 345-51
  • Specific replacements of pyruvate for trophic support of central and peripheral nervous system neurons. Facci L; Skaper SD; Varon S J Neurochem, 1985 Sep, 45:3, 926-34
  • Role of pyruvate carboxylase in facilitation of synthesis of glutamate and glutamine in cultured astrocytes. Gamberino WC; Berkich DA; Lynch CJ; et al., J Neurochem, 1997 Dec, 69:6, 2312-25
  • Formation of advanced glycation end (AGE) products in diabetes: prevention by pyruvate and alpha-keto glutarate. Varma SD; Devamanoharan PS; Ali AH Mol Cell Biochem, 1997 Jun, 171:1-2, 23-8
  • Pyruvate reverses fatty-acid-induced impairment of mechanical recovery of ventricular function of guinea pig hearts and reverses calcium overload after hypothermia. show that these unfavourable effects of fatty acids can be overcome by an exogenous supply of pyruvate. Cardiovasc Res, 1997 Feb, 33:2, 370-7
  • Effects of aging on the activities of pyruvate dehydrogenase complex and its kinase in rat heart. Life Sci, 1997, 60:25, 2309-14
  • Pyruvate reduces anoxic injury and free radical formation in perfused rat hepatocytes. Am J Physiol, 1996 Mar, 270:3 Pt 1, G535-40


  • Modification of apolipoprotein(a) lysine binding site reduces atherosclerosis in transgenic mice. Boonmark NW; Lou XJ; Yang ZJ; et al., J Clin Invest, 1997 Aug, 100:3, 558-64
  • Lysine-binding heterogeneity of Lp(a): consequences for fibrin binding and inhibition of plasminogen activation. Bas Leerink C; Duif PF; Gimpel JA; et al., Thromb Haemost, 1992 Aug 3, 68:2, 185-8


  • In vitro anticancer activity of fruit extracts from Vaccinium species. Bomser J; Madhavi DL; Singletary K; et al., Planta Med, 1996 Jun, 62:3, 212-6
  • Cranberries: chemical composition, nutritional and medicinal properties] Zaitsev AN; Sorokina EIu; Aksiuk IN; Levin LG, Vopr Pitan, 1997, :2, 38-40


  • Effect of betaine on HSP70 expression and cell survival during adaptation to osmotic stress. Petronini PG; De Angelis EM; Borghetti AF; Wheeler KP, Biochem J, 1993 Jul 15, 293 ( Pt 2):, 553-8
  • Effect of trimethylglycine on lipid metabolism in experimental atherosclerosis in rabbits, Panteleimonova TN; Zapadniuk VI, Farmakol Toksikol, 1983 Jul-Aug, 46:4, 83-5
  • Cholagogic effect of trimethylglycine in normal animals of different ages and in experimental atherosclerosis, Zapadniuk VI; Panteleimonova TN Biull Eksp Biol Med, 1987 Jul, 104:7, 30-2
  • Corrective effect of trimethylglycine on the nicotinamide coenzyme and adenine nucleotide content of the tissues in experimental atherosclerosis, Zapadniuk VI; Chekman IS; Panteleimonova TN; Tumanov VA Farmakol Toksikol, 1986 Jul-Aug, 49:4, 71-3
  • Homocystinuria due to cystathionine beta-synthase deficiency--the effects of betaine treatment in pyridoxine-responsive patients. Wilcken DE; Dudman NP; Tyrrell PA Metabolism, 1985 Dec, 34:12, 1115-21
  • Betaine, metabolic by-product or vital methylating agent? Barak AJ; Tuma DJ Life Sci, 1983 Feb 14, 32:7, 771-4
  • Transmethylation of homocysteine to methionine: efficiency in the rat and chick. Baker DH; Czarnecki GL J Nutr, 1985 Oct, 115:10, 1291-9
  • Altered methionine metabolism and transmethylation in cancer. Hoffman RM Anticancer Res, 1985 Jan-Feb, 5:1, 1-30
  • Methionine kinetics in adult men: effects of dietary betaine on L-[2H3-methyl-1-13C]methionine. Storch KJ; Wagner DA; Young VR Am J Clin Nutr, 1991 Aug, 54:2, 386-94
  • The influence of dietary folate and methionine on the metabolic disposition of endotoxic homocysteine. Lucock MD; Daskalakis IG; Wild J; et al., Biochem Mol Med, 1996 Dec, 59:2, 104-11
  • Methionine metabolism and cancer. van der Westhuyzen J Nutr Cancer, 1985, 7:3, 179-83


  • Dl-alpha-tocopherol, a potent inhibitor of phorbol ester induced shape change of erythro- and megakaryoblastic leukemia cells M Steiner, W Li, JM Ciaramella, et al., Journal of Cellular Physiology, 1997, Vol 172, Iss 3, pp 351-360
  • Vitamin E succinate inhibits proliferation and migration of retinal pigment epithelial cells in vitro: therapeutic implication for proliferative vitreoretinopathy Sakamoto T; Hinton DR; Kimura H; et al., Graefes Arch Clin Exp Ophthalmol, 1996 Mar, 234:3, 186-92
  • Naphthalene-induced oxidative stress in rats and the protective effects of vitamin E succinate. Vuchetich PJ; Bagchi D; Bagchi M; et al., Free Radic Biol Med, 1996, 21:5, 577-90
  • Antiproliferative effect of intravitreal alpha-tocopherol and alpha-tocopheryl-acid-succinate in a rabbit model of PVR. Larrosa JM; Veloso AA Jr; Leong FL; Refojo MF Curr Eye Res, 1997 Oct, 16:10, 1030-5
  • alpha-Tocopheryl succinate inhibits monocytic cell adhesion to endothelial cells by suppressing NF-kappa B mobilization. Erl W; Weber C; Wardemann C; Weber PC Am J Physiol, 1997 Aug, 273:2 Pt 2, H634-40
  • Modulation of TCDD-induced fetotoxicity and oxidative stress in embryonic and placental tissues of C57BL/6J mice by vitamin E succinate and ellagic acid. Hassoun EA; Walter AC; Alsharif NZ; Stohs SJ Toxicology, 1997 Dec, 124:1, 27-37
  • Effect of alpha-tocopherol succinate on free radical and lipid peroxidation levels in BL6 melanoma cells. Ottino P; Duncan JR Free Radic Biol Med, 1997, 22:7, 1145-51
  • Inhibitory effect of vitamin E succinate on the proliferation of cultured bovine choroidal endothelial cells] Sakamoto T; Oshima Y; Ishibashi T; Inomata H Nippon Ganka Gakkai Zasshi, 1996 Oct, 100:10, 777-82