Category Archives: aspirin

UPDATE: FOR MILDER PAIN, WHY USE NSAIDS (LET ALONE DICLOFENAC) OTHER THAN PARACETAMOL -ACETAMINOPHEN?

update

Aspirin,  paracetamol, other NSAIDs,  and codeine  in periodic conservative analgesic use have  not been reported to cause hypoglycemia eg a few gm a day solo or in combination  in well adults-  despite  deliberate overdose of these being  notorious for causing fatal bleeding or  liver failure with hypoglycemia, or respiratory failure.

But increasingly tramadol is incriminated in dangerous hypoglycemia: Tramadol Use and the Risk of Hospitalization for Hypoglycemia in Patients With Noncancer Pain Fournier, Suissa, eaJAMA Intern Med.December      Tramadol is an increasingly widely used  weak opioid analgesic , associated with adverse events of hypoglycemia.  Analysis  in United Kingdom Clinical Practice of treatnent with tramadol or codeine for noncancer pain between 1998 and 2012  included 334 034 patients, of whom 1105 were hospitalized for hypoglycemia during follow-up (incidence, 0.7 per 1000 per year) and matched to 11 019 controls. Compared with codeine, tramadol  associated with  increased risk of hospitalization for hypoglycemia  in the first 30 days of use (OR, 2.61 [95% CI, 1.61-4.23]). This 30-day increased risk was confirmed in the case-crossover analyses (OR, 3.80 [95% CI, 2.64-5.47]). Conclusions  tramadol (in contrst to codeine), TRIPLED risk of hypoglycemia requiring hospitalization. Additional studies are needed to confirm this rare but potentially fatal adverse event.

update 4 March 2013  BAN DICLOFENAC?  four years on, another call comes  for the virtual banning of diclofenac, from no less than the Canadian Medical Association Journal , based on a new metanalysis of NSAID risks by University  Toronto’s McGettigan and Henry .

As this column has long pointed out, diclofenac is apparently still the only NSAID that can kill suddenly without warning.  There are many far safer alternatives eg naproxen, ibrufen; and no compelling clinical evidence or reason to use it let alone cox2 inhibitors  except false beliefs and heavy marketing.

So as this columnist concluded in 2009,  it is blatant fraud, negligence and potential indefensible homicide  to continue recommending  let alone  using diclofenac simply for profiteering.

21June 2009 It is 4 months since this column last addressed nonsteroidal anti-inflammatory drugs NSAIDs.

A new study (from USA, UK and Canada – Ray 2009) of NSAIDs  claims that in those with ischemic heart disease, the popular NSAIDS -diclofenac, ibuprofen or rofecoxib(Vioxx) – increased serious heart disease/ death by about 50-67% compared to nonusers; whereas naproxen over some 111000 patient years of use gives no significant risk or benefit.

A new study from Denmark (Fosbol 2009) this year looked at a million healthy individuals with no hospital admissions or selected therapy. Compared to no NSAID use, ibruprofen and naproxen gave no added risk of death/ myocardial infarction; diclofenac gave 67% increased risks, and the two coxibs (rofecoxib Vioxx; celecoxib Celebrex)  increased risk 100%.

So we are led to believe that naproxen or ibuprofen is the NSAID  mild-to-moderate analgesic  of choice. Naturally the American Colleges and academia – who represent the Disease Industry, not patients- recommend yet other potentially toxic drugs- like  the magical proton pump inhibitors- to counteract the adverse NSAIDS..

But is this just a myopic view beloved of big pharma, to promote their snake oils.?

Another new study from Denmark (Gislason 2009) of 110 000 patients after admission for heart failure in the 12 years 1994-2005, showed that 57% died; 9000 (8%) were rehospitalized with acute heart attack  and 40 000 (38%) were rehospitalized with heart failure. Thus heart failure in a well-nourished population has a poor prognosis. In 36 000 who had used NSAIDs compared to non-users, risk of death was doubled on  diclofenac; increased~67% on  (rofe-or cele)coxibs; and was  significantly increased 22-31% by all other NSAIDs including naproxen and ibruprofen.

It is common cause after 20 years that injected diclofenac is the only NSAID that can unpredictably cause sudden death. So it’s administration risks culpable homicide when it is totally unwarranted. No cases of sudden death from any oral NSAID   including aspirin appear on Medline, apart perhaps from the risk of hyperacute asthma (Asamoto 1999).

But what of gastrointestinal bleeding  risks of NSAIDS? a 2007 study in Japan (Yajima) scoped all orthopaedic patients who took NSAIDs for more than 4 wks: oral diclofenac increased risk of erosive gastric lesions sixfold. A new review from Seattle (Schlansky 2009) refers to Helicobacter synergism in all NSAID use.

WHAT IS THE NEED FOR NSAIDS? The Wikipedia entry on NSAIDs  sums it up: it has almost four times as much text on the numerous  adverse effects of NSAIDs as on their uses- in fact the  article does not discuss the advantages of NSAIDS as analgesics; in fact it states plainly  that alone  just  “their gastrointestinal effects  are estimated to result in 103,000 hospitalizations and 16,500 deaths per year in the United States”.

All designer drugs are dangerous in overdose. Without overdose, paracetamol has no risk – and the Wikipedia entry thereon is balanced and highly favourable even for infants. We know well that paracetamol- a fatal liver toxin in overdose- should not be marketed without a built-in simple liver (and antineuritic) protective of  eg (carbo-or N-acetyl-)cysteine, alphalipoic acid and vitamin BCo.  But the Disease – Big Pharma Industry is not interested in prevention- Only Disease Pays. And Regulators, lobbyists and legislators  protect their source of work and income- the Drug Industry.

Fish oil (EPA+DHA) is probably  the most beneficial NSAID supplement we have (- perhaps ahead of other front-runners like vitamins C, D, magnesium and CoQ10-) halving all sudden deaths, and reducing by at least a third all major chronic degenerative diseases from CVD to diabetes, arthritis, learning, depression, behaviour disorders. Industry wont pay for head-on comparative trials. But the trial evidence suggests that fish oil and oral EDTA have better risk-benefit than aspirin and other antiplatelet agents, NSAIDs and warfarin.

We know that for moderate trauma and small – medium (even knee) joint pain/  contusions, self-massage with any natural NSAID like arnica or wintergreen is all that is needed, combined if necessary orally with up to 3 to 4gm paracetamol /day +- if needed a little codeine.   Prior 2002 found no significant difference in pain relief between paracetamol and naproxen in tension headache.

For more serious pain,  short of strong opioids, there is in fact no overall trial evidence that weak opioids or NSAIDs are better than eg hypnotherapy, or acupuncture,  or judicious paracetamol; to which latter if necessary a little codeine can be added as step-up analgesia. The latter  agents have none of the deadly risk of NSAIDs. Amadio 1984 showed that of Peripherally Acting Analgesics: ” paracetamol at up to 4 g per day compares favorably in analgesic potency to aspirin and other NSAIDs, and  should be considered the treatment of choice for mild-to-moderate pain”.  Skovlund 1991 showed no significant difference between naproxen and paracetamol in postpartum uterine spasms.

Six RCTs – five in mostly European peoples and one in Hong Kong- found paracetamol equal to diclofenac (Voltaren) – March 1994 in arthritis; Brevik 1999 and Kubitzek 2003 in dental surgery; Hoogewijs 2000 and Woo 2006 after trauma; and Munishankar 2008 after Caesarian section.  In a Cochrane analysis 2003, Towheed showed that in the one placebo-controlled RCT in osteoarthritis, paracetamol was clearly superior to placebo with a similar safety profile. And the general principle of therapy applies, that if required, combination of analgesics from different groups is better than single drug therapy. But given the many potentially fatal risks of the NSAIDs – compared to paracetamol, opioids and if indicated  aspirin –  there is no compelling reason to add NSAIDs  for pain.

We know that it is negligent to initially sentence people with  spontaneous mild-moderate head/neck/backache or tendonitis at the shoulder, elbow, knee etc to bedrest, NSAIDS, opioids or referral for xrays, scans or surgery. 95% will settle rapidly with reassurance, posture instruction and simple topicals and paracetamol analgesia. Otherwise most pain will disappear with firm reassurance with brief simple laying on of hands eg massage and traction with gentle rotational manipulation and instruction in auto-reinforcement –  pressure point eg earlobe pressure, or acupuncture, or hypnosis. And most of the remainder resolve quickly with  simple targeted injection with a little local anaesthetic plus depot steroid.

And we know that with judicious use, topical corticosteroid injection – never mind judicious brief systemic steroid (corticosteroid, calciferol, testosterone) has little or no risk and far greater target and multisystemic benefit than NSAIDs; and for chronic conditions, like fish oil at least address the underlying pathogenic mechanisms/causes- whereas NSAIDs and paracetamol ignore these.

Is drug-speeded resolution of inflammation essential and beneficial except for the drug vendor? A careful RCT by Bradley ea from Indiana University in 1992 observed that “joint tenderness and swelling, presumptive evidence of synovitis, may not be a priori indications for use of an antiinflammatory drug, or predict greater responsiveness to treatment with an antiinflammatory drug than to a pure analgesic, in symptomatic treatment of patients with knee osteoarthritis”.

So why are synthetic  NSAIDs and especially the Coxibs  still used? Why do academics and Regulators still allow, promote  them for  routine use, other than to profit Big Pharma, and cause perhaps a quarter million deaths a year globally?

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VALUE OF STROKE CLOTBUSTERS QUESTIONED

Thrombolysis review controversy

Sarah Colyer  in the Australian Jnl of Medicine MJA  Monday, 13 October, 2014 reviews the raging argument:   “LEADING neurologists have condemned an Australasian College for Emergency Medicine decision to fund its own analysis of thrombolysis for acute stroke, which the college claims would be free of the conflicts of interest that plague existing guidance on the treatment.The Australasian College for Emergency Medicine (ACEM) is inviting proposals for consultants to analyse the published literature on thrombolysis in acute ischaemic stroke, which it has refused to endorse as a standard of care. (1)

Professor Yusuf Nagree, chair of the ACEM Scientific Committee, said unlike reviews published to date, its analysis would be “uniquely independent”.

“We are trying to find researchers who have no preconceived views or biases”, he told MJA InSight. An expert advisory panel would also be established to support the project, including an emergency physician, neurologist, GP, public health expert and lay person.

A Cochrane review published earlier this year found thrombolytic therapy significantly reduced death and dependency rates at 3‒6 months after stroke, and that this overall benefit was apparent despite an increase in symptomatic intracranial haemorrhage and deaths at 7‒10 days.(2)

While we await sight of the full Cochrane  paper, it is noteworthy that the abstract fails to give the absolute numbers.

Cochrane Database Syst Rev. 2014 Jul 29;7:CD000213. doi: 10.1002/14651858.CD000213.pub3.

Thrombolysis for acute ischaemic stroke.  Wardlaw JM1, Murray V, Berge E, del Zoppo GJ.:

“Most strokes are due to blockage of an artery in the brain by a blood clot. Prompt treatment with thrombolytic drugs can restore blood flow before major brain damage has occurred and improve recovery after stroke in some people. Thrombolytic drugs, however, can also cause serious bleeding in the brain, which can be fatal. One drug, recombinant tissue plasminogen activator (rt-PA), is licensed for use in selected patients within 4.5 hours of stroke in Europe and within three hours in the USA. There is an upper age limit of 80 years in some countries, and a limitation to mainly non-severe stroke in others. Forty per cent more data are available since this review was last updated in 2009.

OBJECTIVES:

To determine whether, and in what circumstances, thrombolytic therapy might be an effective and safe treatment for acute ischaemicstroke.

SEARCH METHODS:

We searched the Cochrane Stroke Group Trials Register (last searched November 2013), MEDLINE (1966 to November 2013) and EMBASE (1980 to November 2013). We also handsearched conference proceedings and journals, searched reference lists and contacted pharmaceutical companies and trialists.

SELECTION CRITERIA:

Randomised trials of any thrombolytic agent compared with control in people with definite ischaemic stroke.

DATA COLLECTION AND ANALYSIS:

Two review authors applied the inclusion criteria, extracted data and assessed trial quality. We verified the extracted data with investigators of all major trials, obtaining additional unpublished data if available.

MAIN RESULTS:

We included 27 trials, involving 10,187 participants, testing urokinase, streptokinase, rt-PA, recombinant pro-urokinase or desmoteplase. Four trials used intra-arterial administration, while the rest used the intravenous route. Most data come from trials that started treatment up to six hours after stroke. About 44% of the trials (about 70% of the participants) were testing intravenous rt-PA. In earlier studies very few of the participants (0.5%) were aged over 80 years; in this update, 16% of participants are over 80 years of age due to the inclusion of IST-3 (53% of participants in this trial were aged over 80 years). Trials published more recently utilised computerised randomisation, so there are less likely to be baseline imbalances than in previous versions of the review. More than 50% of trials fulfilled criteria for high-grade concealment; there were few losses to follow-up for the main outcomes.Thrombolytic therapy, mostly administered up to six hours after ischaemic stroke, significantly reduced the proportion of participants who were dead or dependent (modified Rankin 3 to 6) at three to six months after stroke (odds ratio (OR) 0.85, 95% confidence interval (CI) 0.78 to 0.93). Thrombolytic therapy increased the risk of symptomatic intracranial haemorrhage (OR 3.75, 95% CI 3.11 to 4.51), early death (OR 1.69, 95% CI 1.44 to 1.98; 13 trials, 7458 participants) and death by three to six months after stroke (OR 1.18, 95% CI 1.06 to 1.30). Early death after thrombolysis was mostly attributable to intracranial haemorrhage. Treatment within three hours of stroke was more effective in reducing death or dependency (OR 0.66, 95% CI 0.56 to 0.79) without any increase in death (OR 0.99, 95% CI 0.82 to 1.21; 11 trials, 2187 participants). There was heterogeneity between the trials. Contemporaneous antithrombotic drugs increased the risk of death. Trials testing rt-PA showed a significant reduction in death or dependency with treatment up to six hours (OR 0.84, 95% CI 0.77 to 0.93, P = 0.0006; 8 trials, 6729 participants) with significant heterogeneity; treatment within three hours was more beneficial (OR 0.65, 95% CI 0.54 to 0.80, P < 0.0001; 6 trials, 1779 participants) without heterogeneity. Participants aged over 80 years benefited equally to those aged under 80 years, particularly if treated within three hours of stroke.

AUTHORS’ CONCLUSIONS:

Thrombolytic therapy given up to six hours after stroke reduces the proportion of dead or dependent people. Those treated within the first three hours derive substantially more benefit than with later treatment. This overall benefit was apparent despite an increase in symptomatic intracranial haemorrhage, deaths at seven to 10 days, and deaths at final follow-up (except for trials testing rt-PA, which had no effect on death at final follow-up). Further trials are needed to identify the latest time window, whether people with mild stroke benefit from thrombolysis, to find ways of reducing symptomatic intracranial haemorrhage and deaths, and to identify the environment in which thrombolysis may best be given in routine practice.”

Post-publication commentary:   Ryan Radecki2014 Aug 04 09:38 a.m.    “The tPA Cochrane Review Takes Us For Fools”   It’s been 5 years since the last Cochrane Review synthesizing the evidence regarding tPA in acute ischemic stroke. Clearly, given such a time span, in an area of active clinical controversy, a great deal of new, important, randomized evidence has been generated!                   Or, sadly, the only new evidence available to inform practice is IST-3 – a study failing to demonstrate benefit, despite its pro-tPA flaws and biases. So, it ought not be a very exciting update, considering the 2009 version included 26 trials, and the 2014 update now includes only 27 trials. Their summary conclusion, with only additional evidence of regression to the mean, ought remain essentially the same, or even less optimistic, right?

Interv Neurol. 2014 May;2(3):97-104. doi: 10.1159/000356087.

Future directions for intra-arterial therapy for acute ischaemic stroke: is there life after three negative randomized controlled studies?

Maingard J1, Yan B2.   Royal Melbourne Hospital, Melbourne, Vic., Australia.

The three randomised controlled trials, Interventional Management of Stroke III (IMS3), Mechanical Retrieval and Revascularization of Stroke Clots Using Embolectomy (MR RESCUE) and Synthesis Expanasion: A Randomized Controlled Trial on Intra-Arterial Versus Intravenous Thrombolysis in Acute Ischaemic Stroke (SYNTHESIS EXP) showed no significant difference in clinical outcomes comparing intra-arterial (IA) therapy with intravenous thrombolysis. This article will explore the reasons for failure to show superiority of IA therapy.:

There are many reasons for the disappointing results of the three randomised controlled trials. Opposing views on IA therapy exist. Critics argue that only a small percentage of patients will be eligible for IA therapy and that it will never be cost-effective. Additionally, current trials have failed to address superior recanalization rates of new generation devices and lack of patient selection by advanced imaging. Time-to-treatment is longer in these randomised controlled trials and stroke outcomes were worse than anticipated. The current randomised controlled trials also took long periods to complete. There is emerging evidence that general anesthetic negatively influences outcome. Next generation trials will attempt to address these issues. Key Messages: There are disparate explanations for the disappointing results from the three IA therapy randomized controlled studies. Poor recanalisation rates with first generation endovascular devices, lack of advanced neuroimaging to aid in patient selection, lack of data surrounding the use of general anaesthesia, and prolonged time-to-treatment are potential contributors to negative results. The new generation of trials has the potential of addressing these pressing issues.

DANGEROUS MEDICAL NEGLECT OF ESSENTIAL SUPPLEMEMENTS eg CoQ10.

Like appropriate HRT and marine EPA-DHA, the plant biological metformin and the human biological CoQ10 ubiquinone are antioxidants, nitric oxide promoters and insulin sensitizers ; and thus significantly lower the  incidence of diabetes, ischemic heart disease, hypertension, vertigo and heart failure as well as cancer; and thus premature aging, disability and death.

Like all our key biologicals, the fat-soluble CoQ10 reduces with aging below our necessary maintenance levels both by failing body production and by failing  diet; and thus becomes essential to supplement ie a vitamin; but especially with disease including diabetes, cancer etc; and in addition is reduced by frying; by the cholesterol-busting statins; by thiazides; by the original biguanide phenformin, as well as some sulphonylureas; by the anaesthetic halothane; by the tricyclic antidepressants; and by some betablockers eg propanolol, metoprolol and alprenolol.   So CoQ10 deficiency becomes universal from middle age, especially on some conventional drugs.

Studies of metformin show that- perhaps through reduced absorption of nutrients from the bowel- it lowers levels of vitamins folic acid and B12; but unlike with phenformin, there are no reports on Pubmed or Google of metformin lowering CoQ levels or vitamin B6 in any species.

Hence although they significantly lower vascular disease, metformin as well as fish oil and appropriate HRT have no benefit in lowering homocysteine level- which mainly vitamins B6 , B9 and B12 do..

But insulin resistance is at the core of the modern pandemic of fattening and hence all common major degenerative diseases of aging. Metformin, appropriate vitamins- minerals, HRT, fish oil and our other biologicals are the most pluripotential and life-extending ‘drugs’ we have; and the failure of some to lower homocysteine as a cardiovascular risk is more than easily compensated by adding  to metformin fish oil and HRT  a simple cocktail of B12, folic acid, coQ10 and other insulin sensitizer /antioxidants like vitamin D & K, calcium, magnesium, zinc, chromium , vanadium, and the major synergistic insulin-sensitizing biologicals like arginine, carnitine, ribose, n-acetyl cysteine, MSM, bioflavinoids, the herbs like garlic, ginger, curcumin, stevia, fenugreek etc; as well as plants which do not as yet show insulin-sensitizing property, but indirectly do so by lowering appetite eg coleus and gymnema.

So it is malpractice, dangerous neglect not to include all of these natural nutritional supplements against aging and all disease, including especially as backup for essential designer drugs (psychotropes, diuretics, statins, anaesthetics, prednisone, betablockers, chemotherapy, antibiotics)- none of which address the root causes of the major chronic degenerative diseases, often through aggravating eg insulin resistance, obesity and multiple deficiencies.

Common sense cannot be too strongly stressed: unlike supplements, virtually all invented ie designed modern drugs have major adverse effects at therapeutic or only slightly high doses. All established supplements discussed above eg metformin, vitamins, minerals are safe – and often curative- within reasonable dose range and balance adjusted gradually to tolerance.

A few like metformin and vitamin C may be poorly metabolized ie tolerated in a few people, hence should ALWAYS be started in very low dose and built up gradually to tolerance- usually a few grams a day. Many modern prescription designer (not natural) chronic drugs are potentially risky (but never curative) even well within the recommended prescribed dose.

So if designed ‘drugs’ are combined with supplements, it is the drugs – not supplements- which should be reduced to prevent eg bloodpressure, bloodsugar, cholesterol or bloodclotting from decreasing too far. Since most drugs are based on natural supplements, it is to be understood that appropriate supplements can often make prescription drugs and further tests unnecessary. Your medical scheme, medicines supplier and doctor may not like this, since it makes them feel redundant!

Fighting the 8th AGE: the mandatory panacea metformin and other natural supplements.

Exciting new anti-aging evidence has been published this year:

The Bard  spelled out the 7 ages of man. Now we know we have to deal with more AGEs – Advanced Glycation End Products- , and more evidence to prolong the healthy ages of man.

GLYCATION: some of us are fudge addicts. Fortunately with the natural supplements available, we can have  a little of our cake and safely eat it.

But as Wiki details,  such  lethal exogenous glycations and (AGEs) Advanced Glycation Endproducts “are typically formed when sugars are cooked with proteins or fats (eg fudge, baked puddings, sweet crackling/baked beans !). Temperatures over 120°C (~248°F) greatly accelerate the reactions, but so do  lower temperatures with longer cooking times. These compounds are digested with about 30% efficiency. Browning reactions (usually Maillard type reactions – like fudge, crackling!) are evidence of pre-formed glycations. Indeed, sugar is often added to products such as french fries and baked goods to enhance browning. Glycation may also contribute to the formation of acrylamide, a potential carcinogen, during cooking. Until recently, it was thought that exogenous glycations and AGEs were negligible contributors to inflammation and disease states, but recent work has shown that they are important.”

“Although most   research work has been done with reference to diabetes, these results are important for all, as exogenous AGEs are implicated in the initiation of retinal dysfunction, cardiovascular diseases, type II diabetes, cancer and many other age-related chronic diseases. Food manufacturers have added AGEs to foods, especially in the last 50 years, as flavor enhancers and colorants to improve appearance. Foods with significant browning, caramelization, or with directly added preformed AGEs can be exceptionally high in these proinflammatory and disease initiating compounds. A long list of foods with very high exogenous AGEs includes:  donuts, barbecued meats, cake, and dark colored soda pop”

This explanation of one of the root causes of the multisystem degenerative diseases of aging dispels the myths that the fast food chain and what the  Drug Industry promotes are healthy, that we need a patent drug per disease eg statin for lipidemia, antihypertensives for hypertension, anti thrombotics for thromboses,  anti-inflammatories  for pain, etc.

GALEGA METFORMIN: THE LONGEST-USED ANTIGLYCATION MEDICINAL:  The longest randomized controlled drug trial RCT ever, the UKPDS (Holman 2008) in type 2 diabetes DM2 showed that long term metformin double-blind for up to 20 years (mean 13.6yrs) (and up to 30years open use), lowers all-cause morbidity and mortality by about 1/3.  Other anti-diabetic drugs eg Sulphonylureas by contrast do little but lower hyperglycemia – without reducing mortality, but adding major risk of hypoglycemia – increasing the risk of dementia long term..

According to Schnider and Kohn from Ohio in 1980 (via Pubmed) , the concept of advanced  glycation/glycosylation in human aging and diabetes was  already well described, so the clinical concept is over 35 years old — but metformin has been under intensive research since 1922 ie for over 85years, and in human use (as the parent herb galega officinalis) for thousands of years – although the first mention on Pubmed of metformin as a blocker of glycation end products was in 1995. .

A new Dutch study (Kooy 2009) in humans has confirmed that metformin (850-2550mg/d) in the medium-term (a mean of 4.3yrs) added to insulin in DM2 lowers macrovascular endpoints by 39% p.02, weight by a mean of 3kg, and insulin requirement by 20iu/d.

A Buenos Aires study (Schurman 2009) notes that “AGEs  are implicated in the complications of diabetes and aging, affecting several tissues: in bone cells in culture, metformin treatment of osteoblastic cells prevented these AGE-induced alterations.”

There can be no doubt that,  given that the lethality of advanced obesity and  DM2 is as bad as smoking, it is crucial to reverse early ie prevent from developing all the mechanisms of obesity- diabetic damage including from hyperglycema itself; wasting from intracellular energy deficit due to insulin resistance; oxidation, nitric oxide deficiency; and above all else, AGEs from sugars fusing with fats or protein – especially fructose.  “It appears that fructose and galactose have approximately ten times the glycation activity of glucose, the primary body fuel. Glycation is the first step in evolution of these molecules through a complex series of very slow reactions in the body known as Amadori reactions, Schiff base reactions, and Maillard reactions; all lead to AGEs.  Some AGEs are benign, but others are more reactive than the sugars they are derived from, and are implicated in many age-related chronic diseases such as: type I and II diabetes mellitus (beta cell damage), cardiovascular diseases (endothelium, fibrinogen, and collagen are damaged), Alzheimer’s disease Vitek ea 1994 (amyloid proteins are side-products of the reactions progressing to AGEs), cancer (acrylamide and other side-products are released), peripheral neuropathy (myelin is attacked), and other sensory losses -deafness ( demyelination) and blindness (mostly  microvascular damage in the retina).”

“This range of diseases is the result of the very basic level at which glycations interfere with molecular and cellular functioning throughout the body. Glycated substances are eliminated from the body slowly, since the renal clearance factor is only about 30% ie half-life about double the average cell life. As a consequence, long-lived cells (such as nerves, brain cells), long-lasting proteins (such as eye crystalline and collagen), HBA1c and DNA may accumulate substantial damage over time. Metabolically-active cells such as the glomeruli in the kidneys, retina cells in the eyes, and beta cells (insulin-producing) in the pancreas are also at high risk of damage. The endothelial cells of the blood vessels are damaged directly by glycations, implicated in atherosclerosis. Atherosclerotic plaque tends to accumulate at areas of high blood flow (such as the entrance to the coronary arteries) due to  increased presentation of sugar molecules, glycations and AGEs at these points. Damage by glycation results in stiffening of the collagen in the blood vessel walls, leading to high blood pressure. Glycations also cause weakening of the collagen in the blood vessel walls, which may lead to micro- or macro-aneurysms; causing strokes if in the brain.”.

As Desai & Wu from University  Saskatchewan  sum up  2007,” AGEs are unavoidable byproducts of various metabolic pathways formed by reactive metabolic intermediates such as methylglyoxal (MG), glyoxal, and 3-deoxyglucosone. These reactive intermediates bind to proteins, DNA, and other molecules and disrupt their structures and functions, leading to aging – vascular complications of diabetes, atherosclerosis, hypertension, Alzheimer’s disease. In recent years, compounds that prevent the formation of AGEs or degrade the existing AGEs have been recognized or patented including 1. galega-metformin -guanidine; 2. pioglitazone (patented), 3 angiotensin blockers , 4) pentoxyfylline (patented), 5) metal ion chelators desferoxamine and penicillamine, 6) antioxidants such as vitamin C or E, etc.. ”

CROSS-LINKAGE AND AGING: Ward Dean 2009 spells out “the Crosslinkage Theory of Aging: AGEs and Crosslinkages – New Respect for Crosslinkage Theory.  Dr Johan Bjorksten in 1941 first proposed The Cross-linkage Theory of Aging   that aging was caused by inter- and intramolecular crosslinks in proteins, nucleic acids, and other vital macromolecules that caused them to gradually stiffen and lose their function”.

OTHER ANTI-AGEs BLOCKERS: Cataract formation is associated with low vitamin C (Tessier 1998); while Quian ea in 2000 showed that both vits C & E lowered AEGs in diabetic rats. Other natural AGEs blockers include taurine; L-Carnosine, L-Arginine, DMAE dimethylaminoethanol ;   PABA (para aminobenzoic acid); Thiamine HCl ; Alpha R Lipoic acid; Pyridoxal 5’ phosphate;  and to inhibit Amadori products: EDTA,  vits B1,B6, C & E , coQ10, Green Tea, Hawthorn, Grape Seed, Milk Thistle, Ginger Root, Ginkgo, bioflavinoids (Morimitsu 1995 ); curcumin ; and melatonin (Sailaja 2000);  to which one can add for antiaging:  huperzine A and DMAE.

Many companies are racing to market new ie patentable synthetic anti-AGEs agents like peptides ; benfotiamine and pyridoxamine . But as with some 1000 available natural insulin sensitizers, there are plenty of natural anti-AGEs supplements, starting with : galega officinalis (50% guanidine with negligible content of galegine) and it’s extracts aminoguanidine, galegine and dimethylguanidine-metformin. Already in 1999 Tanaka ea showed in rats that metformin treatment may be effective in the prevention of diabetic complications through not only lowering plasma glucose, but also directly inhibiting AGEs formation.   Sowers 2002 theorizes that the reason that statins “do not reverse endothelium-dependent and -independent vascular dysfunction in DM2 (in contrast to in non-diabetics) is precisely because of AGEs.  But Jinnouchi 2006 shows that atorvastatin also reduces AGES.

These studies affirm that  METFORMIN is the Gold Standard (Bailey ea 2007: Merck Sante), arguably both the safest and the most pluripotential therapeutic agent ever discovered, being an age-old medicinal plant extract (Werner and Bell 1922).

So we do not need patent designer inhibitors (of AEGs  or reactive oxygen species or insulin resistance or lipidemia or inflammation or appetite-weight gain) – there are dozens available from nature, with galega- metformin the longest and  broadest potential proven and used, that when simply and safely titrated slowly upwards to good tolerance, at least halves the incidence of new diabetes and thus adds at least a decade to health and longevity.

THE GODDESS PANACEA: A panacea is defined as a “cure all”, to “retard the aging process”, and to increase the “quality of life”. Today a balanced diet and lifestyle is far from a guarantee of healthspan.  Despite  denial by  the food and drug industry (aka the FDA, the Disease Industry  who want to suppress the old so as to sell  their   new  designer patents) metformin fulfills all the criteria for a panacea in a stressed fattening population, from promoting copulation, conception and pregnancy to healthy  old age.

An old study from Germany (Hammes 1996)  shows again a potential trap of testing one substance in isolation and in rodents – in this case, EPA + DHA (as Maxepa) about 130mg/day for 6 months if anything harmed the retina in diabetic rats. Does this have any bearing on the global benefits of natural EPA+DHA and brod supplements  in  humans?

By contrast, El-seweidy ea in Egypt in 2002  showed also in diabetic rats that “combined treatment with galega (aminoguanidine) and omega3  markedly reduced all the adverse blood markers and nearly restored the atrophy of islets of Langerhans and the peripheral lymphocytic infiltration compared to untreated diabetic rats and those treated only with guanidine.”

The cardinal principle of nutrition and medicine is synergy- that we do not or should not eat single foods in isolation, nor expect disease to respond to a single extract/medicine;   nutrients and nutriceuticals complement each other. This is obviously contrary to the imperative of the Disease Industry to sell a profiteering rainmaker snake-oil per disease..

GALEGA/METFORMIN AS MANDATORY PREVENTION AND THERAPY: The common lethal poisons that humans consume – sugar, salt, alcohol, aspirin, paracetamol, ibrufen and cigarettes – are freely sold over the counter.

Metformin must thus similarly be released for over the counter sale as the only proven panacea (aside perhaps from fish oil) and the only drug ever in RCT for 20year AND  proven to be without any major adverse effect – including for halving deaths in diabetes, and (in four major trials on four different continents) halving the incidence of new diabetes in the overweight, and reversing progressive weight gain. And it can be simply and cheaply manufactured from basic chemicals in 5 minutes.

It  must thus be made mandatory prescription to tolerance for prevention obesity and diabetes in the overweight (ie those whose BMI persists despite attempted correction above about 25kg/sqm),  let alone in all diabetics.

THE LIE OF MODERN CHRONIC DRUGS: HIGHLY EFFECTIVE COMPLEMENTARY ARTHRITIS TREATMENTS

Further to the BBC’s  and The  Yorkshire Post‘s scorning complementary arthritis treatments this week:

the Aberdeen study that they were reporting is now published in an 😯 page report on line .

In fact the condemnation the media heap on complementary products is nonsense, rank hypocrisy on the principle that only bad news pays.

No single modern chronic drug addresses the cause ie the cure of the chronic major degenerative diseases. Hyperglycemia is not the cause of diabetes to justify sulphonylureas or insulin; ,  cholesterol the cause of atheroma to justify statins;   hypertension the cause of Essential Hypertension to justify the plethora of antihypertensives, or pain/swelling the cause of arthritis to justify the toxic NSAIDs.

The Aberdeen ARC Arthritis Research Campaign report showed

5/5 ie major benefit of fish oil in rheumatoid arthritis RA (let alone it’s all-system benefits) ;

5/5 ie major  benefit of topical capsicain gel for osteoarthritis OA ;

4/5 for SAMe in OA;

3/5 benefit in osteoarthritis of many individual herbs separately;

3/5 benefit each of chondroitin and glucosamine for osteoarthritis- but they neglected to note the combination taken for at least 3 months actually slowly restores lost  cartilage loss and thus reverses pain and disability, restoring good function in mild to moderate  disease  = 5/5. In fact the recently published USA 9-site GAIT trial (Sawitzke ea) showed that the combination actually reversed cartilage loss in mild to moderate OA.

The ARC report  also, strangely, omits the overriding principle of all major diseases- that since these eg hypertension, OA,  RA, vascular disease, type 2 diabetes, depression- are multifactorial in origin, in more than the mildest cases(as in cancer, and serious infections eg AIDS, tuberculosis, septicemia, helicobacter)  therapy is always better with combination synergistic agents in lower dose rather than one agent  in high dose; and that  treatment must include hitting the causative factors to try to achieve cure, not just palliation.

Hence they fail to mention the obvious,  that

Arthritis  is always best treated with anti-inflammatories  – including fish oil and other NSAIDs,  apart from

*for RA- at least three remittive allopathics eg prednisone and methotrexate,  plus gold, chloroquine or salazopyrin;

and

*for  mild to moderate  OA-  the  curative ie remittive  combination of chondroglucosamine CG  in addition to temporary pain-relievers; since OA is inevitably a future complication of all chronic arthritis, their treatment should also include CG;

and that there is no evidence that combination of allopathic ie patented  designer NSAIDs and analgesics are any better let alone as safe for pain and stiffness relief of  the two common major arthritic conditions as combination of safe complementaries eg chondroglucosamine,  fish oil, boswellia, bromelain,  cat’s claw, curcumin, nettle , SAMe, phytodolor and vitamins eg pantothenic acid, nicotinamide, ascorbic acid, pyridoxine,D, E  and vit K ; without including eg white willow and devil’s claw which can  evoke aspirin-like allergy.

KILLING PAIN AND FEVER, NOT THE PATIENT

 The BBC trumpets Edinburgh scientists’ attempts to find an antidote for paracetamol/ acetaminophen overdose.

 

But why  is  marketing  of such synthetics allowed, when they are both weak and potentially fatal at  a dose of as little as 4 to 6 tablets? And when they are no better than safe natural equivalent analgesics?

 

The Politicians and Regulators who allow the marketing of paracetamol should be prosecuted for gross negligent homicide – according to the BBC report, they are responsible annually for some 200 deaths and 20 liver transplants  due to paracetamol.

The regulatory tolerance of paracetamol absolves manufacturers and distributors of  culpability-  but does  not morally justify sale of such poison by any trader.

Why allow sale of an unnecesary analgesic that permits such painless slow suicide?

So why do we need more antidotes when there is no reason to market paracetamol?

Just as why do we need an antidote to the gross toxins sugar and tobacco smoking  and liquor when there is no need to market and (ab)use them?

 And where is the need for a better antidote to paracetamol than the long-proven natural N-acetyl cysteine  and activated charcoal. More practical would be to simply include a little Nacetyl cysteine, lipoic acid  and eg milk thistle in paracetamol.  We easily include some calcium carbonate and B12 in metformin  to minimise it’s negligible adverse effects; but then metformin is the cheapest most multisystem- beneficial and longest proven medicine- a veritable panacea- ever discovered; whereas paracetamol is anything but.

 

Remember that pain, fever, fatigue are symptoms, not a disease.

Synthetic painkillers and anti-inflammatories can and do  all kill –

      – but they never cure..

 

So for common pain, we should recognise and treat the disease , not mask the pain/fever

Eg toothache  – dental care;

     Other Face pain- sinus-mucolytics; neuralgia eg shingles;

     Headache- tension ; migraine; check bloodpressure; eyes; posture; physical therapy*.

     Backache- posture; weightloss; chondroglucosamine; physical therapy*

     Muscle/joint pain- weightloss; seek cause of referred pain;  physical therapy*;

                       In older people- tesosterone-estrogen deficiency.

     Depression – counselling; natural antidepressants eg 5HTP; StJohn’s wort.

     Heartburn, irritable bowel- diet; antacids; glutamine.

     Osteoporosis- supplements (minerals, vits, HRT);  exercise.

     Fever- pinpoint the cause; boost immunity.

     Dehydration- drink 2 litres fluid a day, without sugar, aspartame or caffeine!

     Lateral chest pain – most commonly simple root pain from the back;

     Shingles- boost immunity; topicals; perhaps brief course of cortisone.

     Pelvic pain  (other than menstrual) – infection/ cancer- see a doctor;

    Colic, central chest/ abdominal  pain –  see a doctor.

 

PHYSICAL THERAPY* includes:

     Massage with or without natural anti-inflammatory ointment;

     Stretching;  manipulation; Acupuncture, pressure points;

     Progressive exercise and posture improvement.

 

ORAL “PAIN KILLERS” include:

A natural mix of: MSM, catsclaw; curcumin; bromelain; boswelia;

             vits B 3,5,6,C,D  plus  calmag;          plus fish oil 2 – 4gm/d.

    This safe combination has none of the serious (potentially fatal)  risks of

  -synthetic painkillers eg paracetamol, aspirin, codeine, brufen- voltaren(NSAIDs);

  -risky (allergenic) natural analgesics eg willow, devil’s claw.

  -alcohol combined with synthetic drugs.

 

And all trials show that synthetics

     eg aspirin, paracetamol, NSAIDs, antidepressants

       have no advantage or benefits over the natural ones – just more risks.

           

  For localised pain eg  AROUND A JOINT ,  a targetted injection of

    Cortisone with local anaesthetic is often the best solution of both pain and cause.

 

Progressive pain requires medical investigation of the cause.

 

FOR OPTIMAL AGING IN MEN AND WOMEN: APPROPRIATE NATURAL SUPPLEMENTS INCLUDE HUMAN HRT:

 ie  

melatonin –  essential unless you get plenty of sleep and sunlight;

 

insulin sensitizers including Vitamin D,  fish oil  if the slightest overfat,

even before diabetes develops;     

          plus  balanced

*thyroid+cortisone+estrogen +progesterone+teststerone

if their measured levels are not optimal. *these  require medical supervision.

 

 

Remember that the aging ie postmenopausal woman

who still cares about her  looks

should use estrogen-progesterone  cream on the face,  but

for best (ie cheapest) absorption- and optimal mood, bone and pelvic floor protection

use the testosterone  cream  internally.

(or for lowest cost- use   progesterone cream  on  the face.

plus  testosterone + estradiol by tiny injection ~ fortnightly),

.

In both genders,

like balanced estrogen plus  testosterone,

solo progesterone  protects the

skin, hair, heart, breasts, mood, brain, thyroid,  bladder, immunity  and circulation,

but not   strength, bones or hearing

 

only the  right  balance of estrogen  and testosterone  does so.

 

Remember- there is no upper age limit on appropriate supplements

the key to health is –  we don’t stop eating because we age!

We  may need less food, but we need more natural micronutrient supplements including human hormones to make up for their  increasing (relative) deficiency  in our food chain and our own  metabolic reserves, as well as to  counter  increasing pollution and the demands of increasing  longevity.. 

See the HRT  and supplement papers  below, and the recommended condition-specific supplement product information.. For specialist  internist consultation on appropriate supplements including HRT for individual circumstances, email your concise health details to info@healthspanlife.com ..