Creation vs Evolution : The Genesis of Time Matter and Life

 

Creation vs Evolution

The Genesis of Time Matter and Life

https://sg.docworkspace.com/l/sIEnzzKWFAcuMj6YG

 

Mysteries on the Orgin of Life on Earth

 Theories on the Origin of Life

Conceivably the most central but the least understood biological mystery is how did life originate on this planet?  It is the fundamental mystery to many scientific and philosophical thinking as well as trying to ask if we are alone in this entire universe and assuming there is no other extraterrestrial life elsewhere. Can we assume these five events may have taken place when life first originated:

1. The origin of life is an outcome of a supernatural event, namely one that is beyond the powers of all physical, chemical and biological sciences as we know them.
2. The origin of life is an abiogenesis event meaning life arose from non -living chemicals on Earth more than 3.5 billion years ago. Abiogenesis proposes that the first life-forms generated were very simple and through a gradual process became increasingly complex through the process of evolution and adaptation.
3. Life is eternal. It has no beginning or an end.  It arrived on Earth at the time of Earth’s origin and began to flourish thereafter due to our ambient and conductive environment that host them.
4. Life arose on the early primordial oceans by a series of random aggregation of nucleic acids brought about by nitrogen-fixing, oxygen, hydrogen, phosphorous coming together through continuous discharge of lightning, ultraviolet light into the first DNA / RNA molecules.
5. It was implanted into this Earth by extraterrestrial dust from passing comets from the Oort Cloud. 

Panspermia theory on life brought to earth by a passing comet from the Oort Cloud:

https://scientificlogic.blogspot.com/search?q=panspermia

6. Based on our traditional, religious and philosophical beliefs, for example how heavens, earth and life were created as given in Genesis.  

By the time of the Renaissance, there was scientific thinking on the origin of life. There were thoughts   that spontaneous generation of animals from putrefying matter was impossible. 

During the mid-17th century, the British physiologist William Harvey discovered that every animal comes from an egg. The Italian biologist, Francesco Redi, showed in the latter part of the 17th century that the maggots in meat came from flies’ eggs, deposited on the meat.

In the 18th century an Italian priest, Lazzaro Spallanzani, presented that life can only come from the fertilization of eggs by sperm for the reproduction of mammals. But the idea of spontaneous generation was still there. Even though it was clear that large animals developed from fertile eggs, it was still  believed that smaller life-like microorganisms, spontaneously generated from debris. Many felt it was obvious that the omnipresent microscopic creatures generated continually from inorganic matter.

Maggots were prevented from developing on meat by covering it with a fly proof screen. But it was argued that fruit juice could not be kept from fermenting by putting any netting whatsoever over it. There goes that the origin of life is spontaneous that dies hard. 

Spontaneous generation was the subject of a great debate between the French bacteriologists Louis Pasteur and Félix-Archimède Pouchet in the 1850s. Pasteur successfully presented evidence that even the most minute creatures came from “germs” that floated downward in the air, but that they could be blocked from access to foodstuffs by suitable filtration. Pouchet argued, forgivably, that life must somehow arise from non-living matter; if not, how had life come about in the first place?

Pasteur’s experiments showed defensively that life does not spontaneously appear from non-living matter. But the American historian James Strick reviewed the controversies of the late 19th century between evolutionists who supported the idea of “life from non-life” and their responses to Pasteur’s religious view that only God can make life. So, the controversies went on, and even till today we are not too sure. 

When I was doing a postdoctoral course on evolution at the University of Cambridge in 2018, I brought forward an observation in a technical forum paper discussion on fish that mysteriously appeared in holes and ponds artificially dug up in isolated areas.  After many months when rainwater filled up the holes and ponds, fish were found there far away from any river or sea. There were many discussions among the academics at Cambridge with many similar observations and studies done elsewhere and quotes showing the same, but with no satisfactory explanation or conclusion given.

The microbiological conviction that life must always come from preexisting life in the form of cells subdued many post-Pasteur scientists from discussions of the origin of life at all. Many were, and still are, reluctant to offend religious sentiment by researching this provocative subject.

But the valid issues of life’s origin and its relation to religious and scientific thinking raised by Strick and other authors, such as the Australian Reg Morrison, persist today and I think this debate will never end even among the scientists, let alone religious thoughts and beliefs.

Toward the end of the 19th century, Swedish chemist Svante A. Arrhenius proposed that life on Earth arose from “panspermia,” microscopic spores that wafted through space from planet to planet or solar system to solar system by radiation pressure. So did Fred Hoyle (1915–2001) and Chandra Wickramasinghe (born 1939) were powerful proponents of panspermia theory.

In 1974 they proposed the hypothesis that some dust in interstellar space was largely organic or carbon-based, which Wickramasinghe later proved to be correct. Hoyle and Wickramasinghe further contended that life forms continue to enter the Earth's atmosphere, and may be responsible for epidemic outbreaks, new diseases, and the genetic novelty necessary for macroevolution.

  

This idea, of course, avoids rather than solves the problem of the origin of life. It seems extremely unlikely that any live organism could be transported to Earth over interplanetary or even through vast interstellar distances without being killed by the combined effects of cold, desiccation in a vacuum, and radiation.

However English naturalist Charles Darwin did not commit himself to the origin of life. Darwin wrote about “On the Origin of Species” through Natural Selection. He showed the diversity of organisms and their characteristics that can be explained as the result of natural processes. Darwin published his monumental books On the Origin of Species in 1859 and The Descent of Man in 1871.

Then came the famous British biologist T.H. Huxley in his book Protoplasm: The Physical Basis of Life (1869) and the British physicist John Tyndall in his “Belfast Address” of 1874. Both these scientists defended that life could be generated from inorganic chemicals. But they had extremely vague ideas about how this might be accomplished. The words “organic molecule” means a class of chemicals uniquely of biological origin.

 Despite the fact that urea and other organic (carbon-hydrogen) molecules had been routinely produced from inorganic chemicals since 1828, the term organic meant “from life” to many scientists.

Hence, the word organic does not mean it has to be of biological origin. The origin-of-life problem largely reduces to the determination of an organic, nonbiological source of certain processes such as the identity maintained by metabolism, growth, and reproduction as in autopoiesis.

Darwin’s thinking was: “It is mere rubbish thinking at present of the origin of life; one might as well think of the origin of matter.” The two problems are in fact curiously connected. Indeed, modern astrophysicists do think about the origin of matter. 

The evidence is undoubted that thermonuclear reactions, either in stellar interiors or in supernova explosions, generate all the chemical elements of the periodic table more massive than hydrogen and helium. Supernova explosions and stellar winds then distribute the elements into the interstellar medium, from which subsequent generations of stars. 

In fact, astronomers claim we are made from star dusts generated by a supernova explosion where elements landed as the soil of this earth from which God created man as a living soul by His breath. I believe this is where scientists and religion agree with each other on our origin.

 In the 1920s British geneticist J.B.S. Haldane and Russian biochemist Aleksandr Oparin acknowledged that the nonbiological creation of organic molecules in the present oxygen-rich atmosphere of Earth is highly unlikely but that, if Earth once had more hydrogen-rich conditions, the abiogenic production of organic molecules would have been much more likely.

The thinking is, if large quantities of organic matter were somehow synthesized on the primitive Earth, they would not necessarily have left much of a trace today. Our present atmosphere with 21 percent of oxygen produced by cyanobacteria, algal, and plant photosynthesis, and organic molecules would tend, over geological time, to be broken down and oxidized to carbon dioxide, nitrogen, and water.

As Darwin believed, the earliest organisms would have tended to consume any organic matter spontaneously produced prior to the origin of life.

The first experimental simulation of early Earth conditions was carried out in 1953 by a graduate student, Stanley L. Miller, under the guidance of his professor at the University of Chicago, chemist Harold C. Urey.

They made a mixture of methane, ammonia, water vapour, and hydrogen which were continuously sparked by electricity mounted higher in the apparatus. The discharge was thought to represent lightning in the primordial atmosphere.

 After several days of exposure to sparking, the solution changed colour. Several amino and hydroxy acids, familiar chemicals in contemporary Earth life, were produced by this simple procedure. The experiment is simple enough to show the presence of amino acids Ultraviolet light or heat was substituted as an energy source in subsequent experiments.

On the primitive Earth much more energy was available in ultraviolet light than from lightning discharges. At long ultraviolet wavelengths, methane, ammonia, water, and hydrogen are all transparent, and much of the solar ultraviolet energy lies in this region of the spectrum. The gas hydrogen sulphide was suggested to be a likely compound relevant to ultraviolet absorption in Earth’s early atmosphere.

 

Amino acids were produced by long-wavelength ultraviolet irradiation of a mixture of methane, ammonia, water, and hydrogen sulphide. At least some of these amino acid synthesis involved hydrogen cyanide and aldehydes such as formaldehyde as gaseous intermediates formed from the initial gases. The biologically abundant amino acids made readily under simulated early Earth conditions is quite remarkable. If oxygen is permitted in these kinds of experiments, no amino acids are formed. This has led to a belief that hydrogen-rich or oxygen-poor conditions were necessary for natural organic syntheses prior to the appearance of life.

But neither the presence of amino-acid or even the presence of DNA / RNA means the music of life itself. It must be something else that resides in these amino acids or neucleic acids and nucletides that make them alive. See my further arguments here: 

https://scientificlogic.blogspot.com/search?q=the+mystery+of+life

Under alkaline conditions, and in the presence of inorganic catalysts, formaldehyde spontaneously reacts to form a variety of sugars. The five-carbon sugars fundamental to the formation of nucleic acids, as well as six-carbon sugars such as glucose and fructose, are easily produced. These are common metabolites and structural building blocks in life today.

Additionally, the nucleotide bases and even the biological pigments called porphyrins have been produced in the laboratory under simulated early Earth conditions. Both the details of the experimental synthetic pathways and the question of stability of the small organic molecules produced are vigorously debated.

Nevertheless, most, if not all, of the essential building blocks of proteins (amino acids), carbohydrates (sugars), and nucleic acids (nucleotide bases which are the monomers can be readily produced under conditions thought to have prevailed on Earth in the Archean Eon. 

The search for the first steps in the origin of life has been transformed from a religious/philosophical exercise to an experimental science.

Polymers:

The formation of polymers, long-chain molecules made of repeating units of monomers, is a far more difficult experimental problem than the formation of monomers. Polymerization reactions tend to be dehydrations.

 A molecule of water is lost in the formation of a peptide from two amino acids or of a disaccharide sugar from two monomers. Dehydrating agents are used to initiate polymerization.

The polymerization of amino acids to form long protein-like molecules (“proteinoids”) was accomplished through dry heating by American biochemist Sidney Fox and his colleagues. The poly amino acids that Sidney Fox formed were not random molecules unrelated to life. Long polymers of amino acids were also produced from hydrogen cyanide and anhydrous liquid ammonia by American chemist Clifford Matthews in simulations of the early upper atmosphere.

Some evidence exists that ultraviolet irradiation induces combinations of nucleotide bases and sugars in the presence of phosphates or cyanides. Some condensing agents such as cyanamide are capable of being made under simulated primitive conditions. 

Despite the breakdown by water of molecular intermediates, condensing agents may quite effectively induce polymerization, and polymers of amino acids, sugars, and nucleotides have all been made this way.

That adsorption of relevant small carbon compounds on clays or other minerals may have concentrated these intermediates was suggested by the British scientist John Desmond Bernal which may have biological significance. Phosphorus, which with deoxyribose sugar forms the mainstay of DNA is integrally involved in cell energy transformation and membrane formation, is preferentially incorporated into organic molecules.

The early ocean and lakes may have been a dilute solution of organic molecules. If all the surface carbon on Earth were present as organic molecules, or if many known ultraviolet synthetic reactions that produce organic molecules were permitted to continue for a billion years with their products dissolved in the oceans, a 1 percent solution of organic molecules would result. 

Haldane suggested that the origin of life occurred in a “hot dilute soup.” Concentration through either evaporation or freezing of pools, adsorption on clay interfaces, or the generation of colloidal enclosures called coacervates may have served to bring the organic molecules in question in contact with each other.

The essential building blocks for life were possibly produced in comparatively abundant concentrations, given conditions on the early Earth. Although pertinent, this is more akin to the origin of food than to the origin of life. If life is defined as a self-maintaining, self-producing, and mutable molecular system that derives energy and supplies from the environment, then food is certainly required for life.

Polynucleotides which are polymers of RNA and DNA can be produced in laboratory experiments from nucleotide phosphates in the presence of enzymes of biological origin using polymerases, and a preexisting “primer” nucleic acid molecule. If the primer is absent, polynucleotides are still formed, but they lack specific genetic information. 

Once such a polynucleotide forms, it can act as a primer for subsequent syntheses.

Even if such a molecular population could replicate polynucleotides, it would not be considered alive. The polynucleotides tend to hydrolyse in water.

In the early 1980s American biochemist Thomas Cech and Canadian American molecular biologist Sidney Altman discovered that certain RNA molecules have catalytic properties. They catalyse their own splicing, which proposes an early role for RNA in life or even in life’s origins. Only the cooperation of the two kinds of molecules (proteins and nucleic acids) segregated from the rest of the world by an oily membrane makes the growth process of life on Earth possible. The molecular machinery ancillary to the operation of the genetic code, the instructions that determine the linear order of amino acids in proteins from nucleotide base pairs in nucleic acids, namely, the activating enzymes, transfer RNAs, messenger RNAs, ribosomes, etc, may be the product of a long evolutionary history among natural, thermodynamically favoured, gradient-reducing complex systems.

These rules are produced according to instructions contained within the code. The American biophysicist Harold J. Morowitz argued persuasively that the origin of the genetic system, the code with its intricate molecular apparatus, occurred inside cells only after the origin of life as a cyclic metabolic system. 

Similarly, the American theoretical biologist Jeffrey Wicken pointed out that replicating molecules, if they appeared first, would have had no impetus to develop a complex cellular package or associated protein machinery and that life thus probably arose as a metabolic system that was stabilized by the genetic code, which allowed life’s second law-favoured process to continue ad infinitum.

The earliest living systems:

Most organic molecules made by living systems inside cells show the same optical activity, that is, when exposed to a beam of plane-polarized light, they rotate the plane of the beam. Amino acids rotate light to the left, whereas sugars, called dextrorotatory, rotate it to the right.

Organic molecules produced artificially lack optical activity because both “left-handed” and “right-handed” molecules are present in equal quantity. Molecules of the same optical activity can be bring together in complementary ways like the stacking of right-handed gloves. The same monomers can be used to produce longer chain molecules that are three-dimensional mirror images of each other; mixtures of monomers of different handedness cannot.

 

Cumulative symmetry is accountable for optical activity. At the time of the origin of life, organic molecules, corresponding both to left- and right-handed forms, were no doubt formed as they are in laboratory simulation experiments today: both types were produced. But the first living systems must have engaged one type of component, for the same reason that carpenters cannot use random mixtures of screws with left- and right-handed threads to produce a tool.

 

Whether left- or right-handed activity was adopted was probably a matter of random chance, but, once a particular asymmetry was established, it maintained itself.

Optical activity accordingly is likely to be a feature of life on Earth or on any planet. The probabilities may be equal of finding a given organic molecule or its mirror image in extraterrestrial life-forms if, as Morowitz suspects, the incorporation of nitrogen into the first living system involved glutamine, the simplest of the required amino acid precursors with optical activity.

The first living cells probably resided in a molecular Garden of Eden, where the pre-biological origin of food had guaranteed monomers that were available. The cells, the first single-celled organisms, would have increased speedily. But such an increase was eventually limited by the supply of molecular building blocks. Those organisms with an ability to synthesize scarce monomers, say A, from more abundant ones, say B, would have persisted.

The secondary source of supply, B, would in time also become exhausted. Those organisms that could produce B from a third monomer, C, would have preferentially persisted. The American biochemist Norman H. Horowitz has proposed that the multienzyme catalysed reaction chains of contemporary cells originally evolved in this way.

Multiple theories on life’s origin go on, each scientist proposes his own thoughts, others believe its origin is entirely the prerogative of an Intelligent Design whom we call God, the Maker of all things.

For further reading may I suggest an excellent book called “Origin of Life” by Jim Brooks, B. Tech. M Phil, PhD, C. Chem. FRCS, F. Inst Pet, FGS, Assoc BIT who is a geochemist and an oil explorationist with Britoil. He wrote a very interesting book describing the first moment of the Universe to the beginning of life on Earth in 158 pages. His ideas are an extension of mine.

Another article worth reading was written by the late prolific science writer Dr Isaac Asimov in his book “The Planet That Wasn’t” in his chapter “Silent Victory” how life on Earth began.

We could go on, and on discussing this mystery, but it is already very late into the night into the early hours before dawn, and I need to stop here.

Videos on Astronomy and on Covid Spread

 

Just for a change. Instead of writing articles on my own, here are some videos I recommend to readers on astronomy, and one on the Covid global spread.  

Universe Size Comparison | Cosmic Eye (Original HD)

https://www.youtube.com/watch?v=8Are9dDbW24

What would we see at the speed of light?

https://www.youtube.com/watch?v=vFNgd3pitAI

Life and Death: A Cosmic Perspective from Neil deGrasse Tyson

https://www.youtube.com/watch?v=EwncyLyTXQ4

Journey to the Edge of the Universe

1.   A Journey to the End of the Universe - YouTube

In the above video No 1, I fully agree with the narrator that we can never reach the speed of light in our journey to the end of the universe no matter how fast we accelerate our spaceship. We shall also never reach the edge of the universe no matter how much we try. I fully endorse this theory only if we are talking about ourselves who are physical and material, having a mass. 

It would require an infinite amount of energy for anything that has a mass to travel at the speed of light. 

The special theory of relativity of Einstein suggests that only particles with zero rest mass such as photons of light may travel at the speed of light, and that nothing may travel faster.

However, the soul leaving our physical body on death has no mass, and hence it can travel at the speed of light or even faster. See my explanation here:

Does A Human Soul Travel Faster than the Speed of Light?

2.   https://scientificlogic.blogspot.com/search?q=does+soul+have+mass•

3.   Journey to the End of the Universe

https://www.youtube.com/watch?v=QhM5zAVvOI4

4.   An Epic Journey from Earth to the Edge of the Universe

https://www.youtube.com/watch?v=H14TSlXuzcQ

Covid Pandemic:

https://www.youtube.com/watch?v=QGF-UNk3UdE

Dealing with Type 1 Diabetes Mellitus

 

 In the last article “The Assessment, Criteria for High Blood Pressure: Its Conventional vs Non-Drug Approaches” here:

https://scientificlogic.blogspot.com/2023/

posted on Thursday, July 20, 2023, we mentioned two most common chronic lifestyle diseases, namely hypertension and diabetes. 

We have already briefly discussed high blood pressure, their outcome and management using conventional drug-based approaches as well as very briefly listed in point forms, a range of other alternative therapeutic approaches to deal with this problem.

We shall now briefly discuss diabetes mellitus, the next most common disorder in all countries, especially among affluent societies.

First of all, diabetes mellitus is entirely different from another diabetes called "diabetes insipidus" that is a rare endocrine disorder involving the posterior pituitary peptide hormone, the antidiuretic hormone (ADH). This causes the fluids in the body to become out of balance, causing large amounts of urine output resulting in extreme thirst.

Diabetes insipidus also is called arginine vasopressin deficiency and arginine vasopressin resistance. We shall not deal with this here as it is different from diabetes mellitus commonly called just diabetes. 

We shall also not deal with type 1 diabetes here that requires insulin injections. Briefly, Type 1 diabetes, also called insulin-dependent diabetes (IDDM) or juvenile diabetes, normally develops in children, teens, and young adults, but it can happen at any age especially after type 2 diabetes has lost all its ability to produce insulin. 

Type 1 diabetes is less common than type 2—about 5 - 10% of people with diabetes have type 1.

In diabetes type 1, the pancreas does not make insulin, due to an auto-immune response that attacks the islet cells in the pancreas that make insulin. 

This may be due to viruses, genes, dietary factors or chemical exposure that trigger autoimmune response. Type 1 diabetes may also arise from chronic pancreatitis, or the result of pancreatic surgery. 

As type 1 insulin-dependent diabetes is comparatively rarer, we shall not discuss this further.   

In diabetes type 2, the pancreas makes less insulin than used to, and your body becomes resistant to insulin. This means your body has insulin, but stops being able to use it.

Diabetes mellitus is a world-wide epidemic that shall become wider and afflicting most people especially among the Indians and Malays in Malaysia. 

It was found that individuals with type 2 diabetes mellitus (DM) globally were over 30 million in 1983, 171 million in 2000, 220 million in 2009 and 330 million in 2018, 380 million in 2021. 

The prevalence rate seems to double every few years. From 1998 to 2009 the prevalence rate rose to a frightening rate 239 % in Canada alone and has been projected to rise sharply within the next 10 years and shall continue to rise. The Centre for Disease Control (CDC) in the United States projected a 40 % increase of DM among Americans over their lifetime. 

The same scenario we can expect in this country due to our changing fare (dietary lifestyle).

Type 2 DM is the most common ailment that afflicts the developed and developing world. The rising trend is attributable to other factors too such as obesity, sedentary lifestyles, aging population and improved survival rates among diabetics.

Type 2 DM is also linked to high healthcare costs. Figures taken from other countries, for instance in a report “An Economic Tsunami: The Cost of Diabetes in Canada” from 2009 the estimated cost of type 2 DM in 2010 was US $ 12.2 billion and projected to surge to US $ 16.9 billion by 2010, perhaps to US $ 30 billion by the end of this year 2023. We may have similar trends in Malaysia although data is scant and not well-studied.

       

Our hope is that type 2 DM is highly preventable, especially to reduce the risk of other linked diseases such as cardiovascular mortality by at least 10 percent or more.

Pathophysiology:

 The pathophysiology of type 2 DM is multifaceted and complicated, essentially consisting of hyperglycemia and impaired insulin secretion.

 Carbohydrate consumption and its breakdown into glucose for absorption triggers the release of insulin by the beta cells from the pancreas. Insulin in turn triggers the uptake of glucose by the cells through the GLUT-4 glucose transporter. 

Insulin resistance (IR) may ensue after exposure to chronically high serum glucose levels. Patients on steroid therapy and physical inactivity may also face high risk of developing type 2 DM. 

Scientists are in the opinion that type 2 DM is amplified by the peripheral cells inability to efficiently uptake glucose in response to insulin, or insulin becomes ineffective due to the absence of a coenzyme called glucose tolerance factor (GFT) that requires chromium and niacin to assist when the beta islet cells dysfunction. 

Insulin role in exciting cellular glucose uptake decreasing hepatic gluconeogenesis, together with increasing adipose tissue triglyceride synthesis, together with glycogen regulation and vascular quality are crucial factors in impaired 2 DM. 

Diabetes is ironically labelled as “starving amidst the feast” whereas, insulin resistance (IR) indicates impaired glucose transport into muscle cells that explains for the “starving” amidst the hyperglycemia “feast”  

Furthermore, cellular starvation feedback mechanisms exacerbate hyperglycemia by exciting hepatic gluconeogenesis and fat breakdown.

IR also stimulates the production of free fatty acids and inflammatory cytokines.

Inflammatory markers shown to be elevated in DM comprise C-reactive proteins, II -6, plasminogen activator inhibitor -1 (PAI -1), and tumor necrosis factor (TNF)- alpha, in addition to white cell count.

Adiponectin is an anti-inflammatory cytokine that has been demonstrated to reduce plasma levels of free fatty acids. High adiponectin is associated with improved lipid profiles, glycemic control, and reduced inflammation.  DM has also been shown to be associated with a reduction in adiponectin.

Most of the studies on type 2 DM pathophysiology were earlier concentrated on IR. However, the role of the pancreas has increasingly been recognized.  Beta islet cells are well accepted to produce insulin. However, these are not the only pancreatic islet cells. Alpha islet cells produce glucagon, considered an equivalent of insulin. The interaction between insulin and glucagon is typically very tightly synchronized.

 The increased glucagon further exacerbates the hyperglycemia state in type 2 DM as a result of IR and impaired insulin secretion.

Genetics also influences the pathogenesis of type 2 DM. Medical genomics is a field of active medical research with high potential for us to understand DM further. Genomic single-nucleotide polymorphisms (SMPs) have been demonstrated to be linked with DM risk.  Environmental factors may also in turn increase genetic risk in DM as with all other diseases. 

For instance, exposure to arsenic in drinking water increases the risk of type 2 DM, and so is the Bisphenol A used in hard plastic and resins shown to be linked to DM. Pesticide exposures, especially the organophosphates and chlorinated pesticides may be associated with an increased risk of DM.

We shall later in a separate write-up look at the management of DM using conventional pharmaceuticals such as metformin and glucophage the main type of biguanide among other less commonly used such as alpha-glucosidase inhibitors, biguanides, bile acid sequestrants, dopamine-2 agonists, DPP-4 inhibitors (gliptins), meglitinides (glinides), SGLT2 inhibitors, sulfonylureas and thiazolidinediones.

We shall compare these agents with a more integrative approach such as lifestyle changes, smoking cessation, exercise, diet and nutrition such as using diets low in glycaemic index involving high fibre intake, dietary fat, mind-body therapy, cognitive-behavioural therapy, biofeedback, sleep medicine, an impressive long list of natural medicine such as using coccinia cordifolia, salacia reticulata, soya, gynostemma pentaphyllum, silymarin, citrullus colocynthis, cinnamon, fenugreek, bitter melon or bitter gourd (Momordica charantia).

In Malay native medicine, they use herbs and plants which in the Malay language are called, such plants as hempedu bumi, kalmegh, Andrographis paniculata, sambung nyawa, akar sebiak, gynura procumbens, ulam raja, pokok kenikir, dukung anak, pokok gajus, belimbing buluh, belimbing asam, pokok bunga raya, kembang sepatu,misai kucing, kumis kucin. 

They also include Helminthostachys zeylanica, a herbaceous fern found in southeastern Asia and Australia, commonly known as kamraj and tunjuk-langit in Malay. 

We shall try to include nutritional supplements as well using vitamin D, chromium together with niacin (GFT), omega-3 fatty acids, magnesium, antioxidants, vitamin E, L-carnitine, benfotiamine and discuss their pharmacognosy (mode of action) together with their risks.

Benfotiamine in postprandial endothelial dysfunction has been suggested as a link between metabolic syndrome and atherosclerosis. This state is linked with oxidative stress, hyperglycaemia, hypertriglyceridemia and altered nitric oxide function as well as glucose-protein complexes in foods, glycation end products (AGEs). 

These complexes are produced at high temperatures and activate AGE-specific receptors, which in turn activates monocytes and endothelial cells and causes inflammation.

 Benfotiamine is a synthetic analogue of thiamine (vitamin B1) with very high bioavailability. It activates transketolase, the enzyme that removes AGEs, and subsequently increases postprandial endothelial.

In a small study it was shown that 350 mg of benfotiamine after a meal completely eliminated vascular measurements of postprandial endothelial dysfunction in 13 patients with type 2 DM. 

In a separate study it was shown that benfotiamine improved microalbuminuria in diabetic patients.

We may also like to have a look at the use of hormones such as incretins, a hormone produced in the small intestines that enters the vasculature and triggers the release of insulin by the pancreatic beta cells. 

We may also look at two incretins, namely glucagon-like peptides (GLP-1) and the gastric inhibitory peptide (GIP).

Scientists have discovered another class of agents that inhibits dipeptidyl peptidase-4 (DDP-4), an enzyme that degrades GLP-1 and GIP.  They have demonstrated their efficacy in increasing insulin levels and decreasing glucagon.

 However, even to summarize them, let alone to discuss them is going to be exceedingly lengthy and time consuming as I have other interests too to spend my time, such as astrophysics, mathematics, forensic science and toxicology to write also other than spending my time writing on medicine or nutrition. 

Frankly, it would be more enjoyable for me to spend my time on my hobbies such as playing my violin and flute than to simplify technical papers and summarize them for lay, but my gentle readers. For this, I thank you for your patience.  

 

But we can give this a try if given time and space.  

 

The Assessment, Criteria for High Blood Pressure: Its Conventional vs Non-Drug Approaches

 

When I was working as a Senior Medical Researcher at the Institute for Medical Research in Malaysia in the 1960’s till the mid 1990’s, we conducted thousands of health surveys among tens of hundreds of thousands of villagers and city-dwellers throughout the length and breadth of Malaysia. 

We found two most common chronic lifestyle diseases were high blood pressure and diabetes especially among the urban and city dwellers, probably due to their stress, and lifestyles, especially their dietary lifestyles. 

Even today this is the same disease scenario that overcrowds all the public hospitals. These patients who come to crowd the hospitals are not new patients who already got cured by their previous medications, but they are the same patients coming for their follow-up with the same mediccations that never cured them, followed by new patients crowding and seeking the same treatment. 

We shall first look at hypertension first as the most common disorder that afflicts most people.   

In a voluminous 1123-page 4^th edition textbook on Integrative Medicine chapters contributed by several dozen specialist clinicians, conventional as well as alternative medical specialists or combined. edited by Dr. David Rakel M, Professor and Chair of the Department Family and Community Medicine at University of New Mexico School of Medicine, Albuquerque, New Mexico, Dr. Gregory A. Plotnikoff MD, MST & Jeffery Susek, PhD have this to say together with mine.

 

Hypertension is the most important risk factor for cardiovascular morbidity and mortality in all industrialized and affluent countries. At least 65 % of the population of United States, Europe and Southeast Asian countries like Malaysia, Singapore, Philippines, especially those living in the cities have high blood pressure that place them at significantly higher risk of coronary artery disease, heart failure, renal failure, thoracic, and abnormal aneurysms, myocardial infarction and stroke. Hypertension is also associated with cognitive dysfunction, erectile dysfunction, and loss of vision. The higher the pressure the greater the risk of complications.

 

However, hypertension frequently is asymptomatic, in the absence of symptoms, elevated blood pressure may not hold particular significance for patients. In many cultures of the world, if there is no pain, there is no disease. This means that clinicians face three challenges. First, is there a shared awareness? Is hypertension even an issue for patients? Second, will the patient accept any intervention to treat an abstract number? Third, will the patient accept a long-term intervention with no immediate benefit? For these reasons, patients benefit when integrative clinicians initially explore the meanings, beliefs and interpretations the patients bring to their experience of numbers from ambulatory blood pressure measurements. The patient’s answer should both guide the clinician’s approach and foster a working partnership.

 

Hypertension prevention and treatment represents an ideal opportunity to co-develop a customized action plan that addresses options regarding diet, exercise, supplementation, smoking cessation, mind-body self-care skill development. Additional insight may also come from Ayurvedic, naturopathic and traditional Eastern medicine traditions. This individual intervention can contribute to improved health and well-being.

There is no question that every clinician must be well versed in the treatment of hypertension.  However, there is still considerable confusion regarding optimal hypertension management. For instance, in 2014 JAMA published the eight reports of the Joint National Committee on Prevention, Detection, Evaluation and the Treatment of High Blood Pressure (JNC 8). This was greatly anticipated as the previous report JNC 7 was published in 2003. Nine new recommendations were made, the most controversial of which was to redefine the goal blood pressure for those greater than 60 years of age to < 150 / 90 mm Hg For all others aged over 18 years, the goal blood pressure was recommended as < 140 / 90, preferably 120 / 80. This same goal was recommended for patients with chronic kidney disease or diabetes.

Significant confusion followed the publication of JNC 8. Critics noted the marked lack of consistency with JNC 7; the lack of consensus among the JNC 8 committee members in hypertension, with 5 of 17 authors quickly publishing a dissent, and the lack of clarity in definable quality measurement in hypertension by which to grade the physicians. The American Heart Association (AHA) and American College of Cardiology (ACC) continue to recognize JNC 7 and are currently preparing their own guidelines.

The confusion follows from the mixed conclusions of the two JNC reports. The 2003 JNC 7 reports defined a normal BP as less than 120 mm Hg, systolic and less than 80 mm Hg diastolic. The report similarly defined stage 1 hypertension as 140 – 139 mm Hg systolic and 90 -99 mm Hg diastolic. In between normal and stage 1 values is a category the JNC 7 report termed as prehypertension. This term was introduced to heighten awareness of both risk and opportunities for prevention. The JNC 7 report also noted that the BP treatment goal is less than 130 / 80 mm Hg for persons with diabetes or renal disease and hypertension. In marked contrast JNC 8 did not define a “normal” blood pressure, eliminated the stages of hypertension, and revised upwards the thresholds for treatment, including those persons with comorbidities.

How could this happen? JNC 7 recommendations were based upon experts’ consensus derived from a thorough but nonsystematic literature review that included observational studies. In contrast, JNC 8 recommendations followed from a formal systematic review by methodologies who were restricted to consideration of randomized controlled trials (RCT) with more than100 hypertensive participants who were followed for at least 1 year. This eliminated approximately 98 % of all previously published clinical studies of hypertension treatment, including observational studies, systematic reviews, and meta-analysis. The JNC 8 committee also restricted their analysis to three questions. First, does initiation of antihypertensive pharmacological treatment at specific threshold improve health outcomes? Second, do attempts to reach specific blood pressure goals lead to improvement in health outcomes? Third, do the various antihypertensive drugs or drug classes differ in regard to health outcomes? The panel did not address whether therapy-associated adverse effects harms resulted in significant changes in important health outcomes.

The JNC 8 recommendations were graded based upon the quality of evidence reviewed, Not considered for the first two questions were any RCT ‘s that included participants with a normal blood pressure such as with diabetes. Studies considered for the third question were limited to those that examined one class of medication versus another. This eliminated all single agent placebo-controlled trials from consideration.

Based upon such a rigorous evidence-based review, only the two grade A “strong” recommendations could be made. First, for those ≥ 60 years of age, antihypertensive pharmacotherapy should be initiated at threshold of ≥ 150 mm Hg systolic blood pressure or ≥ 90 mm Hg diastolic blood pressure with a goal blood pressure of < 150 mm Hg systolic and < 90 mm hg diastolic. Second, those < 60 years of age, pharmacological therapy should be initiated at a diastolic blood pressure ≥ 90 mm Hg with a treatment goal of achieving a pressure < 90 mm Hg.

Likewise, only three Grade B “moderate” recommendations could be made. Generally, including those with diabetes, initial therapy should include a thiazide diuretic, a calcium channel blocker (CCB), an angiotensin converting enzyme inhibitor (ACE), or an angiotensin receptor blocker (ARB).

Initial therapy is to advise the patient to cut down his salt (sodium) intake, followed if not successful by a thiazide diuretic to throw out excessive water that increases hydrostatic pressures or given a CCB. For those aged ≥ 18 years with chronic kidney disease, the initial or add-on pharmaceutical should be an ACE or ARB to improve kidney outcomes.

Grade C or “weak” recommendations were based upon RCT’s with major limitations, such as the presence of post hoc analysis of non-prespecified subgroups. Only the recommendation was possible for diabetics, initial therapy should be a thiazide diuretic or a CCB.

Every other recommendation made by the JNC 8 committee was labeled grade E, the category representing consensus expert opinion. This means that the evidence based on the gold standard of randomized -controlled trials was too weak to make a definitive recommendation. Further, any other clinical intervention for the prevention and treatment of hypertension fails the strictest definition of “evidence-based” practice. Given contradictory clinical trial data, these guidelines will likely remain controversial.

Although observational studies and association studies have demonstrated a strong relationship between lower blood pressure and reduced risk, all the way down to very low blood pressures, evidence from RCT’s does not indicate any patient benefit from treatment with pharmaceuticals to achieve lower blood pressures. Two significant implications exist for integrative clinicians and their patients. First, JNC 8 widens the range of acceptable blood pressures for patients. Second, JNC 8 reduces the pressure to prescribe pharmaceuticals for patients who decline or wish to avoid pharmaceuticals.

In fact, JNC 8 explicitly supports the role of conventional risk modifications including reducing sodium intake, increasing exercise, moderating alcohol consumption, weight reduction, and following the Dietary Approaches to Stop Hypertension (DASH) eating plans and nutrition.

The American Heart Association has gone even further. In 2013, it affirmed that all individuals with blood pressure > 120/ 80 mm Hg should consider trials of alternative approaches as adjuvant methods to help lower blood pressure when clinically appropriate.

Because most people wish to avoid drug therapies, clinicians in alternative approaches are often highly sought who can counsel from evidence-based regarding the most appropriate treatment option available. This is a very sound logical approach in the treatment of hypertension as in all chronic disorders, especially lifestyle diseases.

Non-drug approaches using integrative medicine are found in the JNC 8 report and they include the following:

Lifestyle non-medication such as:

1.       Smoking Cessation

2.       Nutrition and the Mediterranean Diet

3.       Olive Oil

4.       Cocoa

5.       Red Wine

6.       Omega-3 Fatty Acids

7.       Dietary Fiber

8.       Flax Seed

9.       Inorganic Nitrites

10.   Exercise

11.   Weight Loss

12.   Sleep

13.   Transcendental Meditation

14.   Dietary Supplementations

15.   CoQ10

16.   Vitamin D

17.   Magnesium

18.   Botanicals such as

19.   Garlic

20.   Hawthorn (Crataegus monogyna)

21.   Mind-Body Therapy

22.   Biofeedback

23.   Mindfulness-Based Stress Reduction

24.   Yoga

25.   Qi Gong

26.   Tai Chi

27.   Earthing

28.   Ayurveda  

29.   Traditional Chinese Medicine and East Asian Medicine

We shall discuss these therapeutic modalities which are much safer, more permanent and much more appropriate than using synthetic chemical pharmaceutical drugs that only temporarily inhibit high blood pressure and other morbidities. Drugs do more harm than ‘cure”, and does not “cure” any disease, but the patient asked to come back for the same titrated to a higher dose or replaced by another agent to repeat the same.

As discussions on these other therapeutic modalities would run into hundreds of pages, we shall stop here and put these to another day.