The Collison Newsletter June 2015

 

 

                 1st  INTERNATIONAL  CONFERENCE on

ANTIOXIDANTS  and  DEGENERATIVE  DISEASES*    

 

 

This conference, held in June 2015 in Kuala Lumpur, Malaysia, was hosted by the Antioxidants, Ageing and Degenerative Diseases Research Group, the National University of Malaysia (UKM) and the Faculty of Medicine, UKM.

 

The Chairman was Dr. Mohd Hanafi Ahmad Damanhuri, the Co-Chair was Prof. Dr. Suzana Makpol. At least 15 countries were represented by the more than 150 delegates who attended.

 

The following are some of the highlights of the work presented at this conference especially that which is relevant to clinical practice. Much of the content of the presentations is closely linked to my almost 200 Collison newsletters, and the message that they carry for better health, longevity and disease prevention.

 

ASSUMED KNOWLEDGE 

So that the highlights I am presenting here may be fully understood, the following section is to supply background knowledge which conference speakers assumed delegates to have.

Free Radicals and Antioxidants 

A free radical is formed when a weak bond (in a molecule), ie a shared electron, splits. Free radicals, molecules with an odd unpaired electron, are very unstable and react quickly with other compounds, trying to capture the needed electron(s) to give stability. Generally free radicals attack the nearest stable molecule, 'stealing' an electron from it. When the ‘attached’ molecule loses its electron, it becomes a free radical itself, which in turn attacks another molecule, resulting in a chain reaction. This can lead to a cascade, finally resulting in disruption of a living cell.

 

Free radicals cause damage to many components of a cell including the cell wall, mitochondria and DNA. DNA is a highly complex molecule of which our genes are composed. When enough DNA is damaged, and the telomeres shortened, cells begin to die.

Free radical damage is referred to as oxidation. The substances which protect against free radical damage (oxidation) in the body are called antioxidants. 

This subject has been fully addressed in my January 2007 newsletter Free Radicals – Antioxidants.

Oxidative Stress 

Oxidative stress is essentially an imbalance between the production of free radicals and the ability of the body to counteract or detoxify their harmful effects through neutralisation by antioxidants.

 

"Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species [free radicals] and a biological system’s ability to readily detoxify the reactive intermediates or repair the resulting damage."

 

For the past 40 years or so, oxidative stress has been increasingly recognised as a contributing factor in ageing and in various forms of pathophysiology generally associated with ageing.

There is the concept of stress sensitivity. Being highly sensitive means that stress will be felt more intensely and physiological reactions will be stronger. If you are stress sensitive, little things will get under your skin. You are disturbed by things that do not upset other people. Perhaps it is noise, waiting in lines, traffic delays and even constructive criticism. It is well recognised that stress itself is one of the strong causes of free radical formation. 

Oxidative stress increases with age.

Degenerative Diseases 

Degenerative diseases are non-infectious prevalent diseases whose incidence increases with ageing.

 

Degenerative disease can also be defined as any disease in which deterioration of structure or function of tissue occurs.

 

In addition to diabetes mellitus, there are three main groups:

  • Cardiovascular: hypertension, cardiopathies including coronary artery disease and myocardial infarction and the cerebrovascular accidents (CVA or strokes). 
  • Neoplasia disease: benign tumours and cancers. 
  • Degenerative disease of the nervous system: Alzheimer's disease and Parkinson's disease. 

 

HIGHLIGHTS from CONFERENCE PRESENTATIONS

  

Antioxidants and Metabolic Syndrome ... Prof. N. M. Ismail.

 

"The metabolic syndrome is conceptualised as a combination of metabolic and anthropometric abnormalities which include excess body fat around the waist [greater than 40 inches (100cm) for men, and 35 inches (88cm) for women], hyperglycaemia, hypertension, low concentration of HDL cholesterol and hypertrigliceridemia. It increases the risk of heart disease, stroke and diabetes."

 

Metabolic syndrome is not a disease ... It is a group of factors that carry an increased risk of degenerative diseases, especially heart disease, stroke and diabetes and their complications. For detailed information about the metabolic syndrome, see my September 2008 newsletter Metabolic Syndrome.

 

“Oxidative stress ……… is often implicated in metabolic syndrome. Oxidative stress is also associated with adiposity and insulin resistance.”

“People with metabolic syndrome have been shown to have decreased antioxidant production. Moreover, oxidative stress is implicated as the underlying pathogenesis for each component of metabolic syndrome. The close relationship of oxidative stress and metabolic syndrome suggest that oxidative stress may be involved in the pathogenesis and may also be a consequence rather than an innocent bystander. There have been reports on the possibility of metabolic syndrome patients have increased activation of biochemical pathways leading to increased delivery of reactive oxygen species [free radicals], decreased antioxidant protection and increased lipid peroxidation.” 

Metabolic syndrome affects 20-25% adults (in USA) and is associated with x2 increase in all cause deaths, x3 increase in heat attacks and x5 increase in the incidence of diabetes.

 

Oxidative stress is an important factor in obesity and diabetes.

 

Studies have shown that the antioxidant vitamins A, C and E are all low in metabolic syndrome, as are superoxide dismutase and beta-carotene levels.

 

13-19 year olds in USA have metabolic syndrome in 7% males and 3% females, all with low beta-carotene and low vitamin C levels.

 

A summary of multiple studies and trials shows that supplements of the antioxidant vitamins as well as zinc and selenium appear to be of little help.

However, positive results are demonstrated when a diet rich in antioxidants is consumed. These findings raise the question of the need for supplements. My March 2009 newsletter Foods for Health sets out the ideal diet to obtain antioxidants. 

It is important to remember that weight reduction and exercise are essential in the management of the metabolic syndrome.

 

Antioxidants in Cardiovascular Disease ... Dr. A. R. A. Rahman

 

According to WHO (2014), the leading causes of Years of Life Lost (YLL) due to premature mortality are:

  • Ischaemic Heart Disease 
  • Lower Respiratory Tract Infections 
  • Stroke.

The Foundation for Evidenced Based Medicine has indicated that, before claiming that a treatment works, the following have to be present:

  • If it works in animals, it must be proven that it also works in humans. 
  • If it works in one experiment, the result must be reproducible. 
  • There must be a clear temporal relationship between intervention and the effect produced.

With this in mind, a critical review of the literature, led to the following comment: "Based on data from intervention control trials, it is not recommended to use antioxidant vitamins supplementation to prevent or treat cardiovascular disease." For example, "Beta-carotene and vitamin E have not stood the test of time. After 7 years of follow up in the HOPE study, there was no cardiovascular benefit from vitamin E, but rather increased heart failure." [See notes re dose of vitamin E below]

 

After pointing out that beta-carotene and vitamin E do not occur singly in foods (for example, a carrot does contain beta-carotene ... but in combination with some 200 other carotenoids) the statement was made: "A Mediterranean diet, which in the U.S. is associated with a reduction in all-cause mortality is likely to contain adequate amounts of antioxidants mixed in the right proportions."

 

Antioxidants and Metabolic Disease ... Prof. N. Mustafa

 

The causes of free radicals were discussed:

  • Free radicals are produced as part of normal metabolism, especially when the immune system is fighting infection. 
  • Environmental factors: pollution, excess sunlight, toxic substances, radiation, tobacco smoke, asbestos and stress.

Diseases that are linked to free radical damage:

  • Free radicals damage low-density lipoproteins (LDL's), cell proteins and DNA. 
  • Increased risk from chronic diseases: heart disease, various cancers, diabetes, cataracts, Alzheimer's disease and Parkinson's disease.

Antioxidants:

  • Compounds that protect cells from the damage caused by oxidation. 
  • Stabilise free radicals and prevent damage to cells and tissues.

Nutrients with antioxidant properties:

  • Vitamins E, C, A
  • Selenium.

Antioxidant enzymes:

  • Superoxide dismutase which converts free radicals to less damaging substances such as hydrogen peroxide 
  • Catalase which removes hydrogen peroxide from the body 
  • Glutathione peroxidase which also removes hydrogen peroxide.

Antioxidants work:

  • By stabilising free radicals or opposing oxidation 
  • Antioxidant vitamins donate their electrons or hydrogen molecules to free radicals to stabilise them and reduce oxidative changes 
  • Antioxidant minerals act as cofactors within enzyme systems that convert free radicals to less damaging substances that can be excreted 
  • Antiatherogenesis mechanisms of antioxidant vitamins: antioxidant vitamins can inhibit the oxidation and/or uptake of LDL cholesterol. Oxidised LDL is the particularly atherogenic form of cholesterol.

Antioxidants and diabetes mellitus:

  • Prospective cohort studies have shown the intake of vitamin C significantly lowers the incidence of type 2 diabetes 
  • Three prospective observational studies have shown that alpha-tocopherol levels [but one type of vitamin E] were associated with a lower risk of diabetes 
  • Prospective studies show a higher vegetable and fruit consumption may lower the risk of developing diabetes, due to the antioxidant content of the diet.

Conclusion: "Unhealthy dietary habits and lifestyles contribute to the development of diabetes mellitus and cardiovascular disease. Studies have shown that some nutritional compounds with antioxidant and anti-inflammatory properties/effects did alter the disease process of oxidative stress-induced inflammatory disease like DM [diabetes] and CVD [cardiovascular disease]. Polyphenolic compounds such as flavonoids, isoflavones, phenolic acids and lignam contribute to increased plasma antioxidant capacity, decreased oxidative stress markers and reduced total and LDL cholesterol. ……… Antioxidants are suitable choices for the prevention or treatment of metabolic syndrome-based cardiovascular diseases or diabetes mellitus, but more randomised clinical trials need to be performed."

 

Synergistic Effects of Omega-3 Polyunsaturated Fatty Acids in Chemoprevention and Chemotherapy ... Prof. H-K Na

 

"Omega-3 polyunsaturated fatty acids, such as docosahexaenoic acid (DHA) and eicosapentanoic acid (EPA), have been reported to possess anti-oxidant, anti-inflammatory, and chemopreventive properties.  …. According to a randomised double blind trial, cancer patients who consumed omega-3 fatty acids as a supplement showed better weight gain and increases in the lean body mass than the individuals without intake of omega-3 fatty acids."

 

Modulation of Redox Balance by Antioxidants in Carcinogenesis ... Prof. A-N. T. Kong

 

Redox reactions include all chemical reactions in which atoms have their oxidation state changed; in general, redox reactions involve the transfer of electrons. The term 'redox' comes from two concepts involved with electron transfer: reduction and oxidation. Oxidation is the loss of electrons or an increase in oxidation state. Reduction is the gain of electrons or a decrease in oxidative state.

 

"Diverse dietary and herbal medicinal phytochemicals are capable of promoting human heath and prevention of diseases including neurological and cancer. These phytochemical "antioxidants" can counteract oxidative stress which is caused by an imbalance of reactive oxygen species (ROS)/reactive nitrogen species (RNS) and the antioxidative stress defence systems in cells. ROS/RNS or carcinogen metabolites can attack intracellular proteins, lipids, and nucleic acids, resulting in epigenetic modifications, genetic mutations, carcinogenesis and other diseases."

 

"Healthy compounds isolated from fruits, vegetables, teas, and herbs include:

  • Tea polyphenols - green and black tea 
  • Resveratrol - grapes, red wine, almond skin 
  • Isothiocyanates - broccoli, cauliflower, Brussel sprouts 
  • Lycopene and flavonoids - tomatoes 
  • Omega-3 fatty acids - fish oil and krill oil 
  • Diallyl sulfide - garlic 
  • Curcurmin - spices.

All these give protection against cancer, cardiovascular disease, inflammatory disease, and metabolic disease. There are many (thousands) of dietary phytochemicals and natural compounds that have been isolated from fruits, vegetables, and herbs."

 

In summary, dietary/herbal phytochemicals would confer protection against diseases such as cancer, especially in the early stages.

 

My January 2010 newsletter Phytochemicals gives a detailed discussion of these important antioxidants.

 

Antioxidants in Degenerative Diseases: Special Focus on Honey ... Prof. A. H. Gam

 

"Honey is the only insect-derived natural product with therapeutic, traditional, spiritual, nutritional, cosmetic, and industrial value."

 

The health benefits of honey have been detailed in my June 2011 newsletter Honey - Health Benefits. Item 3 listed under the health benefits addresses honey's role as an antioxidant.

 

In this presentation, the author described in detail the classification of polyphenols, highlighting flavonoids, which are the largest group of polyphenols with more than 2000 individual flavonoids known. Phytochemicals is a broad term describing a wide variety of compounds produced by plants: polyphenols, antioxidants, flavonoids, phytonutrients, flavones, isoflavones, catechins, anthocyanidins, carotenoids and allyl sulfides being some of the names for phytochemicals.

 

Malaysian Tualang honey was studied extensively. It has similar antibacterial properties to Manuka honey (from New Zealand), known to have very high antibacterial properties. When compared to two other Malaysian honeys, the Tualang honey had the highest antioxidant properties.

 

Six phenolic acids have been identified in Tualang honey:

  • Gallic 
  • Syringic 
  • Benzoic
  • Trans-cinnamic 
  • Coumarin 
  • Caffeine acids.

Five flavonoids have also been identified:

  • Catechin 
  • Kaempferol 
  • Naringenin 
  • Luteolin 
  • Apigenin.

Also, 35 volatile constituents were identified. It was concluded that Tualang honey has antibacterial and antiproliferative properties, with renal, hepatic, and cardiac protective properties.

 

It is suggested that honey, especially Royal Jelly (a honey bee secretion that is used in the nutrition of larvae, as well as adult queens) may protect against telomere shortening (and so increase life span), as the telomere length in queen bees is not shortened as she ages. For further information about telomeres see my August 2010 newsletter Telomeres.

 

"Honey and honey bee products have strong antioxidant potential due to their constituents which act synergistically and have the potential to be coupled with modern therapies."

 

Extension of the Health-span by Antioxidants: True or False? ... Prof. Y. Yonei

 

"The goal of anti-ageing medicine is to promote healthy daily living, improve quality of life and thereby achieve healthy longevity, not merely lifespan extension."

 

The risk factors for not achieving this include: oxidative stress, glycemic stress, psychosomatic stress, immunologic stress, and poor lifestyle. The most significant factor should be determined and set as a primary goal of treatment. The risk factor varies amongst individuals.

 

"Medical care aimed at achieving healthy longevity should be provided for each patient according to a personalised anti-ageing treatment plan based on the appropriate ageing assessment."

 

The evaluation of ageing requires assessment of 'functional age': muscle age, vascular age, neural age, hormone age and bone age. It also must take into account the 'risk factors': immune stress, oxidative stress, mental stress, lifestyle, glycemic stress or metabolic stress.

 

Massive free radical formation results from: exhaust gasses from vehicles, alcohol, tobacco smoking, UV sunlight excess, mental stress, food additives, and agriculture chemicals. These must be avoided as part of prevention of free radical formation. It is also necessary to increase anti-oxidative capacity by the consumption of antioxidants and detoxification.

 

The Human Anti-Oxidant Network was summarised:

  • Prevention: superoxide dismutase, catalase, peroxidase 
  • Free radical scavenging: vitamins A, C, E, co-enzyme Q10, alpha-lipoic acid, food derived antioxidants such as catechins, polyphenols, astaxanthin, lycopene etc. 
  • Repairing: phospholipase, protease, transferase, DNA repairing.

"It is sure that the antioxidant therapy is effective in the individuals with high oxidative stress. Our data of serum antioxidant concentrations revealed that antioxidants are not completely balanced in the most cases in which you find insufficiency. So, my answer is that "Extension of Health-span by Antioxidants" may be true if cases are adequately selected. However, from my experience involved with the clinical trials of antioxidants, results are variable, showing sometimes effective while sometimes ineffective. In conclusion, we need to learn about the defence system against oxidative stress and both shortage and excess risks of antioxidants, and also to judge the degree of oxidative stress in individuals, so that we can achieve health-span extension by antioxidants."

 

Antioxidant Vitamins and Cancer Prevention: is it Still Relevant? ... Prof. P. Sylvester

 

"Antioxidant vitamins regulate peroxidation reactions and free radical production. Uncontrolled or excessive free radical production can ultimately lead to cellular damage, dysfunction, or death. Furthermore, free radicals are highly reactive and have the potential to form DNA adducts that can lead to gene mutation and the initiation of cancer. Some antioxidants can be produced naturally by the body, while antioxidant vitamins must be obtained from the food or dietary supplements. Numerous laboratory studies using cell culture and animal experimental models have shown that antioxidant vitamins can prevent free radical damage and reduce the risk of various types of cancer."

 

"However, clinical studies in humans have produced conflicting results. There is also a great concern that antioxidant supplements may reduce the creation of free radicals produced by radiotherapy and chemotherapy, and thereby interfere with the effectiveness of these treatments. In contrast, other evidence suggests that oxidation supports the growth of malignant cells and antioxidants will reduce the promotional effects of oxidation in the malignancy process. These studies strongly suggest that antioxidants should be administered with chemotherapy because oxidative stress initiates and promotes cancer, and cancer patients often have low levels of antioxidants, which would increase their susceptibility to the adverse side effects and cytotoxicity associated with traditional radiation and chemotherapy."

 

"A great deal of evidence has also accumulated demonstrating that many antioxidant vitamins display multiple mechanisms of action that are independent of their antioxidant potency, and depending on the dose administered, these vitamin antioxidants can modulate gene expression and signal transduction pathways involved with cancer cell proliferation and survival, as well as influence the process of apoptosis and inflammation."

 

One interesting study was quoted in an attempt to solve the conflicting evidence of the efficacy of vitamin E. It would appear that the dose is relevant: less than 400iu per day showed beneficial results and the negative or no benefit from taking vitamin E were above this dose. In this example, more is not better. Paracelsus said: "Sola dosis facit venenum" - The dose makes the poison. "All things are poison and nothing is without poison; only the dose makes a thing not a poison". Vitamin E illustrates this basic principle of toxicology. High dose of vitamin E became oxidative, thus causing harm.

 

Part of Professor Sylvester’s conclusion was: "Evidence suggests that synthetic or isolated antioxidants are less effective than those naturally found in food. Whole food sources are better than processed food. Fresh fruits, vegetables, nuts, whole grains, and legumes are full of phytonutrients with multiple beneficial effects."

Other Points of Interest Raised in Some of the Presentations and Question Time 

1.             Tocotrienols are members of the vitamin E family. Vitamin E is made up of four tocopherols alpha, beta, gamma, and delta. Tocotrienols are crucial components of the entire spectrum of vitamin E with their own unique health benefits: they inhibit cholesterol production in the liver and suppress hepatic HMC-CoA reductase activity that results in the lowering of LDL cholesterol levels. They naturally occur in high concentrations in Palm oil. Unfortunately many studies use only one type of vitamin E, for example, alpha tocopherol.

 

2.             Plant growth is limited by minerals with those shortest supply.

 

3.             The cost of development of a new drug to market:

A new report by the Tufts Centre for the Study of Drug Development (CSDD) pegs the cost of developing a prescription drug that gains marketing approval at US$2.6 billion, a 145% increase, correcting for inflation, over the estimate the Centre made in 2003.

 

Forbes (www.forbes.com), in analysing the different pharmaceutical companies, puts a much higher cost. The following are the figures for three companies.

Pfizer inc.  14 drugs. R and D $7.727 billion per drug.

AstraZeneca. 5 drugs. R and D $11.790 billion per drug.

Eli Lilly. 11 drugs. R and D $4.577 billion per drug.

The total Research and Development spending in 1997-2011 was:

Pfizer $108.178 billion.

Astra $58.955 billion.

Eli Lilly $50.347 billion.

"The drug industry has been tossing around the $1 billion number for years. The range of money spent is stunning. The main expense is failure." Astra brought to market only 5 in that period, hence the highest cost per drug. 

4.             Is cancer a disease of older people?

 

Taking breast cancer as an example:

 

Breast cancer cell division can broadly be divided into slow, intermediate and fast.

    • Fast cell division (fast growing cancer): doubles every 60 days. From the first cancer cell, the cancer is 'ducal cancer in situ' (DCIS) for 4 years. It takes 7 years to be 1mm in diameter, 9 years to be 1cm, and 10 years to be 2cm. 
    • Intermediate cell division: doubles every 120 days. From the first cancer cell, the cancer is DCIS for 7 years. It takes 15 years to be 1mm in diameter, 18 years to be 1cm, and 20 years to be 2cm. 
    • Slow cell division (slow growing cancer): doubles every 180 days. From the first cancer cell, the cancer is DCIS for 10 years. It takes 22 years to be 1mm, 26 years to be 1cm, and 30 years to be 2cm. (Prof. P. W. Sylvester)

Prevention of cancer should be started as early (as young) as possible, since the cancer may well be present for a decade or more before it becomes clinically recognisable. It may well be that such 'prevention' is actually therapeutic. Although breast cancer is given here by way of example, it should be noted that different cancers have different rates of cell division.

 

Recommendations for the prevention of cancer are set out in a 537 page report by the World Cancer Research Fund, in association with the American Institute for Cancer Research. There were 8 main recommendations and 2 special recommendations by way of summary. These have been reproduced, with commentary, in my March 2008 newsletter Prevention of Cancer. Food, Nutrition, Physical Activity and the Prevention of Cancer.

 

In Summary

The above selected summaries are relevant to clinical practice and healthy lifestyle and, in particular, both the prevention of and treatment of degenerative disease. 

Live longer, yes! But quality of life is more important.

 

*Copyright 2015: The Huntly Centre.

Disclaimer: All material in the huntlycentre.com.au website is provided for informational or educational purposes only. Consult a health professional regarding the applicability of any opinions or recommendations expressed herein, with respect to your symptoms or medical condition.

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