Continuum volume 5, number 5 - mid-winter 1999

Dietetic advice for immunodeficiency

by Siro Passi and Chiara De Luca

Cell Aging Center, Istituto Dermopatico dell'Immacolata (IDI) Rome, Italy .

Dr. Siro Passi graduated in biochemistry from the University of Rome in 1969. He is head of the Cell Aging Center of the IDI Research Institute (Rome). Over the past two decades he has investigated in vivo natural defence mechanisms of living cells against reactive oxygen and nitrogen species and other toxic radicals, and has published many papers on oxidative stress and its consequences in different pathologies. On the basis of his studies of patients diagnosed HIV positive and/or with AIDS in the early '90s, he asserted that HIV phenomena are the outcome of oxidative stress, not vice versa. In 1995 he published with Prof. Ferdinando Ippolitono, a 'heretic' book, AIDS - new frontier, ed. G. Lombardo, Rome.

Chiara De Luca graduated in Biology in 1985, and Pathology in 1989. Her research has included oxidative stress in animals and plant models, inhibition of aflatoxin induced tumor development and studies on the role of lipoperoxidation in cutaneous aging. At the Cell Aging Center, she works on the role of antioxidants and polyunsaturated fatty acids in blood and tissues, and oxidative mechanisms in the induction and development of infectious, pigmentary and neoplastic pathologies. Since 1991 she has collaborated with the National Institute for Nutrition, on the prevention of mycotoxin contamination of the main components of the national diet, the determination of additives in special foods and total diets, the study of antioxidants in food and the benefits of antioxidant supplementation by the use of 'functional foods'.

Diet, by definition, is not only the food in regular use, but also a prescribed course of food designed for the treatment and prevention of diseases. Physicians of antiquity, first of all Hippocrates in Greece and Rhases in Iran, taught: "If a diet can cure, prescribe no other remedy".

With the growth of scientific knowledge, dietetics has become an applied science, and today there is an increased understanding of the role of nutritional factors in degenerative diseases, prolonged illness, acute injury, and complicated surgical and medical procedures, which are all frequently accompanied by malnutrition. The immunological disorders associated with malnutrition were named "Nutritionally Acquired Immune Deficiency Syndrome" (NAIDS), much before the trumpeting appearance of HIV. Nutrition must be considered a fundamental intervention in the early and ongoing treatment of immunodeficiency; in particular, micronutrients represent important cofactors for the optimal functioning of the immune system and are able to enhance disease resistance in humans and animals. As a consequence, a plethora of commercial dietary products and practices purporting to enhance well being or reduce weight is in vogue, mainly in advanced countries. In addition, several companies have manufactured vitamin E, b-carotene, selenium, vitamin C, superoxide dismutase capsules, Chinese herbs, multivitamin tablets, and many other microelements as a panacea for all diseases. This is surely a multi-million dollar business, but many claims are unlikely to be true. And physicians and people should be alert since some of these diets and nutrients may induce toxicity states or nutrient deficiency in individuals adhering to them. Before getting on to the subject, we take the liberty of introducing some general considerations on nutrition.

Nutrition: general considerations (1-5)

All natural foods, the composition of which is very complex, yield nutrients that, on digestion, are generally classified into proteins, lipids or fats, carbohydrates, vitamins and mineral elements. These provide the body with the compounds necessary for the production of energy in the form of work and heat, and for growth, repair and reproduction of every living cell. Carbohydrates, lipids and proteins are considered macronutrients, and are interchangeable sources of energy: lipids yield up to 9 kcal/g, protein and carbohydrates up to 4 kcal/g. Vitamins and mineral elements are considered as micronutrients.

MACRONUTRIENTS

Proteins.

Human proteins are very large molecules which represent an essential structural part of cells and are built up from the 20 "standard" amino acids, listed in Table 1, and divided into essential and non-essential amino acids. The variety of ways in which they combine can provide millions of different proteins, which are "species-specific" in that their structures differ from one species to another.

 Table 1. Essential and non-essential aminoacids in humans.

Essential	Non-essential
Histidine	Alanine
Leucine	Cysteine
Isoleucine	Glycine
Lysine	Proline
Methionine	Serine
Phenylalanine	Tyrosine
Threonine	Glutamine
Valine	Asparagine
Tryptophan	Aspartic acid
Arginine*	Glutamic acid

 

Only 10 amino acids have been shown to be "essential ", i.e. indispensable nutrients for humans and must be obtained from diet; the remaining ones can be synthesized by common intermediates, mainly deriving from the breakdown products of the metabolism of essential aminoacids.

*Even though mammals synthesize arginine by the urea cycle, the aminoacid is considered as essential, since it is required in a higher amount than can be produced by this route, mainly during normal childhood development.

Since different proteins contain different amounts of the essential amino acids, a balanced protein diet must contain different protein sources, which complement each other to supply the right proportion of all the essential amino acids. For example, milk proteins contain them in the proper proportion for a correct human nutrition; bean proteins, in contrast to wheat proteins, are rich in lysine, but are lacking in methionine. Any excess amino acids in the diet, beyond the effective needs of the body, are metabolized and burnt as a source of energy, which is largely more expensive than that deriving from fats or carbohydrates. In any case, as a general guide, it is recommended that the protein intake should be equivalent to 11-14% of the total calories in the diet.

Lipids or fats.

Lipids, partly deriving from diet, and partly from surplus carbohydrates in the food, provide the main reserve of energy. The term "lipids" includes both molecules that contain fatty acids (Table 2) - examples being triglycerides and phospholipids - and molecules such as cholesterol and steroid hormones displaying hydrocarbon ring structures. Recently, the terms "n-3 and n-6 polyunsaturated fatty acids &endash; PUFA ", in contrast with saturated fatty acids, have become very familiar to the general public. They have been associated with the concept of "healthy fat", and oils such as "evening primrose oil" or "fish oil", have been promoted by wide advertising. It is important to underline that there are no pure "saturated" or "polyunsaturated" sources of dietary fats. In fact, most food triglycerides or phospholipids contain a mixture of saturated, monounsaturated and polyunsaturated fatty acids. Thus, for example, polyunsaturated corn oil contains approximately 20 % saturated fatty acids, and saturated lard has approximately equal levels of saturated and monounsaturated fatty acids.

 Table 2. Natural fatty acids occurring in common foods, as triglycerides or phospholipids.

Common name	Main Sources
Palmitic acid (C16:0)	Palm oil, butter, cheese and other animal fats and oils
Stearic acid (C18:0)	Tallow, butter, cheese, and other animal fats and oils
Oleic acid (C18:1 n-9)	Olive and hazel oils
Linolenic acid (C18:2 n-6)	Many seed oils
a-linolenic acid (C18:3 n-3)	Linseed and rapeseed oils
g-linolenic acid (C18:3 n-6)	Borago and evening primrose oils
di-homo-g-linolenic acid (C20:3 n-6)	Human milk
Arachindonic acid (C20:4 n-6)	Animal membranes (phospholipids)
Eicosapentaenoic acid (C20:5 n-3)	Fish oils
Docosahexaenoic acid (C22:6 n-3)	Fish oils, nervous system (phospholipids)

Linoleic acid and a-linolenic acid are thought to be essential in the human diet and are known as essential fatty acids (EFA). Our cells are unable to synthesize them, and therefore they must be obtained mainly by food of vegetable origin. EFA, in the organism, can both supply energy by means of their oxidation and undergo biochemical transformations by means of desaturase and elongase enzymes to produce n-6 or n-3 polyunsaturated fatty acids (PUFA) with a higher number of double bonds, such as C20:3 n-6, C20:4 n-6, C20:5 n-3, C22:6 n-3, etc.

From a physio-pathological point of view, it has been suggested that:

n-6 PUFA may play an aetiological role in heart diseases, and cancer cells thrive on them;

n-3 PUFA may reduce the risk of both cancer and cardiovascular diseases;

monounsaturated fatty acids may help against cardiovascular diseases;

saturated fatty acids may be partly responsible for the degenerative changes in the arteries, sometimes resulting in coronary thrombosis;

trans-unsaturated fatty acids, i.e. unsaturated fatty acids with double bond in trans position, artificially generated during the process of hydrogenation of PUFA, and found in packaged snacks, may be involved in cardiovascular diseases and breast cancer.

Carbohydrates

Carbohydrates provide most of the energy (up to 90%) in almost all human diets; in any case, a well-balanced diet normally contains enough carbohydrates to provide 55-65% of total calories. The main carbohydrate in most natural foodstuff is starch that, during digestion and metabolism, is finally converted into glucose. This is carried by the blood to tissues, where it is either oxidized at once or converted to fat, since the body has a very limited capability for storing it as glycogen in muscles and liver.

MICRONUTRIENTS: vitamins and mineral elements (Table 3)

Vitamins.

Vitamins are classified as fat soluble (A, D, E and K) or water soluble (B group and C). The former ones are mainly derived from animal or vegetable fats; the vitamin B group from whole grain cereals, and vitamin C from fresh fruits and green vegetables.

Mineral elements.

The main mineral elements occurring in the body at concentration >0.005% are calcium, phosphorus, and potassium. Other elements such as iron, magnesium, sodium, zinc, iodine, copper, selenium, fluorine, cobalt, chromium occur in much lower concentrations (< 0.005 %).

Elements such as gold and silver found in the body do not appear to play a recognized metabolic role, while other elements such as barium and strontium are only suspected of being essential.

Table 3. The principal micronutrients.

THE PRINCIPAL MICRONUTRIENTS (VITAMINS & MINERALS)

 

A diet for immunodeficiency and, in particular, for diagnosed HIV seropositive (HIV+) and AIDS patients.

It is important to emphasise that it is a nonsense to believe that a single diet may be useful for all patients. In general, macro and micronutrients mentioned under "general considerations" are essential for humans, and their metabolism follows the same pathways, but the response is individual. A relationship has been shown to exist between the quality and quantity of digested nutrients and the nutritional state and the immunocompetence of an individual. There can be various "degrees" of immunodeficiency, each of which can display peculiar nutritional requirements. Therefore, we'll confine ourselves to giving dietetic advice that, in any case, can be modified during treating immunodeficiency. In our laboratory, such advice is monitored quarterly by blood analyses (plasma, lymphocytes, erythrocytes) of factors we have called "cell health indicators", i.e., albumin, free and esterified cholesterol, phospholipids and their fatty acid pattern, vitamin E, vitamin A, b-carotene, lycopene, vitamin C, uric acid, ubiquinol/ubiquinone and reduced glutathione/oxidized glutatione redox couples, total thiols, selenium, iron, copper, lipoperoxidation levels, superoxide dismutase, glutathione peroxidase, catalase, etc.^6-9. These analyses, in addition to haemochrome, CD4+, and CD8+, represent the basis of our 12-year experimental observations on patients diagnosed with AIDS, pointing out that a severe oxidative stress occurs in the blood of patients diagnosed HIV positive (HIV+) in comparison with healthy age and sex matched controls, and increases significantly with the degree of immunodeficiency: AIDS > symptomatic HIV+ > asymptomatic HIV+ > controls.

The observed oxidative stress is characterized either by the depletion of:

* lipophilic antioxidants [vitamin E (vit E), ubiquinol (CoQ₁₀H₂), ubiquinone(CoQ₁₀), vitamin A (vit A), and b-carotene],

* hydrophilic antioxidants [reduced glutathione (GSH), ascorbate, and urate],

* selenium (Se),

* phospholipids (PL) and cholesterol esters (CE), and their polyunsaturated fatty acid (PUFA) patterns,

or by an increase of:

* by-products of polyunsaturated fatty acid and protein oxidation,

or by:

* a critical imbalance ofenzymatic antioxidants (superoxide dismutase and glutathione peroxidase).

In particular, the deficiency of ubiquinol, vitamin E, reduced glutathione, phospholipids, cholesterol, and polyunsaturated fatty acids represents an early marker of the condition. It is worth mentioning that deficiency of antioxidants produces oxidative stress. When this is severe, it is able to damage cellular macromolecules, in particular, DNA; proteins, and unsaturated lipids (Table 4), and their functions, which are maintained and mediated by critical redox systems, thus contributing to the physio-pathology of many diseases (Fig.1).

Table 4

Molecule	Type of damage
DNA	Changes in adenine, guanine, cytosine, and thymine bases. Breakage of DNA backbone in single or double strand breaks of the double helix. Attack on the deoxyribose.
Unsaturated lipids	Oxidation of PUFA (lipoperoxidation) and damage to membrane proteins.
Proteins	Breakage of proteins. Oxidation of thiol and amino residues of aminoacids . Cross-linking of different protein molecules by aminoacid radicals

Table 4. Molecules damaged by a sustained oxidative stress and type of damage. An oxidative stress can be defined as any unbalance between antioxidant defences and generation of reactive oxygen and nitrogen species (ROS, RNS), and other reactive radicals (R). It follows that an oxidative stress can be induced in biological systems by the depletion of antioxidants and/or an overload of reactive oxidant species, so that the antioxidant pool becomes insufficient ^8-11.

 

  Fig.1. (view large) Possible involvement of oxidative stress in numerous diseases.

 

This does not mean that reactive oxidant species are the main cause of the above diseases. Certainly it cannot be denied that their production accompanies most, and perhaps all, human diseases, and that, in several cases, they may play a significant role in the onset of the diseases and /or contribute significantly to their progression.

The first necessary measure is to take regard of the reinstatement of those molecules, the levels of which are reduced when compared to normal, and this is possible by the opportune combination of diet and integrators.

It is enlightening that many years ago, long before the antibiotic era, there were fierce quarrels between scientists aiming to discover a drug active against Koch tubercle bacillus and scientists who, conscious that environmental factors such as poverty, deficient diet and poor housing can play an aet ological role in the incidence and spread of tubercolosis, maintained that it would be better to empower the body's defences, by reducing the influence of environmental factors. The suggestions of the latter prevailed mainly in Northern European countries. Bed rest, plentiful diet, sunlight, fresh air, adequate hygienic measures, and isolation of the patients became the regime of choice. These rational and preventive treatments led to the inversion of the spread of the disease in those countries, some decades before the discovery of streptomycin by S. A. Waksman in 1944.

What to do?

Table 3 can be considered as a useful guide for the physiological intake of micronutrients from the diet. Micronutrients does not mean nutrients of less importance as compared to macronutrients: antioxidant defences, for example, rely mainly on some vitamins and minerals from the diet. However, it is often better to utilize one or more micronutrients in the form of pills or tablets, the prerequisite being that they must be taken from natural sources and assimilated in proper amounts. An apt example is given by vitamin E (vit E). Dietary vit E occurs in a variety of forms, such as a, b, d, and g-tocopherols differing in the number of methyl groups on the chromanol ring and having a phytyl tail. The biological activities of the four homologues, as determined by a rat resorption test¹², vary from 100% for a-tocopherol (d-RRR-a-tocopherol), to 57% for b-tocopherol, (d-RRR-b-tocopherol), 31% for g-tocopherol (d-RRR-g-tocopherol), to 1.4% for d-tocopherol (d-RRR-d-tocopherol). In addition to natural homologues, synthetic vit E (d, l-a-tocopherol or all-rac a-tocopherol), which is widely used as a supplement, contains eight different isomers (SSR,SSS,SRS,SRR, RSS, RRS, RRR, RSR), of which only approximately 12% is d-RRR-a-tocopherol (Fig.2). Its stereosisomers are less biologically active (21-90 %), the biological activities of the 2-S forms being lower than the 2-R forms¹³.

In any case, despite the different biological activities of homologues and stereoisomers of a-tocopherol, there is biodiscrimination, which allows a-tocopherol to predominate in blood and tissues. Dietary or synthetic forms of vit E are absorbed from the intestinal lumen in the presence of biliary and pancreatic secretions, which are necessary for micelle formation. It has been observed that the different forms do not compete with each other during absorption and secretion in chylomicrons. In other words they are absorbed with equal affinity, and, during chylomicron catabolism, are similarly present in all of lipoproteins, an aliquot being delivered to peripheral tissues, and the remainder to liver under the form of chylomicron remnants. In contrast to the intestine, the liver discriminates among the various forms of tocopherols. In fact the hepatic tocopherol transfer protein preferentially selects and transfers d-RRR-a-tocopherol to VLDL (very low density lipoproteins) during their assembly. Following VLDL secretion into the plasma, a-tocopherol can be distributed to other lipoproteins and tissues. Excess a-tocopherol and other forms of vit E are likely excreted in the bile.

From this wide-ranging discourse on vit E and its homologues, it is possible to assert that the best way to face the real requirements of the vitamin is to administer, by any route, suitable amounts of d-RRR-a-tocopherol or of its stable derivative d-RRR-a-tocopheryl acetate.

But, let us go on with our dietetic advice.

Proteins.

60-80 g daily from different sources such as red meats, fish, whole milk, eggs, whole cereals legumes, etc. These sources must be preferentially fresh and varied. It is important to monitor quarterly patients' plasma levels of albumin, a protein containing high levels of thiols (0.3-0.5 mM) and able to scavenge a wide range of reactive species and radicals, that can damage it. Contrary to several oxidized molecules, the damaged albumin is not dangerous for the cells: it is simply removed from circulation and replaced, so that it is considered as a very important "sacrificial antioxidant".

Carbohydrates.

RDA for carbohydrates is not well defined. It is normally asserted that carbohydrates, of which approximately 90% are polysaccarides and only 10% mono and disaccarides, must provide 55-65% total body calories. In any case, at least 180g glucose/day, whatever the metabolic origin of glucose, are indispensable to satisfy the energetic requirements of both brain (140 g/day) and erythrocytes (40 g/day). Among carbohydrates, of great importance is the role of fibers, i.e. the sum of undigestible carbohydrates, such as pentosans, pectins, cellulose, emicellulose, lignine, etc. The daily consumption of fibers should be in the order of 15-20g, and derived from foods rich in fibers such as cereals, legumes, vegetables, and fruit, more than from concentrated fibers.

Lipids.

The lipid metabolism is significantly impaired in AIDS patients: phospholipids, cholesterol esters (and therefore total cholesterol), high polyunsaturated fatty acid patterns (C20:3 n-6, C20:4 n-6, C22:6 n-3, etc.) of phospholipids and cholesterol esters are significantly reduced, while saturated fatty acid patterns (C14:0, C16:0, C18:0) of the same lipid fractions are significantly increased, as compared to healthy control values (8-9). The imbalance in fatty acid patterns of n-6 and n-3 series is probably dependent on insufficient D-6, D-5, and D-4 desaturase activities^6-9, which require, for their normal physiological activities, optimal levels of vit E, ubiquinol/ubiquinone, and selenium^8-9. Brenner¹⁴, in studying the factors which influence the activity of the first of these enzymes, i.e. D-6 desaturase, demonstrated that its activity is inhibited by various causes such as ageing, reactive oxidant species, lipoperoxidation, prolonged fasting, diabetes, hypoproteic diet, alcohol, stress due to excessive release of catecholamines, thyroxine, radiations, etc. This means that a normal intake of essential fatty acids (C18:2 n-6 and C18:3 n-3) may not guarantee for their functional utilization.

From a quantitative point of view, the daily lipidic intake of fatty acids (mainly in the form of triglycerides) should be in the order of 25-30% of the total calories in the diet. Saturated fatty acids should not exceed 10%, trans-monounsaturated fatty acids 2%, monounsaturated fatty acids 10%, essential fatty acids and poly-unsaturated fatty acids 6-8%, with a ratio n-6/n-3 of 6-10/1. Also extremely important is the nutritional intake of cholesterol, and phospholipids. The former is present, mainly in free form, in cheese, milk, offal (liver, heart, kidney of beef or pork), meat, fish etc, and its daily intake should not exceed 400-500 mg. It is claimed that an elevated intake of cholesterol lowers its endogenous biosynthesis, but this homeostatic mechanism is often inefficient in many diseases. As for phospholipids, that deliver to the body not only essential fatty acids, but also fundamental molecules, such as choline, serine, and inositol, their daily intake should be in the order of 4-6g. The sources of phospholipids ought to be red meats, offal, raw vegetables, legumes, etc.

Micronutrients.

A large aliquot of vitamins and minerals is supplied by fruit and vegetables, the remainder deriving from the same sources that provide macronutrients. For example, red meats and liver from several animals, in addition to proteins, cholesterol and PUFA, are very rich in bio-available iron, contrary to spinach and egg yolk, which also contain high levels of iron. Among micronutrients, antioxidants play an important role in immunodeficiency^8,9,15-24. The purpose of the immune system is to destroy invading organisms and damaged cells, bringing about recovery. For this purpose it generates powerful substances such as cytokines and reactive oxygen species (ROS), the excessive or non-physiological production of which can be associated with mortality and morbidity after infections, and with inflammatory diseases. ROS enhance the biosynthesis of interleukin-1, interleukin-6, interleukin-8, TNF-a etc., in response to inflammatory stimuli, by activating nuclear transcription factor, NT-kB. These cytokines are able to stimulate ROS formation, that would contribute to the depletion of GSH and other antioxidants, which, directly and indirectly ought to protect the host against the damaging combined effects of ROS and cytokines. The nature and the extent of the antioxidant defences are influenced by their dietary intake or by the intake of their precursors. In particular, we have emphasized that the deficiency of lipophilic and hydrophilic antioxidants coupled to an imbalance of enzymatic antioxidant activities, affects the blood, and, consequently, tissues, of HIV+diagnosed patients, and increases significantly if the condition progresses^6-9.

Antioxidant therapies have been proposed for patients diagnosed HIV+ or with AIDS, and several clinical trials have been carried out with GSH pro-drugs (N-acetyl cysteine, glutathione esters, and oxothiazolidine-4-carboxylate) or vit C or vit E or ubiquinone or lipoic acid, etc. but, to our knowledge, without evident clinical benefits^25-33. As a matter of fact, the proposed antioxidant therapies have been nothing but antioxidant mono-therapies. They follow the dictates of literature, where it is generally reported that enzymatic and non-enzymatic antioxidants form a dynamic integral pool, in which the deficiency of one or more constituents can be compensated by the increased amounts of one or more molecules of the same pool, in order to maintain a homeostatic protective system against oxidative damage towards susceptible cell components. This may happen with a mild degree of deficiency, but not with the severe depletions and imbalances that may be observed in individuals diagnosed HIV+. It is a nonsense to 'fight AIDS' on the basis of results from experimental and highly questionable in vitro measurements, showing that an antioxidant is capable of inhibiting TNF-a synthesis or NF-kB activation and, consequently, HIV replication. Granted, for the sake of argument, that the administration of GSH pro-drugs leads to its increased intracellular levels, how is it possible to believe that such increase may re-balance the significant deficiencies of CoQ₁₀H₂, CoQ₁₀, vit E, vit A, vit C, PL, CE, PUFA, the imbalance of enzymatic antioxidants, etc.? The same is true same for vit E, or CoQ₁₀, or vit C, or lipoic acid, etc.

In our opinion, in order to re-balance the cell redox status, it is necessary to administer the deficient antioxidants by appropriate vegetables and fruit plus external supplements. Appropriate vegetables and fruit, i.e. oranges, kiwi, carrots, red grapes, apples, tomatoes, broccoli, cabbages etc. have to supply vit C, b-carotene (the precursor of vit A), lycopene, flavonoids - all antioxidants that, when administered in the form of tablets or capsules, i.e. without their natural entourage to buffer and protect them, may show pro-oxidant activities. As external supplements we intend d-RRR-a-tocopherol, ubiquinone, precursors of GSH and glutathione peroxidase, vitamin PP, the uptake of which from foods can be insufficient or not easy. In this connection, in our Cell Aging Center we have patented and produced a multinutrient preparation -IMMUGEN - recommended for the prevention and treatment of oxidative stress in all its manifestations. Each gelatine capsule (or tablet) contains:

ubiquinone, 12.5 mg; RRR-a- tocopheryl acetate, 12.5 mg; l-methionine, 50.0 mg; selenium (as selenium aspartate), 12.5 mg; soybean phospholipid complex, 147.0 mg. The phospholipid complex contains: phosphatidyl choline, 23%; phosphatidyl ethanolamine, 20%; phospatidyl inositol, 14%; phosphatidic acid, 8%; other phospholipids, 8%; glicolipids, 15%; carbohydrates, 8%; neutral lipids, 3%.

Mode of action of IMMUGEN

Reduced and oxidized ubiquinones (CoQ₁₀H₂ and CoQ₁₀ - UBI -) are ubiquitous and essential for life, meaning they exist in all body cells and support cellular energy production by helping generate adenosine triphosphate (ATP). Once UBI body levels become more than 25-30% deficient, many diseases may begin, including immunodeficiency, cancer, cardiovascular diseases, etc.

It is well known that CoQ₁₀, in addition to its function as an electron and proton carrier in mitochondria, acts as a powerful antioxidant in its reduced form ubiquinol (CoQ₁₀H₂), by preventing both the initiation and the propagation steps of lipoperoxidation in biological membranes^34-35. Furthermore, it is able to sustain efficiently the chain breaking antioxidant capacity of Vit E, by regenerating it from a-tocopheryl radical³⁶, which otherwise would need the cooperation of hydrophilic antioxidants such as Vit C and/or GSH. Therefore, as CoQ₁₀H₂ is essential to maintain Vit E status and function, decrease of CoQ₁₀H₂ in turn contributes to further exacerbate the depletion of Vit E. It is worth mentioning that CoQ₁₀H₂ is the only known lipophilic antioxidant that mammalian cells can sinthesize de novo and for which there are enzymic NAD(P)H dependent mechanisms able to (re)generate it from CoQ₁₀^37-38. A derangement of these reductive mechanisms, due to an over production of pro-oxidant reactive species, coupled to a reduced CoQ₁₀ biosynthesis, represents an important fingerprint of immunodeficiency and its progression.

RRR-a-tocopheryl acetate is a stable form of natural vit E, a chain breaking antioxidant that works in sinergy with CoQ₁₀/ CoQ₁₀H₂ to prevent oxidative damage to lipid membranes and plasma phospholipids. In its antioxidant role, vit E becomes oxidized; thereafter it can be regenerated particularly by CoQ₁₀H₂. A recent study³⁹ suggests that high serum levels of vit E in individuals diagnmosed HIV+ is associated with a decrease in risk of progression to AIDS and mortality, while low serum concentrations have been correlated with higher degree of lipoperoxidation⁴⁰, decreased plasma PUFA²², and increased p24 antigenemia²². Vit E supplementation during murine AIDS, which may be functionally similar to human AIDS modulates cytokine release and helps to ameliorate the disorders during the disease, suggesting vit E's usefulness in the treatment of AIDS in humans⁴⁰. Dietary oxidative stress due to either vit E or selenium deficiency allows a normally benign virus (amyocarditic coxackievirus B3) to convert to virulence and cause heart damage in mice. The conversion to virulence is due, according to Beck and Levander⁴¹, to a nucleotide sequence change in the genome of the benign virus, which then resembles the nucleotide sequence of virulent strains.

L-methionine, an essential amino acid, supplies both the methyl group essential for the biosynthesis of phospatidyil choline, the main membrane phospholipid, and (?) methyl transferase activity, and the sulphur atom necessary for the biosynthesis of reduced glutathione (GSH), which is the reducing molecule of glutathione peroxidase, an enzyme which also requires selenium (Se) for its antioxidant activity. Apart from polyamines, which are strong chelators of transitional metals, among the final catabolites of methionine other sulphurated molecules must also be considered, such as taurine and sulphates, which, together with GSH, are extremely valid endogenous detoxifying agents. A recent study has shown that methionine, threonine, valine and lysine are rate limiting for whole body protein synthesis in AIDS patients, suggesting that there are selective aminoacids requirements in these individuals⁴².

Selenoproteins discovered in mammalian cells may account for the important role of Se not only in the body's antioxidant defence, but also in thyroid hormone function, cellular immunity, formation of sperm, and functioning of the prostate gland. According to Cowgil a pattern does exist between the geographical distribution of Se and AIDS mortality, such that an inverse relationship persists between Se amount in the soil of an area and AIDS mortality in the same area⁴³.

Phospolipids, together with vit E, CoQ₁₀ and CoQ₁₀H₂ are essential constituents of cellular membranes, from which the immune response draws its origin.

Suggested treatment to prevent immunodeficiency progression in diagnosed HIV+ patients.

We recommend 3-4 capsules daily of IMMUGEN (or similar micronutrients) plus 50 mg of vitamin PP (the precursor of NAD(P)H) during main meals as external supplements, plus a varied diet in the home with a high biological value (Table 5). In addition we suggest food to avoid or, at least, to reduce drastically. It is evident that other supplements may be absolutely necessary, for example folate and/or vitamin B12 in the case of anemia, or vitamin B6 in psychological distress, etc.

Might the same combined treatment produce beneficial effects, for example by reducing the risks of opportunistic diseases, in diagnosed symptomatic HIV+ and AIDS patients (CD4+: < 200; 180-10 cells mm³)? The answer is undoubtedly positive in those individuals showing no serious problems of malabsorption and whose blood levels of "health cell indicators", though significantly reduced before treatment as compared to healthy controls, increase significantly after 1-2 months of treatment. When, on the contrary, oxidative stress combined with medication and recreational drug abuses, and emotional distress, have irreversibly undermined the body, leading to a downward spiral of malabsorption, weight loss, wasting, diarrhea, anorexia, body image disturbance etc., it is clear that our oral combined treatment becomes insufficient: the AIDS establishment, mercenary scientific journals and mass media can, with impunity, toast death.

 

Table 5. Dietetic advice for diagnosed HIV+ (and AIDS) patients.

BREAKFAST
Whole milk (200-300ml) or yoghurts (100-150ml); cereals (25-50g), porridge or wholemeal biscuits; soy bean lecithin (1.2 spoons); jam or honey (as sweetener); coffee or tea (optional)
MIDMORNING OR MIDAFTERNOON
Tea, biscuits, and/or fruit juice.
LUNCH OR DINNER
Pasta or rice, or soup	100-150g, daily
Bread	200-300g of whole bread or enriched bread daily
Red meat	150-200g of rare/medium steaks from beef or pork (visible fat must be removed), 2-3 times a week.
Offal	100-150g of liver or heart or kidney from beef or pork, 1-2 times a week.
White meat	200-250g of chicken or lamb or rabbit etc., 1-2 times a week
Fish	150-250g of fresh fish (cod or salmon or herring or trout. etc.,) 2 times a week.
Egg	3-4 whole eggs a week
Vegetables	150-200g daily of fresh vegetables (broccoli, lettuce, spinach, Brussels sprouts, potatoes etc.)
Legumes	100-150g of legumes (different types of beans,lentils etc.), 1-2 times a week.
Fruit	300-400g daily of fresh seasonal fruit (oranges, kiwi, black grapes, apricots,prunes, banana, etc.). Also dry fruits (nuts, almonds, raisins, dates, etc) are indicated for their high content in polyunsaturated fatty acids and potassium).
Cheese	40-50g of parmesan cheese or non-excessively fat cheese, 3-4 times a week.
Oil	Olive oil (10-30g) for prolonged cooking, non-peroxidized corn or soybean or sunflower oils for raw sauces.

In boiling vegetables, prolonged heating at high temperatures should be avoided, and the amount of water should be kept to a minimum and already hot, otherwise much of ascorbic acids and other vitamins and minerals will be destroyed or dissolved away.

Don't worry about red meats and offal: it is true they contain remarkable amounts of cholesterol (mainly free cholesterol) and iron, but cholesterol excess is the last thing an immunodeficient person need fear, because of its low plasma concentrations. As for iron and its role in pro-oxidative stress, we have ascertained that the plasma levels of ferritin and NTBI in people diagnosed HIV+ and AIDS patients are in the normal ranges (91 ± 14 ng/mL of plasma for ferritin, and 0 µg/dL for NTBI).

Table 6. Foods to avoid or reduce drastically.

Animal fat and dairy products such as butter, shortening, ordinary margarine, coconut oil, lard, cream, and food containing these ingredients, i.e., salami, sausages, wurstels, cakes, pastries, biscuits etc; fried foods, in particular from fast foods or fish and chips shops; strong spices; highly seasoned and tinned food; alcoholic beverages.

 

Abstract

Following many years of research in vivo on HIV+ and AIDS patients and on the basis of their effective blood deficiencies of micronutrients, ascertained by unequivocal analytical techniques, the authors' dietary recommendations are:

a varied diet in the home with a high biological value, which ensures an excellent intake of proteins, polyunsaturated fatty acids under the form of phospholipids and triglycerides, cholesterol, vitamins and minerals;

a cocktail of natural antioxidants and their precursors such as d-RRR-a-tocopherol, ubiquinone, selenium, precursors of GSH , to assume, as supplements, during meals.

These combined treatments, allowing a re-balancing of cell redox status, membrane lipid constituents, and possible caloric and protein deficiencies, may have a beneficial therapeutic value to prevent the progression of immunodeficiency. This is possible mainly in less compromised patients, in whom the oxidative damage to cells has not yet reached a critical threshold of no return, and can still be successfully fought. Certainly it is much healthier than the extremely toxic DNA chain terminators, anti-proteases, antibiotics, antifungal agents and similar dangerous molecules, fideistically prescribed daily by the members of the orthodox AIDS establishment, and capable of inducing a physical decline even in healthy individuals.

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Continuum volume 5, number 5 - mid-winter 1999

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