Anti-Aging formulation

Frank Comhaire M.D. Ph.D.

Ghent University Hospital
185, De Pintelaan
B-9000 Gent

Frank.Comhaire@ugent.be

Introduction

The most important precaution to be taken in aging people is to prevent or treat life-threatening diseases. This requires a physical "check-up" to be performed at regular intervals, by a trained (team of) physician(s). At the other hand, life style should be adapted. The lower energy requirements must be compensated by a lower calorie intake and by moderate physical exercise. Vigorous exercising is not recommended, except in trained athletes. Stress should be avoided and a possible depressive state must be diagnosed and treated.

Nutritional supplements aim at preventing common diseases including cardio- vascular disease, degeneration of the central (and peripheral) nervous system, bone demineralisation and prostate diseases. Also, "wear and tear" can be slowed down by protecting DNA against oxidative damage, by maintaining membrane fluidity, and by counteracting the damage caused by toxic agents in the environment.

Protection of the brain and Central Nervous System (CNS)

Degeneration of the brain function is related to several causes. Cerebro-vascular insufficiency, decreased metabolic activity, and inflammatory plaque formation are well-recognised mechanisms of diminished brain function, and development of dementia. The extract of Vinca Minor has successfully been used for several decades to improve blood supply to the brain (Solti et al, 1976; Hadjiev and Yancheva, 1976; Karpati and Szporny, 1976), and to enhance glucose uptake and metabolism (Tesseris et al, 1975; Vamosi et al. 1976; Matcovics et al, 1991).

Hormone replacement therapy by oestrogens or their precursors in the female and testosterone in the male has been proven to reduce inflammatory plaque formation. A similar effect can probably be obtained by shifting the phospholipid content toward Omega- 3 poly-unsaturated fatty acids. The latter can be materialised by combining the intake of fish oil, rich in Alpha-linolenic acid and Docosahexaenoic acid (DHA), with antioxidants and Vitamins B (Christophe et al, 1998).

Antioxidants

Selenium Methionine, Vit. C, Ubiquinone Q10 and Tocopherol exert strong antioxidant effects, particularly when given in a balanced proportion.

Vitamin C is water-soluble and, aside from its intrinsic antioxidant effect, regenerates Vit E. However, high concentrations of Vit C may display a intrinsic pro-oxidative effect through activation of, among others, the Fenton reaction. This will occur preferentially in persons with the haptoglobin type 2-2 or 2-1. Excessive Vit C may, therefore, exert a damaging rather than protective effect in some persons.

Antioxidant combinations can delay the oxidation of LDL cholesterol. The oxidised LDL is the initiator of vascular plaque formation. Delaying oxidation of LDL will reduce plaque formation and may prevent, or reduce atheromatosis of the blood vessels. This effect is reinforced by the supplementation with poly-unsaturated fatty acids that can decrease the level of LDL cholesterol in blood.

Ubiquinone Q10 supports contractility of the cardiac muscle. Environmental toxicants such as certain poly-chlorinated bisphenols (PCB's), dioxins and furanes inhibit the oxido-reductase activity of natural Ubiquinone. In addition, the intake of statin drugs, that are commonly used to reduce hyperlipemia, decreases the production of Ubiquinone Q10 in the liver. Hence the need to supplement this antioxidant (Navarro et al., 1998).

There are several forms of Vit E (tocopherol). The alpha-tocopherol is most commonly used (Hartman et al. 1998), but recent studies suggest that gamma-tocopherol (Giovannucci, 2000) may exert a stronger effect in detoxification (Cooney et al. 1993) and in preventing prostate cancer (Tran and Chan, 1992; Nomura et al., 1997; Heinonen et al, 1998; Chan et al.; 1999, Moyad et al. 1999, Helzlsouer et al. 2000, Freeman et al. 2000). At the other hand, excessive supply of alpha tocopherol reduces the gamma-tocopherol concentration in blood (Handelman et al. 1985; Behrens and Madere 1986; Behrens and Madere, 1987; Handelman et al. 1994).

Vitamin B

It is well known that Vit B1, B6 and B12 have a neurotrophic effect. These vitamins protect the central and peripheral nervous systems, and counteract neuropathy that commonly occurs in subclinical degree, as a result of exposure to toxic agents in the environment. In addition, Vit B directs fatty acid metabolism toward omega-3-Poly Unsaturated Fatty Acids, which have an anti-inflammatory effect and maintain fluidity of the cell membrane.

Protection of the prostate

The extract of Serenoa Repens inhibits the 5-alpha-reductase enzyme that converts testosterone to 5-alpha-dihydrotestosterone (DHT)(Weisser et al. 1996; 1997). The latter is ten times more potent an androgen than testosterone. Five-alpha-reductase activity is exceptionally high in the prostate, locally generating high concentrations of 5-alpha-DHT. Inhibition of the 5-alpha-reductase by means of Finasteride, prescribed to patients with Benign Prostate Hyperplasia, reduces the prostate volume. The extract of serenoa repens has the same effect as Finasteride (Wilt et al. 2000; Sokeland, 2000), and it has been proven to be similarly potent in reducing prostate volume in BPH patients (Romics et al, 1993; Kondas et al. 1996; Stepanov et al. 1999; Boyle et al, 2000; Vacherot et al. 2000; Bayne et al. 2000), respectively preventing BPH (Cristoni et al. 2000). In addition, the serenoa repens extract should prevent frontal male pattern hair loss (Hoffmann and Happle, 2000), similar to treatment with low dose Finasterid (Drake et al. 1999; Leyden et al. 1999; Hogan and Chamberlain, 2000; Granel, 2000); Therefore, it should be considered to prescribe serenoa repens extract in all aging men, and more particularly in those receiving hormone replacement therapy with testosterone.

Low Vit E levels in smokers have been related to an increased risk for prostate cancer (Eichholzer et al. 1999). In several large scale, double-blind and controlled trial, Vit E was shown to reduce the incidence of prostate cancer. These studies were performed with alpha-tocopherol. However, very recent data suggest gamma-tocopherol to be the most active substance in this respect. This "new player" seems to reduce the risk of prostate cancer by up to 70%. In synergism with other antioxidants, gamma-tocopherol reduces the oxidative damage to DNA. This may be the major mechanism of its anti-cancerous effect (references, see above).

Female Formulation

There is no need for a 5-alpha-reductase inhibitor in aging females, who should rather receive hormone substitution preventing menopausal symptoms and osteoporosis.

Since supplementation with oestrogens or dehydro-epi-androsterone (DHEA) adds potential risks to their proven benefits, it was decided not to use these exogenous hormones. Instead the extract of dioscorea villosa was preferred. This extract (from the root of Wild Yam) contains Sarsasapogenin and Diosgenin, the chemical structure of which is similar to that of natural progesterone (Komesaroff et al. 2001). In the adrenals, progesterone is derived from delta-5-pregnenolone that is also the precursor of DHEA via the intermediate substance 17-alpha-pregnenolone (l'Allemand and Biason-Lauber 2000). When the extract of dioscorea villosa is given, this acts as a precursor of progesterone, increasing its biosynthesis. Progesterone itself mitigates menopausal complaints, and protects against endometrial cancer. In addition, more delta-5-pregnenolone remains available for conversion into DHEA. Also, progesterone is partially converted into 17-alpha-progesterone, that is a precursor of delta-4-androstenedione. The latter is a potent precursor of testosterone and of the (weak) oestrogen: oestron, which steroids have the potential of preventing bone demineralisation and osteoporosis.

Through this interesting pathway, the extract of dioscorea villosa can influence the natural steroid hormone biosynthesis. It thus can supplement hormone deficiency in the aging female, without displaying the potentially dangerous side effects of oestradiol, because the natural regulatory mechanisms are not being overruled. This means that the natural equilibrium between progesterone, DHEA, testosterone and oestradiol remains undisturbed, while the synthetic pathway is simply activated by the natural progesterone precursor.

The palm oil incorporated into the formulation supplies tocotrienols that are effective inhibitors of both oestrogen receptor positive and -negative breast cancer cells (Guthrie et al. 1997). This interesting property of tocotrienols may grant them some value in the protection against breast cancer.

In the female formulation the extract of vinca minor has been replaced by the extract of Ginkgo Biloba that has been proven to exhibit beneficial effects on cerebral and ocular blood circulation (McKenna et al. 2001). It also enhances peripheral blood circulation and protects the sense of hearing (Reisser and Weidauer 2001). Ginkgo also has a tonifying capacity and is an antioxidant (Bridi et al. 2001).

Conclusion

Well balanced supplementation with particular vitamins and plant extracts, as well as with oil containing omega-3 poly-unsaturated fatty acids, should protect against, or at least delay the occurrence of, diseases that commonly affect the quality of life of aging persons. The immediate subjective effects of such supplementation are probably not spectacular. However, long term benefits effects can be made objective by means of sophisticated biological tests. It is the long-term effects in preventing health deterioration that are aimed at by these supplements. These, together with the implementation of essential life style adjustment, can be recommended on scientific arguments. Long term follow-up studies are needed to empirically prove the projected beneficial effects.

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