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On-line version ISSN 1806-4841
An. Bras. Dermatol. vol.85 no.1 Rio de Janeiro Jan./Feb. 2010
Milton Luiz GorzoniI; Sueli Luciano PiresII
IAdjunct Professor, Dom Pedro II Geriatric and Convalescent Hospital and the Basic Gerontology Course of the Department of Clinical Medicine, School of Medical Sciences, Santa Casa de São Paulo, São Paulo, SP, Brazil
IIProfessor, Instructor, Dom Pedro II Geriatric and Convalescent Hospital and the Basic Gerontology Course of the Department of Clinical Medicine, School of Medical Sciences, Santa Casa de São Paulo, São Paulo, SP, Brazil
The objective of antiaging medicine is to interfere in the normal human biological aging process. Is there any scientific basis to justify classifying antiaging medicine as a medical specialty and not a branch of basic biological science? This review evaluated 110 papers, nine of which (8.2% of the total) reported studies involving human subjects. Only one of these studies was randomized and double-blinded (Jadad 2). In accordance with their classification of recommendations and level of evidence, these studies were considered CII. Three of the nine articles were published in journals with an impact factor over 1.110. Therefore, there does not appear to be any solid scientific and/or clinical evidence that would justify the application of antiaging medicine in current medical practice.
Keywords: Aging; Clinical medicine; Evidence-based medicine
The basic principle of antiaging medicine, that of delaying, halting or reversing the normal human biological aging process, contradicts biogerontology, which distinguishes between aging as a natural phenomenon and the role of aging as a risk factor for certain diseases. The conduct of those who practice antiaging medicine should also be distinguished from public health-related actions for the promotion of health and disease prevention.
Organs and class associations, private and corporate medical plans and insurance companies in Brazil fail to recognize antiaging medicine as a medical specialty. Antiaging medicine focusses basically on the following areas:1
a) The reduction of oxidative stress through the use of dietary and/or mineral and/or vitamin supplements;
b) Calorie reduction and/or the use of pre- or probiotics;
c) Hormone replacement and/or supplementation;
d) Phytotherapeutic preparations;
e) Physical activity.
The basis and/or scientific evidence justifying its existence as a specialty of human medicine and not a branch of basic biological sciences are currently being questioned.
The objective of this review article was to use standardized, evidence-based scientific methodology to analyze studies published in journals in the field of human health that involve antiaging techniques, procedures and therapies, to attempt to define the level of evidence in these published studies, establish the percentage in which the methodological structure is sound and assess their applicability in current clinical practice.
To obtain the data for this paper, the following site was accessed on August 30, 2008 to search for relevant articles using the key words "antiaging medicine": http://www.nlm.nih.gov (Medline/PubMed). Articles consisting of reviews, editorials or discussions were excluded, as were descriptions of cosmetic or laboratory techniques and procedures and studies conducted in cells or animals. The studies found to have been conducted in samples of human populations were analyzed, preferably in their electronic versions and/or from their abstract on this site or on the site of the journal in which the paper was published. This analysis was based on the criteria described below:
a) In accordance with the score proposed by Jadad et al.2 that evaluates the probability of the occurrence of a study bias using seven items:
1. Was the study described as randomized or in similar terminology?
2. Was the study described as double-blinded?
3. Was withdrawal from previous drugs described?
4. Was an appropriate method for sequenced randomization described?
5. Was there a description of an appropriate double-blinding method?
6. Was the randomization method inappropriate?
7. Was the double-blinding method inappropriate?
Questions 1-5 are indicative of the quality of the study, one point being awarded for each positive answer and none in the case of negative answers. If the answers to questions 6 and 7 are affirmative, one point should be subtracted from the final score for each affirmative answer. Although this calculation does not evaluate all the elements of a study, it may be useful in making qualitative evaluations between weak (0) and strong (5 points).
b) In accordance with a summarized version of the classification of recommendations and levels of evidence defined in the Oxford Centre for Evidence-Based Medicine:3
Classification of recommendation
A: Good evidence supporting recommendation
B: Moderate evidence supporting recommendation
C: Poor evidence supporting or not supporting recommendation
Level of evidence
I - > 1 correctly controlled and randomized study.
II - > 1 clinical or case-control study or observations.
III - Clinical experience, descriptive studies or reports.
c) In accordance with the impact factor in the list of scientific journals in the Journal Citation Report - 2003 Science Edition.4
RESULTS OF THE REVIEW
The site: http://www.nlm.nih.gov (MedLine/PubMed) was accessed on August 30, 2008, using the key words "antiaging medicine" and 110 papers were identified 1,5-113, 103 of which were published entirely in English, while 7 were published in other languages (5 in Chinese, 1 in Japanese and 1 in German) with only their abstracts available in English. Their content was divided as follows:
a) Fifty-five papers (50.0% of the total) referred to reviews, editorials and discussions. 1,6,9,11-12,21,24,27,29,34,36,39-48,50-56,58,60-61,63,68,72-76,78-80,82,83,88,89,95-97,99,104,107,110,112 None of these papers consisted of systematic reviews, i.e. they were conducted in accordance with predefined criteria in an attempt to limit investigator bias. Systematic reviews frequently include meta-analyses of data from the studies evaluated in them; however, there were no cases of this type of paper.
b) One paper on the general principles of antiaging medicine 7 and five on cosmetic or laboratory techniques and procedures. 8,32-33,59,90
c) One paper could not be evaluated since not even its abstract was available electronically. Another paper was found to be unrelated to antiaging medicine.13
d) The remaining 47 papers referred principally to phytotherapeutic preparations and studies in cells, animals (ranging from insects to primates) and humans.
In this last category (human beings), 9 papers were found 14,17,25,28,30,64,67,86,109 (8.2% of the total). The principal characteristics of these papers are summarized in Table 1. Only one of these papers 109 describes the study as being randomized and double-blinded (Jadad 2), while another three 25,30,86 refer to a control group. Of a total of 8 clinical or observational studies 14,17,25,28,30,64,67,86, statistical analysis was adequately described in three papers.25,28,67
Each one of the nine papers dealt with different techniques, procedures and therapies, skin aging being the only factor in common linking four of these studies.14,28,30,67
The classification of recommendation of these nine papers 14,17,25,28,30,64,67,86,109 is considered "C" and the level of evidence "II".3
Only three of the journals in which these papers were published 28,30,109 had an impact factor over 1.110, placing them in the list of the 1,500 highest rated scientific journals according to this criterion. 114 On the other hand, two of the remaining journals had no impact factor whatsoever.25,86
COMMENTS ON THE REVIEW
Laboratory studies conducted in cells or in animals represent the first steps towards future studies and therapies in human beings. There are, however, significant distances between studies on the Drosophila melanogaster91 (fruit fly) or Musca domestica84,91 (housefly) and the immediate applicability of the findings in human beings. This would represent the most significant methodological error in antiaging medicine: inference, i.e. the extrapolation of results from basic science studies to medical practice without going through the clinical research stages.
Clinical research, also referred to as clinical trials or studies, is defined as a process of scientific investigation involving human beings. Basically, its purpose is to develop new drugs and procedures capable of having an effect on human health. Its execution requires compliance with steps defined in protocols elaborated for this purpose, based on national and international regulations. When related to the study of drugs, vaccines or diagnostic procedures, a study should be classified into one of four possible phases of clinical investigation. 115-118
a) Phase I: A drug used for the first time in normally healthy humans who generally do not have the disease for which the drug is being developed. The different routes of administration and the doses are evaluated and initial safety tests and tests to identify drug interactions are performed. Normally, the number of participants ranges from 20 to 100.
b) Phase II: Also known as a pilot study, this phase includes patients who have the disease for which the drug is being developed, the objective being to determine its safety and efficacy. Sample sizes range from 100 to 300 patients.
c) Phase III: After Phase II has been successfully concluded, the number of patients is increased in what are referred to as "amplified therapeutic or multicenter studies", in which the methodological structure is similar to that used in the previous phase. These are studies in which the duration of use is longer and the drug is compared with a placebo or with treatments that are already in use for the disease under evaluation. Their basic objective is to obtain further data, qualitatively or quantitatively, on the safety and efficacy of the drug and its interactions. If positive, the results of this phase contribute towards the registration and approval of the new drug for commercial use by the regulatory authorities. In this phase, studies evaluate between 300 and 3,000 patients.
d) Phase IV: Also known as post-marketing studies, these are conducted with the objective of evaluating the efficacy of the drug and detecting any side effects in populations using a drug that is now freely marketed to consumers who, in this phase, may number between thousands and millions.
With the exception of the study conducted by Predescu et al.109 in 343 elderly subjects, the other eight studies 14,17,25,28,30,64,67,86 reported samples ranging in size from 10 to 83 human participants, i.e. sample sizes compatible with Phase I clinical studies. Only two studies 28,64 used drugs in patients who had the disease; however, sample sizes were insufficient for the studies to be classified as Phase II. Likewise, the description of the study as being randomized or double-blind (Jadad 2) was only provided in the case of one study 109 and the use of a control group for comparative purposes was found in another three papers 25,30,86, thus raising doubts with respect to the scientific quality of these publications.
The absence of two studies coincidently dealing with the same therapy may be justified by the extent of the area of action proposed in antiaging medicine1; however, this failing also hampers the comparative analysis and duplication of the experiment, thus compromising the scientific value of findings. Even skin-aging, which was the subject of four of these papers,14,28,30,67 was evaluated using different methodologies and therapies, thereby hampering specific qualitative analysis.
The classification of recommendation "C" and level of evidence II reflect these methodological shortcomings. This also justifies the low impact factor of the majority of journals in which these papers were published.
Since the present literature review was able to identify only 9 papers referring to studies conducted exclusively in humans 14,17,25,28,30,64,67,86,109 and considering the vastness of the proposed field of action of antiaging medicine1, there is no solid scientific and/or clinical evidence that justifies its applicability in current medical practice.
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Mailing Address: Aprovado pelo Conselho Editorial e aceito para publicação em 17.04.2009. * The study was developed at the Dom Pedro II Geriatric and Convalescent Hospital and the Basic Gerontology Course of the Department of Clinical Medicine, School of Medical Sciences, Santa Casa de São Paulo, São Paulo, SP, Brazil.
Milton Luiz Gorzoni
Hospital Geriátrico e de Convalescentes Dom Pedro II
Avenida Guapira, 2674
02265 002 São Paulo SP
Tel.:/Fax: 11 2176 1204 / 5589-9408
Conflict of interest: None
The present study was part of Project No. 371/08, approved by the Internal Review Board of the Sisterhood of the Santa Casa de Misericórdia, São Paulo, SP, Brazil.
Aprovado pelo Conselho Editorial e aceito para publicação em 17.04.2009.
* The study was developed at the Dom Pedro II Geriatric and Convalescent Hospital and the Basic Gerontology Course of the Department of Clinical Medicine, School of Medical Sciences, Santa Casa de São Paulo, São Paulo, SP, Brazil.