Gli integratori? fanno venire il cancro

[Dora]

l trial, è stato sospeso perché si è visto non solo che i pazienti in ART non avevano nessun beneficio dall'assumere alte dosi di vitamine (né una riduzione del rischio di progressione dell'infezione, né un innalzamento dei CD4, né una diminuzione della viremia) ma, per di più, molti di loro hanno avuto un innalzamento fino a 5 volte delle transaminasi.

Ma che dosi di cavallo prendevano questi americani?
A me le transaminasi sono calate.

Il trial si è svolto in Tanzania e questo rende ancora più importanti i suoi risultati.

Mi sembra strano che ti sia sfuggito, perché è vero come dice Nathan che la stampa generalista non ha dedicato nessuno spazio a questa ricerca (e temo che lui abbia ragione a credere che ci sia un pregiudizio favorevole alle vitamine), ma è anche vero che tutti i siti importanti che si occupano di HIV l'hanno segnalata.

Per esempio, oltre ad aidsmap, che ho citato nel mio post, anche:

• - HivandHepatitis: High-dose Vitamins Do Not Improve HIV Outcomes or Lower Mortality, but May Harm Liver;
  - The Body: Multivitamins Won't Boost Standard HIV Care, Study Finds;
  - Paul Sax ha scritto addirittura due post: 1) It’s Time to Tell Our Patients to Stop Their Vitamin Supplements e 2) Vitamins and the Department of Bad Timing.

[skydrake]

Volevo porre l'accento su "taking high doses of multivitamin supplement"

Scommetto che se uno raddoppia o triplica anche le dosi della propria HAART, finisce conciato abbastanza male.

Non ho acceso al full article e quindi non posso approfondire cosa intendono per High.

[Dora]

Scommetto che se uno raddoppia o triplica anche le dosi della propria HAART, finisce conciato abbastanza male.

Una scommessa troppo facile: come diceva Uffa tempo fa, non stiamo parlando di uranio impoverito, quando parliamo di vitamine.

Non ho acceso al full article e quindi non posso approfondire cosa intendono per High.

Da S Isanaka, F Mugusi, C Hawkins, et al. Effect of High-Dose vs Standard-Dose Multivitamin Supplementation at the Initiation of HAART on HIV Disease Progression and Mortality in Tanzania: A Randomized Controlled Trial. JAMA 308(15):1535-1544. October 17, 2012:

• (...) Despite the substantial health benefits resulting from HAART, there are certain limitations to its efficacy— immune reconstitution may not be complete or sustained and the risk of opportunistic infection and death can remain high. In addition, antiretroviral therapy (ART) is associated with toxic adverse effects contributing to increased morbidity and decreased quality of life.
  To maximize the benefits of HAART, the provision of adjuvant treatments may be considered.
  Multivitamins are key factors in maintaining immune function and neutralizing oxidative stress and could play an important role in reducing morbidity associated with HIV disease and treatment.
  Among individuals not receiving HAART, 2 large randomized trials have demonstrated that high doses of B-complex vitamins, vitamin C, and vitamin E with and without other micronutrients reduced the risk of morbidity and mortality due to HIV.
  Among patients receiving HAART, the evidence is mixed. Several small randomized studies suggest a potential benefit of high-dose vitamin supplementation on immunological and virological end points. However, limited by small samples and short follow-up, these studies remain insufficient to determine whether prolonged high-dose multivitamin supplementation in the context of HAART is safe and can improve clinical outcomes.
  
  We have previously shown that highdose multivitamin supplementation compared with placebo reduced the risk of HIV disease progression and increased CD4 counts among women infected with HIV not receiving HAART.
  To test the hypothesis that high-dose multivitamin supplementation compared with standard-dose supplementation decreases the risk of HIV disease progression or death and improves immunological, virological, and nutritional parameters in patients infected with HIV receiving HAART, we conducted a double-blind, randomized controlled trial of multivitamin supplementation (including vitamin B complex, vitamin C, and vitamin E) in adults initiating ART in Dar es Salaam,
  Tanzania. A single level of the recommended dietary allowance (RDA) was provided as the comparator regimen, rather than placebo, to increase the generalizability of our findings to patients in developed and developing countries where a standard RDA multivitamin supplement may be consumed.

I risultati sono ampiamente segnalati e discussi negli articoli che ho linkato nei miei post precedenti, quindi non li riporto; ma possono essere sintetizzati così:

[Dora]

Nathan Geffen ha raccolto in un post una serie di considerazioni sulla questione dell'integrazione di vitamine e micronutrienti in persone con HIV. In attesa che (a breve) esca un suo lavoro più approfondito, questo è il post che ha scritto per Quackdown.info (...)

L'articolo di Nathan Geffen su High dose multivitamin use in advanced HIV has no benefit to CD4 and viral load and may cause liver toxicity è stato pubblicato la settimana scorsa su I-base. La parte iniziale descrive il lavoro uscito su JAMA di cui abbiamo già parlato. Riporto quindi soltanto il suo "commento".

• This trial is a setback for proponents of high-dose supplementation. At best there was no benefit (or perhaps a reduced rate of neuropathy, though the prevalence of neuropathy in both arms remained alarmingly high) and at worst a potentially negative impact on liver enzymes (though non-significant at a clinically relevant level).
  
  A more compelling study for the benefits of micronutrient supplementation was published in 2004 in the New England Journal of Medicine by Wafaie Fawzi of Harvard Medical School and his colleagues. [2] In this randomised placebo-controlled trial, 67 of 271 pregnant women who received a supplement containing vitamins B, C and E progressed to WHO stage 4 or died compared to 83 of 267 women who received placebo (24.7% vs. 31.1%; RR:0.71; 95%CI: 0.51-0.98; p=0.04).
  
  The multivitamin arm participants also had significantly higher CD4 and CD8 cell counts and significantly lower viral loads. Interestingly, the study found that adding vitamin A to the regimen reduced its benefit. The quality of this study was high but the targeted population was very specific, i.e. pregnant women in a very poor country. Recommending micronutrient supplementation to people with HIV or even only pregnant women with HIV cannot be generalised on the basis of this study alone.
  
  However, a Cochrane Review published in March 2012 considered 78 clinical trials of antioxidants that included nearly 300,000 patients. [3] The authors concluded that the “current evidence does not support the use of antioxidant supplements in the general population or in patients with various diseases.” They also wrote, “Beta-carotene and vitamin E seem to increase mortality, and so may higher doses of vitamin A. Antioxidant supplements need to be considered as medicinal products and should undergo sufficient evaluation before marketing.”
  
  Four relevant Cochrane Reviews have been conducted on vitamins and HIV:
  
  Sinclair and colleagues (November 2011) considered 23 trials with over 6,800 patients that examined nutritional supplements for people with TB. They concluded that there was not enough evidence to judge whether multivitamins reduced mortality in HIV negative people with TB, but found moderate quality evidence that they had little or no effect in people co-infected with HIV. [4]
  Van den Broek and colleagues considered vitamin A supplementation during pregnancy and examined 31 trials, of which 14 were included in their analysis. They published in March 2011. Overall, vitamin A supplementation did not reduce maternal mortality, perinatal and newborn mortality, stillbirth, preterm birth, low birthweight or newborn anaemia. They did however find good evidence that vitamin A deficiency is common. The evidence also suggested a reduction in maternal infection, but the authors wrote that these data were not of a high quality. [5]
  Siegfried and colleagues published a review earlier this year that considered four trials in pregnant women and their infants. They concluded that micronutrient supplements improved the health of pregnant women and their infants. They also wrote that no significant adverse effects were reported. However, zinc supplementation did not show any significant benefits. They found that selenium did not benefit mothers HIV progression or their pregnancy but may increase the likelihood of a child surviving and may reduce diarrhoea in mothers. They found insufficient evidence about the effects of supplements on pregnant women living with HIV who were on antiretroviral medicines. [6]
  The same authors published another review in January 2012 that updated an earlier review they did in 2005 titled, “Micronutrient supplementation for children and adults with HIV infection”. Their findings are quite nuanced. They reviewed 30 trials involving over 22,000 participants. Of these, 20 trials examined single supplements (vitamin A, vitamin D, zinc, selenium) and 10 examined multiple micronutrients. Eight trials were in children. [7]
  Vitamin A had no benefit in adults, but halved all-cause mortality in a meta-analysis of three trials in African children.
  
  Zinc supplements reduced diarrhoea in one trial of South African children, but showed no benefits to adults in a trial of Tanzanian women or Peruvian adults with persistent diarrhoea.
  
  The authors found that selenium reduced diarrhoea in pregnant women in Tanzania, and reduced viral load in two separate small trials in American adults.
  
  Vitamin D showed no benefits when taken alone. They cited the Tanzanian trial described above as evidence for benefit to pregnant women and their children. They also found another Tanzanian trial in which supplements reduced the recurrence of pulmonary TB and increased weight gain in co-infected patients.

References:

2) Fawzi W et al. A Randomized Trial of Multivitamin Supplements and HIV Disease Progression and Mortality. N Engl J Med 2004; 351:23-32July 1, 2004. DOI: 10.1056/NEJMoa040541
http://www.nejm.org/doi/full/10.1056/NEJMoa040541

3) Bjelakovic G et al. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Review March 2012.
http://summaries.cochrane.org/CD007176/ ... s-diseases

4) Sinclair D et al. Nutritional supplements for people being treated for active tuberculosis. Cochrane Review November 2011.
http://summaries.cochrane.org/CD006086/ ... berculosis

5) Van den Broek N et al. Vitamin A supplementation during pregnancy for maternal and newborn health outcomes. Cochrane Review March 2011.
http://summaries.cochrane.org/CD008666/ ... h-outcomes

6) Siegfried N et al. Micronutrient supplementation interventions to reduce harm in pregnant and lactating women living with HIV. Cochrane Review March 2012.
http://summaries.cochrane.org/CD009755/ ... -with-hiv-_

7) Irlam JH et al. Micronutrient supplementation for children and adults with HIV infection. Cochrane Review January 2012.
http://summaries.cochrane.org/CD003650/ ... -infection

[Dora]

Ben quattro articoli sugli Annals of Internal Medicine usciti ieri dedicati al fallimento dei trial sull'integrazione con vitamine della dieta di persone nei Paesi sviluppati (per chi soffre di malnutrizione o malassorbimento dei nutrienti il discorso è ovviamente più complicato):

• - High-Dose Multivitamins and Minerals After a Heart Attack
  - Oral High-Dose Multivitamins and Minerals After Myocardial Infarction: A Randomized Trial
  - Long-Term Multivitamin Supplementation and Cognitive Function in Men: A Randomized Trial
  - Vitamin and Mineral Supplements in the Primary Prevention of Cardiovascular Disease and Cancer: An Updated Systematic Evidence Review for the U.S. Preventive Services Task Force

E, di fronte a tale enorme massa di dati che smentiscono una qualsiasi utilità degli integratori a base di vitamine e minerali per prevenire infarto, cancro, demenza e compagnia bella, non poteva ovviamente mancare un editoriale in cui si reclama la necessità di piantarla di buttare denaro in qualcosa che non solo non fa bene, ma in certi casi può addirittura far male:


Enough Is Enough: Stop Wasting Money on Vitamin and Mineral Supplements (Il full text su cortesia di J.Levin)

Eliseo Guallar, MD, DrPH; Saverio Stranges, MD, PhD; Cynthia Mulrow, MD, MSc, Senior Deputy Editor; Lawrence J. Appel, MD, MPH; and Edgar R. Miller III, MD, PhD

Three articles in this issue address the role of vitamin and mineral supplements for preventing the occurrence or progression of chronic diseases. First, Fortmann and colleagues (1) systematically reviewed trial evidence to update the U.S. Preventive Services Task Force recommendation on the efficacy of vitamin supplements for primary prevention in community-dwelling adults with no nutritional deficiencies. After reviewing 3 trials of multivitamin supplements and 24 trials of single or paired vitamins that randomly assigned more than 400 000 participants, the authors concluded that there was no clear evidence of a beneficial effect of supplements on all-cause mortality, cardiovascular disease, or cancer.

Second, Grodstein and coworkers (2) evaluated the efficacy of a daily multivitamin to prevent cognitive decline among 5947 men aged 65 years or older participating in the Physicians’ Health Study II. After 12 years of follow-up, there were no differences between the multivitamin and placebo groups in overall cognitive performance or verbal memory. Adherence to the intervention was high, and the large sample size resulted in precise estimates showing that use of a multivitamin supplement in a well-nourished elderly population did not prevent cognitive decline. Grodstein and coworkers’ findings are compatible with a recent review (3) of 12 fair- to good-quality trials that evaluated dietary supplements, including multivitamins, B vitamins, vitamins E and C, and omega-3 fatty acids, in persons with mild cognitive impairment or mild to moderate dementia. None of the supplements improved cognitive function.

Third, Lamas and associates (4) assessed the potential benefits of a high-dose, 28-component multivitamin supplement in 1708 men and women with a previous myocardial infarction participating in TACT (Trial to Assess Chelation Therapy). After a median follow-up of 4.6 years, there was no significant difference in recurrent cardiovascular events with multivitamins compared with placebo (hazard ratio, 0.89 [95% CI, 0.75 to 1.07]). The trial was limited by high rates of nonadherence and dropouts.

Other reviews and guidelines that have appraised the role of vitamin and mineral supplements in primary or secondary prevention of chronic disease have consistently found null results or possible harms (5–6). Evidence involving tens of thousands of people randomly assigned in many clinical trials shows that β-carotene, vitamin E, and possibly high doses of vitamin A supplements increase mortality (6–7) and that other antioxidants (6), folic acid and B vitamins (8), and multivitamin supplements (1, 5) have no clear benefit.

Despite sobering evidence of no benefit or possible harm, use of multivitamin supplements increased among U.S. adults from 30% between 1988 to 1994 to 39% between 2003 to 2006, while overall use of dietary supplements increased from 42% to 53% (9). Longitudinal and secular trends show a steady increase in multivitamin supplement use and a decline in use of some individual supplements, such as β-carotene and vitamin E. The decline in use of β-carotene and vitamin E supplements followed reports of adverse outcomes in lung cancer and all-cause mortality, respectively. In contrast, sales of multivitamins and other supplements have not been affected by major studies with null results, and the U.S. supplement industry continues to grow, reaching $28 billion in annual sales in 2010. Similar trends have been observed in the United Kingdom and in other European countries.

The large body of accumulated evidence has important public health and clinical implications. Evidence is sufficient to advise against routine supplementation, and we should translate null and negative findings into action. The message is simple: Most supplements do not prevent chronic disease or death, their use is not justified, and they should be avoided. This message is especially true for the general population with no clear evidence of micronutrient deficiencies, who represent most supplement users in the United States and in other countries (9).

The evidence also has implications for research. Antioxidants, folic acid, and B vitamins are harmful or ineffective for chronic disease prevention, and further large prevention trials are no longer justified. Vitamin D supplementation, however, is an open area of investigation, particularly in deficient persons. Clinical trials have been equivocal and sometimes contradictory. For example, supplemental vitamin D, which might prevent falls in older persons, reduced the risk for falls in a few trials, had no effect in most trials, and increased falls in 1 trial. Although future studies are needed to clarify the appropriate use of vitamin D supplementation, current widespread use is not based on solid evidence that benefits outweigh harms (10).

With respect to multivitamins, the studies published in this issue and previous trials indicate no substantial health benefit. This evidence, combined with biological considerations, suggests that any effect, either beneficial or harmful, is probably small. As we learned from voluminous trial data on vitamin E, however, clinical trials are not well-suited to identify very small effects, and future trials of multivitamins for chronic disease prevention in well-nourished populations are likely to be futile.

In conclusion, β-carotene, vitamin E, and possibly high doses of vitamin A supplements are harmful. Other antioxidants, folic acid and B vitamins, and multivitamin and mineral supplements are ineffective for preventing mortality or morbidity due to major chronic diseases. Although available evidence does not rule out small benefits or harms or large benefits or harms in a small subgroup of the population, we believe that the case is closed— supplementing the diet of well-nourished adults with (most) mineral or vitamin supplements has no clear benefit and might even be harmful. These vitamins should not be used for chronic disease prevention. Enough is enough.




Un articolo anche su MedPage Today di ieri: Two More Studies Slam Multivitamins

[uffa2]

Scommetto che se uno raddoppia o triplica anche le dosi della propria HAART, finisce conciato abbastanza male.

Lo scommetto pure io Sky
Però, siamo onesti, fosse solo perché una pastiglia di Atripla costa 36€, mi pare difficile cadere in una simile tentazione.

[skydrake]

Scommetto che se uno raddoppia o triplica anche le dosi della propria HAART, finisce conciato abbastanza male.

Una scommessa troppo facile: come diceva Uffa tempo fa, non stiamo parlando di uranio impoverito, quando parliamo di vitamine.

Non ho acceso al full article e quindi non posso approfondire cosa intendono per High.

Da S Isanaka, F Mugusi, C Hawkins, et al. Effect of High-Dose vs Standard-Dose Multivitamin Supplementation at the Initiation of HAART on HIV Disease Progression and Mortality in Tanzania: A Randomized Controlled Trial. JAMA 308(15):1535-1544. October 17, 2012:

• (...) Despite the substantial health benefits resulting from HAART, there are certain limitations to its efficacy— immune reconstitution may not be complete or sustained and the risk of opportunistic infection and death can remain high. In addition, antiretroviral therapy (ART) is associated with toxic adverse effects contributing to increased morbidity and decreased quality of life.
  To maximize the benefits of HAART, the provision of adjuvant treatments may be considered.
  Multivitamins are key factors in maintaining immune function and neutralizing oxidative stress and could play an important role in reducing morbidity associated with HIV disease and treatment.
  Among individuals not receiving HAART, 2 large randomized trials have demonstrated that high doses of B-complex vitamins, vitamin C, and vitamin E with and without other micronutrients reduced the risk of morbidity and mortality due to HIV.
  Among patients receiving HAART, the evidence is mixed. Several small randomized studies suggest a potential benefit of high-dose vitamin supplementation on immunological and virological end points. However, limited by small samples and short follow-up, these studies remain insufficient to determine whether prolonged high-dose multivitamin supplementation in the context of HAART is safe and can improve clinical outcomes.
  
  We have previously shown that highdose multivitamin supplementation compared with placebo reduced the risk of HIV disease progression and increased CD4 counts among women infected with HIV not receiving HAART.
  To test the hypothesis that high-dose multivitamin supplementation compared with standard-dose supplementation decreases the risk of HIV disease progression or death and improves immunological, virological, and nutritional parameters in patients infected with HIV receiving HAART, we conducted a double-blind, randomized controlled trial of multivitamin supplementation (including vitamin B complex, vitamin C, and vitamin E) in adults initiating ART in Dar es Salaam,
  Tanzania. A single level of the recommended dietary allowance (RDA) was provided as the comparator regimen, rather than placebo, to increase the generalizability of our findings to patients in developed and developing countries where a standard RDA multivitamin supplement may be consumed.

I risultati sono ampiamente segnalati e discussi negli articoli che ho linkato nei miei post precedenti, quindi non li riporto; ma possono essere sintetizzati così:

Di questo studio, non trovo i risultati dei pazienti con placebo, oppure un confronto tra pazienti con una intregrazione media e quelli che non prendono alcun integratore.
Ma sopratutto, sarebbe stato molto interessante se avessero raccolto anche i dati riguardo ad una integrazione medio-bassa.

Praticamente tutti gli studi raccolti in questo thread sembrano indirizzati a dimostrare l'inutilità, o la dannosità, dell'iper-integrazione.

[skydrake]

Scommetto che se uno raddoppia o triplica anche le dosi della propria HAART, finisce conciato abbastanza male.

Lo scommetto pure io Sky
Però, siamo onesti, fosse solo perché una pastiglia di Atripla costa 36€, mi pare difficile cadere in una simile tentazione.

Siamo onesti, buona parte degli studi raccolti in questo thread sembrano indirizzati a dimostrare l'inutilità, o la dannosità, dell'iper-integrazione.

Ma qui, a partire dal titolo, si estende la pericolosità dell'iper-integrazione anche all'integrazione.

Ad esempio, nello studio in Tarzania, qui sopra, il primo gruppo prende 80mg di Vitamina C (quindi il 133% dell'RDA), il secondo 500mg (quindi l'833% dell'RDA). Per forza il secondo non traeva benefici, era tutta roba in più.

Da questo punto di vista, lo studio in Tarzania è totalmente inutile come risvolti pratici nella vita di tutti i giorni (solo Pauling proponeva di assumere parecchi grammi di vitamina C al giorno) ed un suo utilizzo al di fuori dell'iperintegrazione sarebbe fazioso.

Mi chiedo quali risultati ci sarebbero stati se avessero utilizzato lo stesso modus operandi con gli antiretrovirali, ad esempio, col Kaletra (dose prevista per un adulto: 200mg al giorno).
Cosa sarebbe successo se al primo gruppo avessero dato 266 mg di Kaletra (il 133% dell'RDA) e al secondo gruppo 1,66 grammi al giorno (l'866% dell'RDA)?
Ti sareasti aspettato benefici ulteriori nel secondo gruppo?
Io no. Ma se estendersi questa logica, come qui sopra c'è scritto GLI INTEGRATORI? FANNO VENIRE IL CANCRO, allora si potrebbe scrivere GLI ANTIRETROVIRALI? FANNO VENIRE IL CANCRO.

Allora, Uffa, cosa ti saresti aspettato dal secondo gruppo?
Oppure occorrerebbe un ragionamento critico sui dosaggi (preferibilmente dividendole in piu fasce), considerando che le dosi spesso proposte sono dosi da cavallo?

[Dora]

Da aidsmeds.com.

GLI INTEGRATORI CHE POSSONO RALLENTARE L'HIV POSSONO ALIMENTARE IL CANCRO ALLA PROSTATA

February 27, 2014

In alcuni uomini, alte dosi di integrazione con selenio e vitamina E possono aumentare il rischio di cancro aggressivo alla prostata. Questo è particolarmente importante per le persone con HIV, perché uno studio recente ha mostrato che l'integrazione con certe particolari combinazioni di multivitaminici, compresi la vitamina E e il selenio, potrebbe diminuire la progressione della malattia da HIV fra coloro che sono naive ai farmaci e hanno più di 350 CD4.

I ricercatori, che hanno pubblicato i loro risultati nel Journal of the National Cancer Institute, hanno condotto uno studio randomizzato, controllato con placebo su 35.000 uomini, che hanno ricevuto alte dosi di vitamina E (400 IU al giorno), alte dosi di selenio (200 microgrammi al giorno), o entrambi. Impostato per durare 12 anni, lo studio è iniziato nel 2001, ma è stato fermato in anticipo nel 2008, perché era evidente che il selenio non dava nessuna protezione contro il cancro alla prostata e che la vitamina E poteva aumentarne il rischio. Gli uomini sono poi stati seguiti per altri 2 anni.

Fra coloro che hanno iniziato lo studio con un livello di selenio alto e che hanno integrato con alte dosi di questo elemento, il rischio di cancro alla prostata è aumentato del 91%. I loro livelli di selenio sono divenuti tossici.

Gli uomini che hanno iniziato con bassi livelli di selenio e hanno integrato solo con alte dosi di vitamina E hanno avuto un rischio di cancro alla prostata aumentato del 63%, mentre il rischio di cancro aggressivo alla prostata è aumentato del 111%.

Fra i partecipanti che avevano bassi livelli di selenio, prendere selenio oltre alla vitamina E ha costituito una protezione contro gli effetti dannosi della vitamina E.

"Molti pensano che gli integratori siano utili, o alla peggio innocui. Questo non è vero" - ha detto il primo autore dello studio, il professor Alan Kristal, Fred Hutchinson Cancer Research Center. "Da molti altri studi sappiamo che alcuni integratori presi a dosaggi alti - cioè integratori che danno molto di più dell'ammontare quotidiano raccomandato dei micronutrienti - aumentano il rischio di cancro. Lo sapevamo per i folati e per il beta carotene, sulla base di studi randomizzati, controllati e in doppio cieco. Ora lo sappiamo per la vitamina E e per il selenio".

• - Abstract: Baseline Selenium Status and Effects of Selenium and Vitamin E Supplementation on Prostate Cancer Risk
  - Comunicato stampa: Selenium and vitamin E supplements can increase risk of prostate cancer in some men

[skydrake]

Da aidsmeds.com.

GLI INTEGRATORI CHE POSSONO RALLENTARE L'HIV POSSONO ALIMENTARE IL CANCRO ALLA PROSTATA

February 27, 2014

In alcuni uomini, alte dosi di integrazione con selenio e vitamina E possono aumentare il rischio di cancro aggressivo alla prostata.

[..]