[Imagem: grandmedica.by]
Volta e meia surge algum artigo, com grande promoção midiática, incriminando algum alimento ou alguma molécula que é parte integrante da nossa fisiologia, que tem função protetora, anti-inflamatória: o caso do colesterol já é clássico nesse sentido.
Mas e a frutose, quem esperaria uma ofensiva contra ela – validada por setores da medicina – e, no limite, criminalizando as frutasɁ
Há pouco mais de dez anos um endocrinologista encontrou abertas todas as portas da mídia e todo o eco que precisava na medicina para fustigar a frutose e convertê-la em uma droga.
Segundo seu estudo, o açúcar da fruta era um veneno do quilate do álcool e um tóxico hepático idem.
A frutose seria – segundo aquele pesquisador, um veneno que produziria esteatose hepática [“fígado gordo”], obesidade, resistência insulínica [pré-diabetes] e também obesidade.
A lenda não mais se deteve. Talvez porque interessasse a algum grupo - não é nosso tema aqui -, no entanto faz sentido examiná-la até para mostrar, nesse caso, mais um exemplo de como certas ideias surreais atravessam a medicina e são repetidas até o infinito pela corporação dos médicos. Sem que se ofereça, suficientemente e no espaço adequado, o debate do contraditório.
O cientista acima mencionado, o Dr Robert Lusting [J], produziu um discurso, que viralizou nas redes sociais, intitulado “A amarga verdade sobre o açúcar”. Sua ideia-mestra: frutose engorda, frutose enche o fígado de gordura, dá diabetes.
E aqui não importou quanta evidência ele tinha – em termos de estudos humanos ou em bioquímica – o fato é que a lenda ganhou corpo. Ganhou status de verdade científica, somando-se – com total acolhida – à lenda do açúcar-veneno que, como regra, transcende a frutose.
Mas neste caso da frutose, o truque teórico foi o de tomar uma pequena verdade bioquímica, fisiológica, e lhe atribuir uma dimensão e um poder que ela absolutamente não tinha. Nem tem. Não em nós, humanos.
Aquele endócrino-pediatra fez o estudo em ratos e extrapolou. Forçou seus ratos a consumir uma dose surreal de frutose [mais de 60% do total das calorias diárias da sua alimentação] e, sim, conseguiu engordar ratos e fazer com que apresentassem fígados gordos. Dispunha de um fato que ele tratou de interpretar do seu jeito.
Primeiro problema no caminho da sua interpretação: os ratos.
Ratos possuem capacidade bioquímica [genética de rato] indiscutível e bem importante de converter frutose em gordura. É um processo que ocorre no fígado deles e, sim, também no nosso, só que no caso dos humanos é residual [I]. Em nós não passa de 2%, enquanto em ratos, chega a 60%, principalmente quando forçados a consumir uma dose para nada realista de frutose [o correspondente a mais de 5 litros de refrigerante em nós].
Nos humanos, a via mais natural, a preferida, da frutose é ser queimada e muito mais rapidamente que qualquer açúcar, além de armazenada como açúcar de reserva [glicogênio]. Ela sequer necessita da insulina para entrar na célula. É um açúcar insuline-like. Possui o mais baixo índice glicêmico. Portanto não dá pico insulínico. E sem este não há facilidade para acumular gordura. A frutose não aumenta resistência insulínica, portanto; ao contrário. É o açúcar ideal para diabéticos, segundo R. Peat.
“Os carboidratos são distribuídos de três diferentes maneiras: eles podem ser combinados com oxigênio para produzir energia, armazenados como glicogênio nos músculos e no fígado, ou convertidos em ácidos graxos através da via de novo lipogênese e então armazenados como triglicérides.
Um argumento comum contra a frutose, portanto, é o de que ela é enviada diretamente para o fígado onde é convertida em gordura, desencadeando o estado de doença gordurosa do fígado, diabetes e obesidade.
Enquanto que é verdade que o fígado rapidamente usa frutose, ele o faz primariamente para recompor o estoque de glicogênio. Em determinado estudo, uma infusão de frutose resultou em 360% mais glicogênio do que infusão de outro açúcar, a glicose; e a capacidade do fígado para armazenar glicogênio é muito grande.
Outro estudo sugeriu que ´lipogênese de novo não é uma importante via bioquímica em humanos´ e que grande oferta de cerca de 500 g seria necessária antes que a via da lipogênese de novo se tornasse significante. O fígado usa glicogênio localmente para suas variadas tarefas, portanto manter o fígado energizado é uma maneira simples efetiva de amparar a sua função”[C].
Provavelmente o Dr Lusting foi instrumento de alguma causa, por assim dizer. E confundiu muita gente por muito tempo. Conscientemente ou não, praticou mais ideologia do que medicina.
Mas, no real, ele somente provou que frutose, em ratos, possui efeitos negativos para a saúde [nas doses irreais que ele usou] dos ratos, nada mais que isso.
A experiência já demonstrou, em humanos, o contrário do que ele imaginou: frutose é terapêutica para detoxificar fígado gordo, e muito rapidamente. Frutose aumenta a produção de energia e de CO2. E assim por diante. Aumenta retenção de minerais alcalinos como magnésio. Frutose promove a termogênese. A frutose é fundamental para a nossa saúde, em qualquer perspectiva.
Pode ser que aquele doutor fez um bom estudo para ratos, seguramente um estudo midiático, de grande e duradoura repercussão na medicina dominante, mas quando examinado de perto, revela uma mistura indevida entre ratos e humanos. E um desserviço ao açúcar das frutas. Para a glória do mito açucarfóbico.
GM Fontes, Brasília, 31-7-23
As informações aqui presentes não pretendem servir para uso diagnóstico, prescrição médica, tratamento, prevenção ou mitigação de qualquer doença humana. Não pretendem substituir a consulta ao profissional médico ou servir como recomendação para qualquer plano de tratamento. Trata-se de informações com fins estritamente educativos.
Referências ___________________
[A] TAPPY, L, JÉQUIER E, 1993. Fructose and dietary thermogenesis. Am J Clin Nutr. 1993 Nov;58(5 Suppl):766S-770S. doi: 10.1093/ajcn/58.5.766S. PMID: 8213608 DOI: 10.1093/ajcn/58.5.766S “Ingestion of nutrients increases energy expenditure above basal metabolic rate. Thermogenesis of carbohydrate comprises two distinct components: an obligatory component, which corresponds to the energy cost of carbohydrate absorption, processing, and storage; and a facultative component, which appears to be related with a carbohydrate-induced stimulation of the sympathetic nervous system, and can be inhibited by beta-adrenergic antagonists. Fructose ingestion induces a greater thermogenesis than does glucose. This can be explained by the hydrolysis of 3.5-4.5 mol ATP/mol fructose stored as glycogen, vs 2.5 mol ATP/mol glucose stored. Therefore the large thermogenesis of fructose corresponds essentially to an increase in obligatory thermogenesis. Obese individuals and obese patients with non-insulin-dependent diabetes mellitus commonly have a decrease in glucose-induced thermogenesis. These individuals in contrast display a normal thermogenesis after ingestion of fructose. This may be explained by the fact that the initial hepatic fructose metabolism is independent of insulin. This observation indicates that insulin resistance is likely to play an important role in the decreased glucose-induced thermogenesis of these individuals”. A frutose não depende da insulina e frutose aumenta termogênese.
[B] TAPPY, L, RANDIN J P, 1986. Comparison of thermogenic effect of fructose and glucose in normal humans. Am J Physiol . 1986 Jun;250(6 Pt 1):E718-24. doi: 10.1152/ajpendo.1986.250.6.E718. PMID: 3521319. DOI: 10.1152/ajpendo.1986.250.6.E718 “After nutrient ingestion there is an increase in energy expenditure that has been referred to as dietary-induced thermogenesis. In the present study we have employed indirect calorimetry to compare the increment in energy expenditure after the ingestion of 75 g of glucose or fructose in 17 healthy volunteers. During the 4 h after glucose ingestion the plasma insulin concentration increased by 33 +/- 4 microU/ml and this was associated with a significant increase in carbohydrate oxidation and decrement in lipid oxidation. Energy expenditure increased by 0.08 +/- 0.01 kcal/min. When fructose was ingested, the plasma insulin concentration increased by only 8 +/- 2 microU/ml vs. glucose. Nonetheless, the increments in carbohydrate oxidation and decrement in lipid oxidation were significantly greater than with glucose. The increment in energy expenditure was also greater with fructose. When the mean increment in plasma insulin concentration after fructose was reproduced using the insulin clamp technique, the increase in carbohydrate oxidation and decrement in lipid oxidation were markedly reduced compared with the fructose-ingestion study; energy expenditure failed to increase above basal levels. To examine the role of the adrenergic nervous system in fructose-induced thermogenesis, fructose ingestion was also performed during beta-adrenergic blockade with propranolol. The increase in energy expenditure during fructose plus propranolol was lower than with fructose ingestion alone. These results indicate that the stimulation of thermogenesis after carbohydrate ingestion is related to an augmentation of cellular metabolism and is not dependent on an increase in the plasma insulin concentration per se.(ABSTRACT TRUNCATED AT 250 WORDS)” Comparada com a glicose, a frutose aumenta muito pouco a insulina. E frutose aumenta a termogênese.
[C] RODDY, Danny. The centrality of the liver in pattern baldness, 16/7/2015. Aqui a palavra carboidrato está mal empregada, já que ela inclui carboidratos não digeríveis e não é o caso dessa classificação. Melhor teria sido falar em açúcares.
[D] ANUNDI I, KING J, OWEN D A, 1987. Fructose prevents hypoxic cell death in liver. Am J Physiol. 1987 Sep;253(3 Pt 1):G390-6. doi: 10.1152/ajpgi.1987.253.3.G390. PMID: 3631273 DOI: 10.1152/ajpgi.1987.253.3.G390 “Perfusion of livers from fasted rats with nitrogen-saturated buffer caused hepatocellular damage within 30 min. Lactate dehydrogenase (LDH) was released at maximal rates of approximately 300 U . g-1 . h-1 under these conditions, and virtually all cells in periportal and pericentral regions of the liver lobule were stained with trypan blue. Infusion of glucose, xylitol, sorbitol, or mannitol (20 mM) did not appreciably change the time course or extent of damage due to perfusion with nitrogen-saturated perfusate. However, fructose (20 mM) completely prevented damage assessed by LDH release, trypan blue uptake, and ultrastructural changes for at least 2 h of perfusion. Neither glucose, xylitol, sorbitol, nor mannitol (20 mM) increased lactate formation above basal levels during hypoxia. On the other hand, fructose (0.4-20 mM) caused a concentration-dependent increase in lactate formation that reached maximal rates of approximately 180 mumol . g-1 . h-1. The dose-dependent increase in glycolytic lactate production from fructose correlated well with cellular protection reflected by decreases in LDH release. ATP:ADP ratios were also increased from 0.4 to 1.8 in a dose-dependent manner by fructose. The results indicate that fructose protects the liver against hypoxic cell death by the glycolytic production of ATP in the absence of oxygen”.
[E] MASCORD, D, SMITH J, 1991. The effect of fructose on alcohol metabolism and on the [lactate]/[pyruvate] ratio in man. Alcohol Alcohol. 1991;26(1):53-9. PMID: 1854373 “Ten male subjects were given alcohol by intravenous infusion and maintained at a constant blood alcohol level. The rate of alcohol metabolism was measured before and after an oral dose of fructose (100 g), as the amount of alcohol required to maintain the steady state. The mean rate of alcohol metabolism increased by 80% after fructose but there was considerable variation among the subjects, which was related to their plasma fructose concentrations. Blood lactate increased after fructose to a greater degree than blood pyruvate, resulting in a significant increase in [lactate]/[pyruvate] ratio. Since fructose increased the [lactate]/[pyruvate] ratio when it increased alcohol metabolism, the action of fructose cannot be explained by a decrease in the liver cytoplasmic [NADH]/[NAD] ratio and some other mechanism must be sought”.
[F] TAPPY,L, KIM-ANNE, L, 2012. Does fructose consumption contribute to non-alcoholic fatty liver disease? Clin Res Hepatol Gastroenterol. 2012 Dec;36(6):554-60. doi: 10.1016/j.clinre.2012.06.005. Epub 2012 Jul 12. PMID: 22795319. DOI: 10.1016/j.clinre.2012.06.005 “Fructose is mainly consumed with added sugars (sucrose and high fructose corn syrup), and represents up to 10% of total energy intake in the US and in several European countries. This hexose is essentially metabolized in splanchnic tissues, where it is converted into glucose, glycogen, lactate, and, to a minor extent, fatty acids. In animal models, high fructose diets cause the development of obesity, insulin resistance, diabetes mellitus, and dyslipidemia. Ectopic lipid deposition in the liver is an early occurrence upon fructose exposure, and is tightly linked to hepatic insulin resistance. In humans, there is strong evidence, based on several intervention trials, that fructose overfeeding increases fasting and postprandial plasma triglyceride concentrations, which are related to stimulation of hepatic de novo lipogenesis and VLDL-TG secretion, together with decreased VLDL-TG clearance. However, in contrast to animal models, fructose intakes as high as 200 g/day in humans only modestly decreases hepatic insulin sensitivity, and has no effect on no whole body (muscle) insulin sensitivity. A possible explanation may be that insulin resistance and dysglycemia develop mostly in presence of sustained fructose exposures associated with changes in body composition. Such effects are observed with high daily fructose intakes, and there is no solid evidence that fructose, when consumed in moderate amounts, has deleterious effects. There is only limited information regarding the effects of fructose on intrahepatic lipid concentrations. In animal models, high fructose diets clearly stimulate hepatic de novo lipogenesis and cause hepatic steatosis. In addition, some observations suggest that fructose may trigger hepatic inflammation and stimulate the development of hepatic fibrosis. This raises the possibility that fructose may promote the progression of non-alcoholic fatty liver disease to its more severe forms, i.e. non-alcoholic steatohepatitis and cirrhosis. In humans, a short-term fructose overfeeding stimulates de novo lipogenesis and significantly increases intrahepatic fat concentration, without however reaching the proportion encountered in non-alcoholic fatty liver diseases. Whether consumption of lower amounts of fructose over prolonged periods may contribute to the pathogenesis of NAFLD has not been convincingly documented in epidemiological studies and remains to be further assessed”.
[G] DOLAN, L C, POTTER, S M, 2010. Evidence-based review on the effect of normal dietary consumption of fructose on development of hyperlipidemia and obesity in healthy, normal weight individuals. Crit Rev Food Sci Nutr. 2010 Jan;50(1):53-84. doi: 10.1080/10408390903461426. PMID: 20047139 DOI: 10.1080/10408390903461426 “In recent years, there has been episodic speculation that an increase in consumption of fructose from foods and beverages is an underlying factor responsible for the relatively recent increase in obesity and obesity-related diseases such as diabetes. Reports in support of this hypothesis have been published, showing that concentrations of triglycerides (TG) are higher and concentrations of insulin and hormones associated with satiety are lower in animals following the ingestion of fairly large quantities of fructose, compared to other carbohydrates. However, results from human studies are inconsistent. A possible reason for the inconsistent results is that they are dependent on the particular study population, the design of the studies, and/or the amount of fructose administered. A systematic assessment of the strength and quality of the studies and their relevance for healthy, normal weight humans ingesting fructose in a normal dietary manner has not been performed. The purpose of this review was to critically evaluate the existing database for a causal relationship between the ingestion of fructose in a normal, dietary manner and the development of hyperlipidemia or increased body weight in healthy, normal weight humans, using an evidence-based approach. The results of the analysis indicate that fructose does not cause biologically relevant changes in TG or body weight when consumed at levels approaching 95th percentile estimates of intake”.
[H] RIZKALLA, S W, 2010. Health implications of fructose consumption: A review of recent data. Nutr Metab (Lond). 2010 Nov 4;7:82. doi: 10.1186/1743-7075-7-82. PMID: 21050460 PMCID: PMC2991323 DOI: 10.1186/1743-7075-7-82 “This paper reviews evidence in the context of current research linking dietary fructose to health risk markers.Fructose intake has recently received considerable media attention, most of which has been negative. The assertion has been that dietary fructose is less satiating and more lipogenic than other sugars. However, no fully relevant data have been presented to account for a direct link between dietary fructose intake and health risk markers such as obesity, triglyceride accumulation and insulin resistance in humans. First: a re-evaluation of published epidemiological studies concerning the consumption of dietary fructose or mainly high fructose corn syrup shows that most of such studies have been cross-sectional or based on passive inaccurate surveillance, especially in children and adolescents, and thus have not established direct causal links. Second: research evidence of the short or acute term satiating power or increasing food intake after fructose consumption as compared to that resulting from normal patterns of sugar consumption, such as sucrose, remains inconclusive. Third: the results of longer-term intervention studies depend mainly on the type of sugar used for comparison. Typically aspartame, glucose, or sucrose is used and no negative effects are found when sucrose is used as a control group.Negative conclusions have been drawn from studies in rodents or in humans attempting to elucidate the mechanisms and biological pathways underlying fructose consumption by using unrealistically high fructose amounts.The issue of dietary fructose and health is linked to the quantity consumed, which is the same issue for any macro- or micro nutrients. It has been considered that moderate fructose consumption of ≤50g/day or ~10% of energy has no deleterious effect on lipid and glucose control and of ≤100g/day does not influence body weight. No fully relevant data account for a direct link between moderate dietary fructose intake and health risk markers”.
[I] SIEVENPIPER, J, Dr, 2012. Fate of fructose: Interview with Dr. John Sievenpiper. 26 May 2012. John Sievenpiper, M.D., of St. Michael's Hospital, University of Toronto, brings a valuable perspective to our understanding of sugar. He is the lead author of three recent systematic reviews and meta-analyses evaluating fructose's effects on body weight, blood pressure, and glycemic control in humans from randomized controlled feeding trials.
With only very light edits made (for clarity) to my transcribed interview with him by telephone, I give you the take of Dr. Sievenpiper on fructose in his own words:
[excertos]
“JS: The confusion really lies in that a lot of this debate has been underpinned by the animal literature and ecological studies without recognizing the flaws and translating that information into real-world human scenarios. The problem has really been with someone like Lustig who can run through the pathways at very impressive clip and can convince someone that, OK, there's so much biological plausibility, so it must be true."
“We decided to use the gold standard or highest level of evidence in nutrition or, really, in most fields -- which is controlled trials; and, in nutrition, is controlled dietary feeding trials. We wanted to apply the best tools we have, which was systematic review and meta-analyses tools to synthesize that knowledge and information to try to answer the question.
Is it true? What we found was that it wasn't. We looked at bodyweight -- which is the Annals [of Internal Medicine] data that you're aware of -- in each case there was no effect of fructose when it was isocalorically exchanged. There was no adverse effect on bodyweight, blood pressure, or uric acid. We do see a very consistent and strong effect on bodyweight when fructose is providing excess energy”.
“ The fructose is providing excess energy. Is it the fructose you're adding? Is it the energy from fructose? Those are actually difficult to interpret. What we found is that the energy is dominant when you look at neutral, positive, or negative energy balance studies. We found that as long as fructose was isocalorically exchanged, there was no effect. Fructose wasn't having an effect beyond energy. Our conclusions looking were that energy appears to be dominant in particular case to bodyweight. The bodyweight increase we saw was predicted by the energy was consumed. We would say the same thing, although we didn’t have as many studies, for uric acid. In our lipid analyses, we find the same thing again. Energy is dominant”.
“There is really the disconnect between animal carbohydrate metabolism and human carbohydrate (or fructose) metabolisms. One of my criticisms of using animal data is that they feed at superphysiological levels at 60 percent energy. No one is consuming that.
The 50th percentile for intake in the United States is 49g per day, which is just a little less than 10 percent per day of energy from fructose. We're talking of a six-fold difference in what people are really consuming and what these models are feeding. If you look at even the 95th percentile for intake of fructose in US population from using NHANES data, the 95 percentile for intake for NHANES for fructose consumes 87g of sugar or little less than 20 percent energy. (NHANEs is intake data as opposed to disappearance data, what the USDA collects, which is just availability of sugars, but tends to overestimate because it doesn't account for waste; it looks at how much went onto the market; when you only fill your coffee half full with that sachet of sugar and throw away the rest, it doesn't count for how much was thrown away). So these models are feeding even three-fold, if we're generous, compared to the 95th percentile of the population are consuming, which is really super-physiologic. Just based on the feeding pattern and paradigm of those models, you can't equate them.
On top of that, we know that if you look at comparative physiological studies, animals metabolize carbohydrates differently than do humans. In animals on a high-carbohydrate diet not providing excess energy, you find that de novo lipogenesis [conversion by the liver to fatty acids] is anywhere from 50 percent or higher. They basically make fatty acids for at least 50 percent of the carbohydrate [consumed]. De novo lipogenesis accounts for at least 50 percent carbohydrate. In humans, it is very, very hard under isocaloric (neutral energy) conditions, let alone in overfeeding conditions, to push that beyond 10 percent or even 20 percent.
A lot of the outcomes that have been implicated, have really centered on this hypothesis of de novo lipogenesis. I have a really big problem when people want to extrapolate from an animal study where their feeding (1) superphysiological amounts of fructose and (2) in a model where the metabolism is not the same as in humans – it's very different. It's bad for rats or mice (you name your study and adverse effect of fructose), but it doesn't mean that's the case in humans. Again, that's the reason why I think we need good human data and that's why we wanted to synthesize the human data. We do have almost 50 controlled feeding studies on different questions related to cardiometabolic control”.
“ If you actually look at the animal studies where you feed them high fructose, you make this beautiful metabolic syndrome phenotype (where they have very high TGs, low HDL, hypertension, obesity, and insulin resistance). We don't see that in humans. It doesn't hold true because when you actually look at carefully conducted studies.
Dr. Rippe was actually quoting Luc Tappy's work. He has put together a really excellent review of his own work and that of others who've done careful stable isotope tracer studies where you can label acetate, fructose, and different metabolites. You can see where fructose is going and where fructose is ending up. What he's found is that with a fructose load 50 percent goes to glucose, about 25 percent goes to lactate, greater than 15 percent and up goes to glycogen, the remainder would be oxidized directly [going to CO2 through the TCA cycle], and a small portion contributed to de novo lipogenesis. I can't remember what Dr. Rippe had on his diagram, but even as low as, let's say, 3 percent, it is really quantitatively non-significant. In animals, de novo lipogenesis is quantitatively significant. It doesn't appear in humans with high-carbohydrate feeding and the same is true even under high-fructose feeding. We see this very robust de novo lipogenesis in animals. We don't see it in humans”.
“With all the nuances, we’ve done a pretty bad job at communicating it as opposed to the simple message of "Fructose at any level is poison." We're trying to say it depends on the dose, it depends on the energy, and that’s a hard message to communicate. We've been dwelling on harm. We’ve been saying "Well, it doesn’t support harm except where there is excess energy."
“That's the danger -- that people will say that fruit is a source of fructose and I won't consume fruit because it may induce obesity, metabolic syndrome, and so on. It's not just the lay public that may take this message to heart but professionals. We had an endocrinologist here at our hospital at University of Toronto who was telling patients not to consume fruit because of the fructose content precisely because of all the commentaries, editorials, and reviews that Rob Lustig had been publishing. The danger is that people will take the message to extreme. They'll start saying "I should cut these things out (apples, pears) to cut my fructose exposure." That is a really wrong-headed approach. When I talk to Dr. Lustig on the side, I do get a sense that he does think that there's a dose threshold, but it doesn't come out in the writing, or the YouTube piece”.
Note: When I reached out to Dr. Sievenpiper, he was gracious enough to point me to a just-published "lovely, balanced, well-written paper" by respected physiologist Luc Tappy of Université de Lausanne, in Switzerland. The paper, Dr. Sievenpiper said, summarized much of Dr. Tappy's own take after the event in San Diego and would help answer more questions. (The open-access paper can be found here.)
http://evolvinghealthscience.blogspot.com/2012/05/fate-of-fructose-interview-with-dr-john.html
[J] O Dr Lusting era um pediatra-endocrinologista norte-americano. Ele culpou o veneno frutose pela epidemia de obesidade nos USA. Antes dele, houvera J Yudkin, britânico, em 1972 rotulando o açúcar comum como droga viciante branca e letal. São décadas em que açúcar e gordura saturada povoam o imaginário de setores da medicina como grandes vilões da doença cardiovascular e da obesidade. Sendo que a repressão ao consumo dos dois não nos trouxe povos menos obesos nem fez decair qualitativamente a doença cardiovascular ou a obesidade. Ver, a respeito, LESLIE, Ian, 2016. The sugar conspiracy.
https://www.theguardian.com/society/2016/apr/07/the-sugar-conspiracy-robert-lustig-john-yudkin
[L] Peat, R. Sugar myths. Os textos do pesquisador independente Ray Peat, são o que de melhor pode ser encontrado na literatura científica a respeito do açúcar e a saúde humana.
***