Low Sodium but not Low Fructose Improves mtDNA

 

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Dear Editor,

We read with interest the pilot study by Hernández-Rios et al. comparing the effect of a low sodium diet with or without fructose restriction under isocaloric conditions on mitochondrial DNA (mtDNA) and oxidative stress [1]. We are concerned that the reporting of the study may lead to a misrepresentation of the effect of fructose on mtDNA.

The title and last sentence of the introduction suggests that low fructose has an increasing effect on mtDNA. The combination of low sodium and low fructose did increase mtDNA but it did not increase it more than the low sodium diet alone without fructose restriction. This suggests that the effect appears dependent on sodium but not fructose. It is possible that with greater power, they may have detected a significant difference between the 2 groups, as there was a tendency for lower mtDNA in the low sodium diet without fructose restriction, but given the extremely large variance around the means this conclusion remains unsupported.

To show an adverse effect of fructose likely requires an imbalanced, hypercaloric or hypocaloric comparison, in which fructose provides or displaces excess energy in the diet compared with the same diet without any manipulation. Stanhope et al. showed an increasing trend for lipid oxidation when the fructose diet provided an additional 25% of energy compared to the usual diet alone without the excess energy from fructose in 32 overweight/obese individuals (the trial featured an 8 week outpatient ad libitum, overfeeding period followed by a 2-week inpatient energy-balanced, weight-maintaining period) [2], although the same was not found to be true in a similar trial in healthy participants [3]. In line with this finding, our research group through a series of systematic reviews and meta-analyses of controlled feeding trials has shown that supplementing background diets with excess energy from fructose consistently leads to adverse effects on cardiometabolic risk factors associated with inflammation, including body weight [4], fasting and postprandial blood lipids [5] [6], fasting glucose and insulin [7], uric acid [8], and markers of non-alcoholic fatty liver disease (NAFLD) [9]. Conversely, in isocaloric comparisons where energy intake is matched, these effects are not observed. That is, fructose behaves no worse than any other carbohydrate [4] [5] [6] [7] [8], although there may be a dose-threshold for some fasting lipid effects [4] [10] [11] [12]. This lack of effect remains true even under conditions of fructose overfeeding (positive energy balance), as long as the comparison is matched for the excess calories. Taken together, the main driver mediating any harm attributable to fructose appears to be excess energy.

In conclusion, there is insufficient evidence to conclude that fructose restriction has a significant effect on mtDNA and oxidative stress when holding energy equal. Energy imbalance appears to be a prerequisite for eliciting an effect. If the authors wish to build on the present pilot study, then they will need to consider using an imbalanced, hypercaloric or hypocaloric design in which the intervention arm necessarily provides or displaces excess energy.

• References

• 1 Hernandez-Rios R, Hernandez-Estrada S, Cruz-Robles D et al. Low fructose and low salt diets increase mitochondrial DNA in white blood cells of overweight subjects. Exp Clin Endocrinol Diabetes. 2013; 121: 535-538
  Article in Thieme ConnectPubMedGoogle Scholar
• 2 Stanhope KL, Schwarz JM, Keim NL et al. Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans. The Journal of clinical investigation 2009; 119: 1322-1334 DOI: 10.1172/JCI37385.
  CrossrefPubMedGoogle Scholar
• 3 Le KA, Faeh D, Stettler R et al. A 4-wk high-fructose diet alters lipid metabolism without affecting insulin sensitivity or ectopic lipids in healthy humans. The American journal of clinical nutrition 2006; 84: 1374-1379
  PubMedGoogle Scholar
• 4 Sievenpiper JL, de Souza RJ, Mirrahimi A et al. Effect of fructose on body weight in controlled feeding trials: a systematic review and meta-analysis. Annals of internal medicine 2012; 156: 291-304 DOI: 10.7326/0003-4819-156-4-201202210-00007.
  CrossrefPubMedGoogle Scholar
• 5 Sievenpiper JL, Carleton AJ, Chatha S et al. Heterogeneous effects of fructose on blood lipids in individuals with type 2 diabetes: systematic review and meta-analysis of experimental trials in humans. Diabetes care 2009; 32: 1930-1937 DOI: 10.2337/dc09-0619.
  CrossrefPubMedGoogle Scholar
• 6 Wang DDSJ, de Souza RJ et al. Effect of fructose on postprandial triglycerides: A systematic review and meta-analysis of controlled feeding trials. Atherosclerosis 2014; 232: 125-133 doi: 10.1016/j.atherosclerosis.2013.10.019.
  CrossrefPubMedGoogle Scholar
• 7 Cozma AI, Sievenpiper JL, de Souza RJ et al. Effect of fructose on glycemic control in diabetes: a systematic review and meta-analysis of controlled feeding trials. Diabetes care 2012; 35: 1611-1620 DOI: 10.2337/dc12-0073.
  CrossrefPubMedGoogle Scholar
• 8 Wang DD, Sievenpiper JL, de Souza RJ et al. The effects of fructose intake on serum uric acid vary among controlled dietary trials. The Journal of nutrition 2012; 142: 916-923 DOI: 10.3945/jn.111.151951.
  CrossrefPubMedGoogle Scholar
• 9 Chiu S, Sievenpiper JL, de Souza RJ et al. Effect of fructose on markers of non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of controlled feeding trials. Eur J Clin Nutr 2014; 68: 416-423 doi: 10.1038/ejcn.2014.8
  CrossrefPubMedGoogle Scholar
• 10 Livesey G, Taylor R. Fructose consumption and consequences for glycation, plasma triacylglycerol, and body weight: meta-analyses and meta-regression models of intervention studies. Am J Clin Nutr 2008; 88: 1419-1437
  PubMedGoogle Scholar
• 11 Zhang YH, An T, Zhang RC et al. Very high fructose intake increases serum LDL-cholesterol and total cholesterol: a meta-analysis of controlled feeding trials. The Journal of nutrition 2013; 143: 1391-1398 DOI: 10.3945/jn.113.175323.
  CrossrefPubMedGoogle Scholar
• 12 Chiavaroli L, Mirrahimi A, de Souza RJ et al. Meta-Analysis of Fructose and Cholesterol: A Concern regarding Missing Data. J Nutr 2014; DOI: 110.3945/jn.113.187757.
  PubMedGoogle Scholar