Long-term Nutritional Supplementation Research Articles

Effects of long-term intradialytic oral nutrition and exercise on muscle protein homeostasis and markers of mitochondrial content in patients on hemodialysis.

Patients with end-stage kidney disease on maintenance hemodialysis commonly develop protein-energy wasting, a syndrome characterized by nutritional and metabolic abnormalities. Nutritional supplementation and exercise are recommended to prevent protein-energy wasting. In a 6-mo prospective randomized, open-label, clinical trial, we reported that the combination of resistance exercise and nutritional supplementation does not have an additive effect on lean body mass measured by dual-energy X-ray absorptiometry. To provide more mechanistic data, we performed a secondary analysis where we hypothesized that the combination of nutritional supplementation and resistance exercise would have additive effects on muscle protein accretion by stable isotope protein kinetic experiments, muscle mass by MRI, and mitochondrial content markers in muscle. We found that 6 mo of nutritional supplementation during hemodialysis increased muscle protein net balance [baseline: 2.5 (-17.8, 13.0) µg·100 mL-1·min-1 vs. 6 mo: 43.7 (13.0, 98.5) µg·100 mL-1·min-1, median (interquartile range), P = 0.04] and mid-thigh fat area [baseline: 162.3 (104.7, 226.6) cm2 vs. 6 mo: 181.9 (126.3, 279.2) cm2, median (interquartile range), P = 0.04]. Three months of nutritional supplementation also increased markers of mitochondrial content in muscle. Although the study is underpowered to detected differences, the combination of nutritional supplementation and exercise failed to show further benefit in protein accretion or muscle cross-sectional area. We conclude that long-term nutritional supplementation increases the skeletal muscle anabolic effect, the fat cross-sectional area of the thigh, and markers of mitochondrial content in skeletal muscle.

Association Between Lifestyle Factors, Vitamin and Garlic Supplementation, and Gastric Cancer Outcomes

The associations of lifestyle factors with gastric cancer (GC) are still underexplored in populations in China. Long-term nutritional supplementation may prevent GC in high-risk populations, but the possible effect modification by lifestyle factors remains unknown. To evaluate how lifestyle factors, including smoking, alcohol intake, and diet, may change the risk of GC incidence and mortality and whether the effects of vitamin and garlic supplementation on GC are associated with major lifestyle factors. This is a secondary analysis of the Shandong Intervention Trial, a masked, randomized, placebo-controlled trial that aimed to assess the effect of vitamin and garlic supplementations and Helicobacter pylori treatment on GC in a factorial design with 22.3 years of follow-up. The study took place in Linqu County, Shandong province, China, a high-risk area for GC. Data were collected from Jully 1995 to December 2017. Overall, 3365 participants aged 35 to 64 years identified in 13 randomly selected villages who agreed to undergo gastroscopy were invited to participate in the trial and were included in the analysis. Data analysis was conducted from March to May 2019. Participants received vitamin and garlic supplementation for 7.3 years, H pylori treatment for 2 weeks (among participants with H pylori ), or placebo. The primary outcomes were GC incidence and GC mortality (1995-2017). We also examined the progression of gastric lesions (1995-2003) as a secondary outcome. Of the 3365 participants (mean [SD] age, 47.1 [9.2] years; 1639 [48.7%] women), 1677 (49.8%) were randomized to receive active vitamin supplementation, with 1688 (50.2%) receiving placebo, and 1678 (49.9%) receiving active garlic supplementation, with 1687 (50.1%) receiving placebo. Overall, 151 GC cases (4.5%) and 94 GC deaths (2.8%) were identified. Smoking was associated with increased risk of GC incidence (odds ratio, 1.72; 95% CI, 1.003-2.93) and mortality (hazard ratio [HR], 2.01; 95% CI, 1.01-3.98). Smoking was not associated with changes to the effects of vitamin or garlic supplementation. The protective effect on GC mortality associated with garlic supplementation was observed only among those not drinking alcohol (never drank alcohol: HR, 0.33; 95% CI, 0.15-0.75; ever drank alcohol: HR, 0.92; 95% CI, 0.55-1.54; P for interaction = .03), and significant interactions were only seen among participants with H pylori (never drank alcohol: HR, 0.31; 95% CI, 0.12-0.78; ever drank alcohol: HR, 0.91; 95% CI, 0.52-1.60; P for interaction = .04). No significant interactions between vitamin supplementation and lifestyle factors were found. In this secondary analysis of a randomized clinical trial, smoking was associated with an increased risk of GC incidence and mortality. Not drinking alcohol was associated with a stronger beneficial effect of garlic supplementation on GC prevention. Our findings provide new insights into lifestyle intervention for GC prevention, suggesting that mass GC prevention strategies may need to be tailored to specific population subgroups to maximize the potential beneficial effect. ClinicalTrials.gov Identifier: NCT00339768.

The Bluegreen Algae (AFA) Consumption over 48 Hours Increases the Total Number of Peripheral CD34+ Cells in Healthy Patients: Effect of Short-Term and Long-Term Nutritional Supplementation (Curcumin/AFA) on CD34+ Levels (Blood).

Several active principles from plants could trigger the release of stem cells from the bone marrow. Stem cell mobilizers have shown side effects in patients. Thus, the purpose of this paper is to find the natural products from plants (curcuminoids, glycosinolate of sulforaphane, AFA bluegreen algae), which could be potential stem mobilizes without adverse side effects. The antioxidant curcumin [1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-2,5-dione], glycosinolate of sulforaphane (broccoli) or AFA (Aphanizomenon flos) extract promote beneficial effects in patients. The number of circulating stem cells were monitored by HSC marker-CD34 by flow cytometry in peripheral blood from healthy subjects. CD34 is a hematological stem cells (HSC) marker. A double-blind study was conducted in 22 healthy subjects. We have evaluated whether short-term AFA—Aphanizomenon flos aquae—algae or curcuminoids consumption (powder or liquid formulation) over 48 consecutive hours could increase the total number of peripheral CD34+ blood cells (n = 22, n = 5 subjects/group). The total number of circulating CD34+ cells were quantified after short-term and long-term nutritional supplementation; their levels were compared with their own basal levels (n = 5/group, controls: before taking any supplement) or placebo-treated patients (n = 7); their average age was 54 years old. We also evaluated whether long-term nutritional supplementation with several nutraceuticals could enhance HSC mobilization by increasing the total number of peripheral CD-34+ cell after seven or 38 consecutive days of administration (n = 5, with seven placebo-treated patients). The long-term administration take place with these doses/day [curcuminoids: 2000 mg/day, equivalent to 120 mg of curcuminoids/day), glycosinolate of sulforaphane (66 mg/day), plus AFA Algae bluegreen extract (400 mg/day)]. On the last day (10 a.m.) of treatment, blood samples were collected six hours after taking these supplements; the average age was 54 years old. Notably, the blue green AFA algae extract consumption over 48 h enhances HSC mobilization by increasing the total number of peripheral CD34+ cells. The long-term administration with curcuminoids, glycosinolate of sulforaphane, and AFA bluegreen algae extract also increased the total number of CD34-HSC cells after seven or 38 days of consecutive of administration in healthy subjects.

The Long-Term Algae Extract (Chlorella and Fucus sp) and Aminosulphurate Supplementation Modulate SOD-1 Activity and Decrease Heavy Metals (Hg++, Sn) Levels in Patients with Long-Term Dental Titanium Implants and Amalgam Fillings Restorations.

The toxicity of heavy metals such as Hg++ is a serious risk for human health. We evaluated whether 90 days of nutritional supplementation (d90, n = 16) with Chlorella vulgaris (CV) and Fucus sp extracts in conjunction with aminosulphurate (nutraceuticals) supplementation could detox heavy metal levels in patients with long-term titanium dental implants (average: three, average: 12 years in mouth) and/or amalgam fillings (average: four, average: 15 years) compared to baseline levels (d0: before any supplementation, n = 16) and untreated controls (without dental materials) of similar age (control, n = 21). In this study, we compared levels of several heavy metals/oligoelements in these patients after 90 days (n = 16) of nutritional supplementation with CV and aminozuphrates extract with their own baseline levels (d0, n = 16) and untreated controls (n = 21); 16 patients averaging 44 age years old with long-term dental amalgams and titanium implants for at least 10 years (average: 12 years) were recruited, as well as 21 non-supplemented controls (without dental materials) of similar age. The following heavy metals were quantified in hair samples as index of chronic heavy metal exposure before and after 90 days supplementation using inductively coupled plasma-mass spectrometry (ICP-MS) and expressed as μg/g of hair (Al, Hg++, Ba, Ag, Sb, As, Be, Bi, Cd, Pb, Pt, Tl, Th, U, Ni, Sn, and Ti). We also measured several oligoelements (Ca++, Mg++, Na+, K+, Cu++, Zn++, Mn++, Cr, V, Mo, B, I, P, Se, Sr, P, Co, Fe++, Ge, Rb, and Zr). The algae and nutraceutical supplementation during 90 consecutive days decreased Hg++, Ag, Sn, and Pb at 90 days as compared to baseline levels. The mercury levels at 90 days decreased as compared with the untreated controls. The supplementation contributed to reducing heavy metal levels. There were increased lithium (Li) and germanium (Ge) levels after supplementation in patients with long-term dental titanium implants and amalgams. They also (d90) increased manganesum (Mn++), phosphorum (P), and iron (Fe++) levels as compared with their own basal levels (d0) and the untreated controls. Finally, decreased SuperOxide Dismutase-1 (SOD-1) activity (saliva) was observed after 90 days of supplementation as compared with basal levels (before any supplementation, d0), suggesting antioxidant effects. Conversely, we detected increased SOD-1 activity after 90 days as compared with untreated controls. This SOD-1 regulation could induce antioxidant effects in these patients. The long-term treatment with algae extract and aminosulphurates for 90 consecutive days decreased certain heavy metal levels (Hg++, Ag, Sn, Pb, and U) as compared with basal levels. However, Hg++ and Sn reductions were observed after 90 days as compared with untreated controls (without dental materials). The dental amalgam restoration using activated nasal filters in conjunction with long-term nutritional supplementation enhanced heavy metals removal. Finally, the long-term supplementation with these algae and aminoazuphrates was safe and non-toxic in patients. These supplements prevented certain deficits in oligoelements without affecting their Na+/K+ ratios after long-term nutraceutical supplementation.

Effect of 2-year nutritional supplementation on progression of age-related macular degeneration.

To examine the effect of a long-term nutritional supplementation on age-related macular degeneration progression. In this prospective, double-blind, placebo-controlled study, 80 patients with intermediate age-related macular degeneration were randomized (2:1) to receive 1 tablet/day of a nutritional supplement containing a mixture of carotenoids, vitamins and omega-3 fatty acids or placebo. Age-related macular degeneration progression assessed by digital fundus photography (primary outcome) and best-corrected visual acuity were evaluated. Differences between arms were tested using chi-square test or Fisher's exact test. Seventy-four patients completed the follow-up at 24 months (48 in the treated arm and 26 in the placebo arm). An age-related macular degeneration progression was observed in the 2.1% of patients of the treated arm and in the 15.4% of patients in the placebo arm (p = 0.05, Fisher's exact test). Best-corrected visual acuity data alone were not statistically significant among groups. A clinically meaningful stabilization of intermediate age-related macular degeneration over a period of 2 years may be obtained by treating patients with a mixture of carotenoids, vitamins and omega-3 fatty acids.

Nutritional Supplementation With Physical Activity Improves Muscle Composition in Mobility-Limited Older Adults, The VIVE2 Study: A Randomized, Double-Blind, Placebo-Controlled Trial.

Nutritional supplementation and physical activity have been shown to positively influence muscle mass and strength in older adults. The efficacy of long-term nutritional supplementation in combination with physical activity in older adults remains unclear. Mobility-limited (short physical performance battery [SPPB] ≤9) and vitamin D insufficient (serum 25(OH) D 9-24 ng/mL) older adults were recruited for this study. All subjects participated in a physical activity program. Subjects were randomized to consume a daily nutritional supplement (150 kcal, 20 g whey protein, 800 IU vitamin D, 119 mL beverage) or placebo (30 kcal, nonnutritive, 119 mL). In a prespecified secondary analysis, we examined total-body composition (dual energy X-ray absorptiometry), thigh composition (computed tomography), and muscle strength, power, and quality before and after the 6-month intervention. One hundred and forty-nine subjects were randomized into the study [mean (standard deviation, SD) age 78.5 (5.4) years; 46.3% female; mean (SD) short physical performance battery 7.9 (1.2); mean (SD) vitamin D 18.7 (6.4) ng/mL]. After the intervention period both groups demonstrated improvements in muscle strength, body composition, and thigh composition. Nutritional supplementation lead to further losses of intermuscular fat (p = .049) and increased normal muscle density (p = .018). Six months of physical activity resulted in improvements in body composition, subcutaneous fat, intermuscular fat, and strength measures. The addition of nutritional supplementation resulted in further declines in intermuscular fat and improved muscle density compared to placebo. These results suggest nutritional supplementation provides additional benefits to mobility-limited older adults undergoing exercise training. ClinicalTrials.gov Identifier: NCT01542892.

Nutritional supplementation with physical activity improves muscle composition in mobility‐limited older adults, the VIVE2 study: a randomized, double‐blind, placebo‐controlled trial

BackgroundNutritional supplementation and structured physical activity have been shown to positively influence muscle mass and strength in older adults. The efficacy of long‐term nutritional supplementation in combination with structured physical activity in this population remains unclear.ObjectiveTo examine the effects of a combined intervention of nutritional supplementation and structured physical activity compared to a placebo, on measures of total‐body and thigh composition and knee extensor strength in a cohort of mobility‐limited older adults across two sites (Boston, MA, USA and Stockholm, Sweden).DesignMobility‐limited (Short Physical Performance Battery (SPPB) ≤9) and vitamin D insufficient (serum 25(OH) D 9 – 24 ng/ml) older adults were recruited for this study. All subjects participated in a physical activity program (3x/week for 24 weeks), involving walking, strength, balance, and flexibility exercises. Subjects were randomized consume a daily nutritional supplement (150kcal, 20g whey protein, 800IU vitamin D, 4 fl. oz. beverage) or placebo (30kcal, non‐nutritive). We examined total‐body composition (DXA), thigh composition (CT), and muscle strength, power, and quality before and after the 6‐month intervention.Results149 subjects were randomized into the study (mean age=77.5±5.4; female=46.3%; mean SPPB= 7.9±1.2; mean vitamin D=18.7±6.4 ng/ml). Adherence across supplement and placebo groups was similar for the physical activity intervention (75% and 72%, respectively) and the study product (86% and 88%, respectively). After the intervention period both groups demonstrated improvements in total‐body composition, subcutaneous fat, intermuscular fat, and strength measures. Nutritional supplementation lead to further losses of intermuscular fat (treatment effect: −0.33 cm2, 95% CI: −0.68 ~ 0.02), increased normal density muscle (treatment effect: 3.17 cm2, 95% CI: 0.52 ~ 5.83), and an increase in serum 25(OH)D (treatment effect: 4.55 ng/ml, 95% CI: 2.03 ~ 7.08).ConclusionsSix‐months of structured physical activity resulted in improvements in body composition, subcutaneous fat, intermuscular fat, and strength measures. The addition of nutritional supplementation resulted in a greater decline in intermuscular fat and improved muscle density. These results suggest nutritional supplementation provides additional benefits in mobility‐limited and vitamin D deficient older adults.Support or Funding InformationThis study was supported in part by Nestle' Health Science. In addition, this work was also supported by the U.S. Department of Agriculture (USDA), under agreement No. 58‐1950‐0‐014 and the Boston Claude D. Pepper Center Older American Independence Centers (OAIC; 1P30AG031679). Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the USDA.

Percutaneous endoscopic gastrostomy versus percutaneous radiological gastrostomy for swallowing disturbances.

Gastrostomy has been established as the standard procedure for administering long-term enteral nutrition in individuals with swallowing disturbances. Percutaneous gastrostomy is a less-invasive approach than open surgical gastrostomy, and can be accomplished via endoscopy (percutaneous endoscopic gastrostomy or PEG) or sonographic or fluoroscopic guidance (percutaneous radiological gastrostomy or PRG). Both techniques have different limitations, advantages, and contraindications. In order to determine the optimal technique for long-term nutritional supplementation many studies have been conducted to compare the outcomes of these two techniques; however, it remains unclear as to which method is superior to the other with respect to both efficacy and safety. To compare the safety and efficacy of PEG and PRG in the treatment of individuals with swallowing disturbances. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, January 2016); MEDLINE (1946 to 22 January 2016); EMBASE (1980 to 22 January 2016); the reference lists of identified articles; databases of ongoing trials, including the Chinese Cochrane Centre Controlled Trials Register; and PubMed. We applied no language restrictions. Randomised controlled trials (RCTs) comparing PEG with PRG in individuals with swallowing disturbances, regardless of the underlying disease. Two authors independently evaluated the search results and assessed the quality of the studies. Data analyses could not be performed as no RCTs were identified for inclusion in this review. We identified no RCTs comparing PEG and PRG for percutaneous gastrostomy in individuals with swallowing disturbances. The large body of evidence in this field comes from retrospective and non-randomised controlled studies and case series. Based on this evidence, both PEG and PRG can be safely performed in selected individuals, although both are associated with major and minor complications. A definitive RCT has yet to be conducted to identify the preferred percutaneous gastrostomy technique. Both PEG and PRG are effective for long-term enteral nutritional support in selected individuals, though current evidence is insufficient to recommend one technique over the other. Choice of technique should be based on indications and contraindications, operator experience and the facilities available. Large-scale RCTs are required to compare the two techniques and to determine the optimal approach for percutaneous gastrostomy.

Safety of dietary conjugated α-linolenic acid (CLNA) in a neonatal pig model

The aim of the present study was to perform a short-term safety evaluation of dietary mono-conjugated α-linolenic acid isomers (CLNA; c9-t11-c15-18:3+c9-t13-c15-18:3) using a neonatal pig model. CLNA diet was compared with three other dietary fats: (1) conjugated linoleic acid (CLA; c9-t11-18:2+t10-c12-18:2), (2) non-conjugated n-3 PUFA and (3) n-6 PUFA. Thirty-two piglets weaned at 3weeks of age were distributed into four dietary groups. Diets were isoenergetic and food intake was controlled by a gastric tube. Mono-CLNA diet did not significantly change body or organ weight, carcass composition and most biochemical parameters including; glucose, cholesterol, triglycerides, creatinine, blood urea nitrogen, hepatic enzymes and electrolytes levels in blood (P⩾0.09). Conversely, the n-3 PUFA composition of the brain, liver and heart decreased by 6–21% in the CLNA-fed group compared to animals fed nonconjugated n-3 PUFA (P<0.01). Responses to dietary treatments were tissue-specific, with the liver and the brain being the most deprived in n-3 PUFA. Our results support that short-term intake of mono-CLNA is safe in neonatal pigs but n-3 PUFA reduction in tissues deserves to be further investigated before using long-term nutritional supplementation in pigs and other animal models and before moving to clinical trials.

A case of severe chronic obstructive pulmonary disease who showed progressive weight loss in which long-term nutritional supplementation therapy was effective

A case of severe chronic obstructive pulmonary disease who showed progressive weight loss in which long-term nutritional supplementation therapy was effective

Amino Acid Supplementation Differentially Modulates STAT1 and STAT3 Activation in the Myocardium Exposed to Ischemia/Reperfusion Injury

We have previously demonstrated that the transcription factor STAT1 plays a critical role in promoting apoptotic cell death, whereas the related STAT3 family member may antagonize STAT1 and protect cardiac myocytes from ischemia/reperfusion (I/R) injury. More recently we demonstrated that long-term nutritional supplementation with mixed amino acids (AAs) can enhance myocyte survival by preserving mitochondrial functional capacity during I/R injury. We therefore investigated whether short-term nutritional supplementation with the same AA mixture has any effects on STAT1 or STAT3 activation in the Langendorff perfused rat heart exposed to I/R injury. In Sprague-Dawley rats given a single oral dose of a mixture of mainly essential l-AA (1 g/kg), and exposed, after 6 hours, to 35 minutes of ischemia, followed by 120 minutes of reperfusion, AA supplementation prolonged STAT3 activation/phosphorylation, while STAT1 activation was reduced. Enhanced STAT3 phosphorylation paralleled a reduction in expression of Fas, a known STAT1 target gene and proapoptotic marker that is upregulated after I/R. Moreover, abrogation of STAT3 activation by means of the JAK inhibitor AG490, reduced, but did not abolish, the cardioprotective effects of AA supplementation after I/R. These results show that modulation of the functional balance between STAT3 and STAT1, with preferential activation of prosurvival STAT3 over the proapoptotic STAT1, represents a mechanism by means of which short-term oral supplementation with mixed AAs protects the heart from I/R injury.

This month in gastroenterology

This month in gastroenterology

Nutritional supplementation with branched-chain amino acids in advanced cirrhosis: a double-blind, randomized trial

Background & aims: The role of oral supplementation with branched-chain amino acids (BCAA) in advanced cirrhosis is far from settled. A nutritional approach might prevent progressive liver failure and improve nutritional parameters and quality of life. Methods: A multicenter, randomized study comparing 1-year nutritional supplementation with BCAA against lactoalbumin or maltodextrins was performed in 174 patients with advanced cirrhosis. Primary outcomes were the prevention of a combined end point (death and deterioration to exclusion criteria), the need for hospital admission, and the duration of hospital stay. Secondary outcomes were nutritional parameters, laboratory data and Child-Pugh score, anorexia, health-related quality of life, and need for therapy. Results: Treatment with BCAA significantly reduced the combined event rates compared with lactoalbumin (odds ratio, 0.43; 95% confidence interval, 0.19–0.96; P = 0.039) and nonsignificantly compared with maltodextrins (odds ratio, 0.51; 95% confidence interval, 0.23–1.17; P = 0.108). The average hospital admission rate was lower in the BCAA arm compared with control treatments ( P = 0.006 and P = 0.003, respectively). In patients who remained in the study, nutritional parameters and liver function tests were, on average, stable or improved during treatment with BCAA and the Child-Pugh score decreased ( P = 0.013). Also, anorexia and health-related quality of life (SF-36 questionnaire) improved. Long-term compliance with BCAA was poor. Conclusions: In advanced cirrhosis, long-term nutritional supplementation with oral BCAA is useful to prevent progressive hepatic failure and to improve surrogate markers and perceived health status. New formulas are needed to increase compliance.

Bypassing The Oral Cavity: The Use of Tube Esophagostomy For Long-Term Enteral Nutritional Support In A Foal

Summary A premature foal developed severe aspiration pneumonia secondary to persistent dorsal displacement of the soft palate associated with marked edema of the larynx and nasopharynx. Tube esophagostomy was used successfully for long-term nutritional supplementation. There were no complications, and bypass of the larynx and pharynx allowed resolution of the palatal abnormality and subsequent resolution of the aspiration pneumonia. (Vet. Emerg. Crit. Care, 10:7–12, 2000)

The effect of disease, drug, and diet on whole body protein metabolism in adolescents with Crohn disease and growth failure

The effect of chronic inflammation, corticosteroid therapy, and nutritional supplementation on whole body protein metabolism and growth was determined in adolescent males with Crohn disease and growth failure. Body protein status was characterized in six patients and in five healthy, age-matched controls by nitrogen balance, whole body potassium (measured as 40K), urinary creatinine excretion, and [15N]glycine turnover studies. The patients subsequently received an intragastric nutritional supplement that increased dietary protein and energy intakes by 40% for seven months. Follow-up anthropometric measurements were obtained in both groups of adolescents. Our results demonstrated that lean body mass (40K) and muscle mass (creatinine) were significantly reduced in the patients compared to the controls, despite similar nitrogen balances between both groups. Whole body nitrogen flux, rates of protein synthesis and breakdown, and net protein retention were no different between those patients with chronic inflammation, while receiving corticosteroid therapy, and their controls. Long-term nutritional supplementation significantly improved linear and ponderal growth velocities in the patients such that growth rates were commensurate with those of the healthy controls. We conclude that chronic inflammation and corticosteroid therapy are not associated with detectable alterations in protein metabolic processes at the whole body level. Rather, dietary insufficiency appears to be primarily responsible for growth failure in adolescents with Crohn disease.