May 1, 2015

Salacia oblonga and Heart Disease

Ayurvedic botanical may decrease cardiovascular risk in kidney patients
Used for centuries in Ayurvedic medicine to treat diabetes, Salacia oblonga is now getting attention in the west. A recent study found it reduced the risk of cardiovascular disease in patients with chronic kidney failure.
Reference 
Singh RG, Rathore SS, Wani IA, Usha, Agrawal A, Dubey GP. Effects of Salacia oblonga on cardiovascular risk factors in chronic kidney disease patients: a prospective study. Saudi J Kidney Dis Transpl. 2015;26(1):61-66.

Design 

Randomized, prospective, placebo-controlled, single-blind study 

Participants

Sixty participants (46 men, 14 women) with chronic kidney disease (CKD), defined by a creatinine level between 1.5 mg/dL and 5.0 mg/dL, were evaluated. Patients were divided into 2 groups: Group A participants (n=30) had no diagnosis of diabetes. Group B (n=30) was comprised of diabetics (type 1 or 2 not specified). Each group was then evenly divided into an intervention arm (A1 and B1) and a placebo arm (A2 and B2). Almost all participants were between 40 and 60 years old. Those taking drugs targeting the renin-angiotensin system were excluded, as were those with signs or symptoms of acute renal failure.

Intervention

Salacia oblonga 1000 mg (1 g) twice daily: Although not stated, it is assumed this is 1000 mg of the root powder, in keeping with traditional use.

Outcome Measures

Parameters assessed included creatinine clearance (mL/min) as well as circulating levels of creatinine (mg/dL), cholesterol (mg/dL), triglycerides (mg/dL), high-density lipoprotein (HDL) cholesterol (mg/dL), low-density lipoprotein (LDL) cholesterol (mg/dL), C-reactive protein (CRP, mg/dL), and interleukin (IL)-6 (pg/dL). The mean for each parameter was calculated and comparisons calculated between arm A1 vs A2 and arm B1 vs B2.
 
At baseline, there were no statistically significant differences in any parameters between groups, indicating there was no bias in the randomization. The intervention arm, A1 or B1, was compared to its respective placebo arm, A2 or B2, in the statistical analysis. Groups A and B were not compared with each other.

Key Points 

At 6 months, triglycerides were 23.66% lower in the intervention arm of group A (nondiabetics) (P=0.008) and 17.45% lower in the intervention arm of Group B (diabetics) (P=0.01) vs their respective placebo arms. CRP was also statistically lower in the interventional arms of both groups vs placebo (Group A: 2.38±0.63 mg/dL to 1.76±0.59 mg/dL; P=.002 and Group B: 2.78±0.90 to 2.10±0.67; P=0.03). Finally, creatinine clearance did not improve but did stabilize in those taking S oblonga in both intervention groups (Group A, P=.05; Group B, P=0.04). Only the diabetics (Group B) had significant reductions in the inflammatory marker Il-6 (P=0.0003), total serum cholesterol levels (241.10±38.40 to 209.27±18.40; P=0.0001), and LDL levels (138.60±40.20 to 112.80±25.90; P=0.01) vs placebo.

Practice Implications

S oblonga is an obscure plant in Western botanical practice but has a long history of use in Ayurvedic medicine. One of its uses is in blood sugar control, presumably due to constituents that inhibit the brush boarder enzyme alpha-galactosidase. Blockage of alpha-galactosidase prevents monosaccharide production, leading to less carbohydrate absorption.1 This is the same mechanism of action that several diabetes drugs (acarbose, miglitol, voglibose) are based upon.
 
PubMed currently lists 37 studies on S oblonga, 4 of which are clinical trials. (One of those clinical trials is being reviewed here.) Other trials involve blood sugar control specifically. In short, the results are impressive.
 
In 2005, the glycemic and insulin responses to S oblonga were measured in 43 healthy, nondiabetic volunteers.2 After an overnight fast, a controlled meal (83 g carbohydrate, 20 g protein, and 14 g fat) was given to the participants, and serum glucose as well as insulin were tracked for 180 minutes. While the absolute peak of glucose did not vary, the area under the curve (AUC) did show significant change. When participants took 1000 mg S oblonga with the meal, there were reductions in the glucose AUC of 27% at 120 minutes (P=0.035). Perhaps more impressive, the AUC for insulin was reduced by 35% and 37% for 120 minutes and 180 minutes, respectively (P<0.001 each). The participants also underwent hydrogen breath testing, which increased 60% in those taking S oblonga (P<0.001), confirming the presence of undigested disaccharides and oligosaccharides in the small bowel. 
The current study under review indicates that Salacia oblonga is capable of improving cholesterol profiles as well as parameters of systemic inflammation in diabetics. 
Two of the 3 authors from that study published another separate clinical trial, also in 2005.3 The challenge meal was identical, the AUC for insulin and glucose was similarly tracked, and hydrogen breath testing was done after the test meal. This time, however, there was a dose escalation of S oblonga from 0 mg to 500 mg to 700 mg to 1000 mg. The participants included 39 healthy, nondiabetic, normal-weight volunteers. While the change in glucose AUC did not reach statistical significance, the AUC for insulin was reduced by 29% (P=.01). Excretion of hydrogen in the breath increased with increasing dosage of S oblonga, suggesting a dose-dependent increase in luminal oligosaccharides.
 
A randomized double-blind crossover study published in 2007 recruited 66 type 2 diabetics in an effort to test S oblonga in a population that may derive therapeutic benefit.4 After fasting 8 to 16 hours, subjects consumed the following meals on separate days: a high carbohydrate control meal (110 g carbohydrate [55 g maltodextrin, 31 g sucrose, 25 g corn syrup], 12 g fat, 18 g protein, and 620 kcal); the same control meal plus 240 mg S oblonga extract; or the same control meal plus 480 mg S oblonga extract. Both doses lowered the AUC for glucose (14% for 240 mg and 22% for 480 mg of S oblonga) compared to the control meal. Peak glucose was 19% lower and 27% lower for the 2 increasing dosages as compared to the control meal. The AUC for insulin was also reduced by 14% and 19% for the 240 mg and 480 mg intakes, respectively. Furthermore, peak insulin response was lowered with the use of S oblonga by 9% when 240 mg was ingested and 12% when 480 mg was ingested. The dose-response trends in this study strengthen the correlations in glucose and insulin reductions. 
 
There was also 1 clinical trial done on a different species of Salacia, S chinensis, in which 27 healthy volunteers participated. Only serum glucose was tracked. A high carbohydrate meal (macronutrients not specified, 600 kcal) combined with 1000 mg of S chinensis reduced postprandial glucose AUC by 33.85% vs placebo.5 In this trial, there was mild abdominal discomfort reported by some, including bloating, cramping, nausea, and diarrhea. 
 
Clinically, the potential of S oblonga to lead to abdominal discomfort seems high. Alpha-galactosidase is responsible for the breakdown of sugars in the gut. If alpha-galactosidase is inhibited, then undigested sugars remain in the lumen of the small intestine and colon. These undigested sugars are then metabolized by the gut flora, potentially forming gaseous byproducts like hydrogen that can lead to cramping, bloating, and/or nausea. Further, if the patient has small intestinal bacterial overgrowth (SIBO), symptoms of SIBO could worsen with inhibition of alpha-galactosidase. This is a clinical consideration that should be kept in mind. Instructions for the use of prescriptive alpha-galactosidase inhibitors include working up the dose slowly. This would be prudent for S oblonga as well.
 
It is a disservice to reduce any plant to a singular action such as an alpha-glucosidase inhibitor. However, the light of clinical research has been shone on this aspect, thus we have data in this area. As with any botanical, there are many actions from 1 plant. 
 
The current study under review indicates that S oblonga is capable of improving cholesterol profiles as well as parameters of systemic inflammation in diabetics. It appears to be the first clinical trial to corroborate the rodent studies that have indicated S oblonga has lipid-lowering and antiinflammatory effects.6,7 Cardiovascular disease (CVD) is still the number 1 cause of death in the United States, and those with CKD succumb to CVD at twice the rate of those without kidney impairment.8
 
The stabilization in kidney function parameters was found in diabetics and nondiabetics, suggesting S oblonga is relevant for our nondiabetic CKD patients as well. In herbal medicine, it would be deemed a kidney “tonic.” The ability to improve function, or tonify, a given organ with a plant is inherent in traditional herbal applications. Examples of this are adaptogenic herbs (eg, ginsengs, rhodiola, ashwagandha) for the hypothalamic-pituitary-adrenal axis or cardiac tonics such as hawthorn berries and/or leaves. These traditional uses now have evidence to back them up,9-11 but of course they have worked for centuries, long before such published evidence existed. 
 
Toxicology studies done on S oblonga have found no observable adverse effect level with 2500 mg/kg per day of oral gavage administrations to rats.12 There were also no reported untoward effects, save the abdominal discomfort already mentioned above, in the clinical trials to date. 
 
S oblonga has not been an herb in my repertoire for CKD patients. However, progressive kidney diseases are notoriously difficult to treat. After delving into the research on S oblonga, it is now on my short list of possible herbs for patients with diabetes and/or kidney failure.

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References

  1. Matsuda H, Yoshikawa M, Morikawa T, Tanabe G, Muraoka O. Antidiabetogenic constituents from Salacia species. J Tradit Med. 2005;22(Suppl 1):145-153.
  2. Collene AL, Hertzler SR, Williams JA, Wolf BW. Effects of a nutritional supplement containing Salacia oblonga extract and insulinogenic amino acids on postprandial glycemia, insulinemia, and breath hydrogen responses in healthy adults. Nutrition. 2005;21(7):848-854.
  3. Heacock PM, Hertzler SR, Williams JA, Wolf BW. Effects of a medical food containing an herbal alpha-glucosidase inhibitor on postprandial glycemia and insulinemia in healthy adults. J Am Diet Assoc. 2005;105(1):65-71.
  4. Williams JA, Choe YS, Noss MJ, Baumgartner CJ, Mustad VA. Extract of Salacia oblonga lowers acute glycemia in patients with type 2 diabetes. Am J Clin Nutr. 2007;86(1):124-130.
  5. Koteshwar P, Raveendra KR, Allan JJ, Goudar KS, Venkateshwarlu K, Agarwal A. Effect of NR-Salacia on post-prandial hyperglycemia: A randomized double blind, placebo-controlled, crossover study in healthy volunteers. Pharmacogn Mag. 2013;9(36):344-349.
  6. Ismail TS, Gopalakrishnan S, Begum VH, Elango V. Anti-inflammatory activity of Salacia oblonga Wall. and Azima tetracantha Lam. J Ethnopharmacol. 1997;56(2):145-152. 
  7. Huang TH, Yang Q, Harada M, et al. Salacia oblonga root improves cardiac lipid metabolism in Zucker diabetic fatty rats: modulation of cardiac PPAR-alpha-mediated transcription of fatty acid metabolic genes. Toxicol Appl Pharmacol. 2006;210(1-2):78-85.
  8. United States Renal Data System. Chapter 3: Morbidity & mortality. Available at: http://www.usrds.org/2014/view/v1_03.aspx. Accessed May 5, 2015.
  9. Panossian A, Wikman G. Evidence-based efficacy of adaptogens in fatigue, and molecular mechanisms related to their stress-protective activity. Curr Clin Pharmacol. 2009;4(3):198-219.
  10. Panossian A, Wikman G. Effects of adaptogens on the central nervous system and the molecular mechanisms associated with their stress-protective activity. Pharmaceuticals. 2010;3(1):188-224.
  11. Pittler MH, Schmidt K, Ernst E. Hawthorn extract for treating chronic heart failure: meta-analysis of randomized trials. Am J Med. 2002;114(8):665-674.
  12. Flammang AM, Erexson GL, Mirwald JM, Henwood SM. Toxicological and cytogenetic assessment of a Salacia oblonga extract in a rat subchronic study." Food Chem Toxicol. 2007;45(10):1954-1962.