Diabetes and Atherosclerotic Vascular Disease- Nutraceutical Intervention Update

Alpha Lipoic Acid:  The incidence of type 2 diabetes mellitus (DM) in the U.S. is already high, and the rate is climbing rapidly. Medical complications seen in  DM patients include coronary heart disease, peripheral vascular disease, nephropathy, neuropathy and retinopathy. While control of blood sugar levels is of paramount importance, attention to the sequelae may reduce morbidity and help reduce healthcare costs.

Pivotal in the development of diabetic complications is dysfunction of vascular endothelia. Inflammation of the inner lining of the blood vessels results in platelet aggregation and deposition of cholesterol resulting in atherosclerotic plaque development.  The formation of atherosclerotic plaque is results directly from endothelial inflammation, often monitored by serum CRP levels.

Recently, it was observed that intravenous alpha lipoic acid (ALA), was found to be beneficial in patients with DM who suffer from endothelial dysfunction.(1) Forearm blood flow was measured before and after 21 days of either IV treatment of 600mg ALA or placebo. Intravenous ALA treatment improves endothelium-dependent vasodilatation.  The investigators also observed that LDL-cholesterol was reduced in the ALA treatment group.

It was postulated that ALA might improve endothelial function through inhibition of NF-kappa B and metalloproteinase-9 and upregulation of intracellular adhesion molecule-1 (ICAM-1).

Alpha Lipoic Acid may also be useful in the treatment of obesity, which is itself a risk factor for the development of DM.  At this time, 34 percent of adults aged 20 and older are obese; 34 percent are ‘overweight.’

In a recent study, ALA was studied for weight loss in ‘pre-obese’ and obese adults. Findings of a  recent study observing 1,127 men and women between the ages of 18 and 60 years, observations after measuring the BMI of all participants, 53 percent were found to be obese and 43 percent were pre-obese. Study participants were given ALA for 4 months at a dosage of 800mg per day.

The participants experienced After supplementation, investigators found that participants experienced an 8-9 percent reduction in body weight, a reduction in BMI by 2-4 points, and a reduction in waist size by 2.5-4 inches.(3)

Resveratrol:   Resveratrol is a naturally occurring  polyphenol found in the skin of red grapes and is found in red wine. Thought to offer a range of beneficial medical effects, Resveratrol is being studied for anti-cancer effects and for  cardiovascular benefits.

Recently, Resveratrol was studied (2) in patients given Resveratrol 40 mg, or placebo, for six weeks. In the Resveratrol group, there was a significant reduction in the generation of reactive oxygen species, binding of NF-κB (a major regulatory component of pro-inflammatory cytokine production), and expression of JNK-1 and Iκκβ (pro-inflammatory molecules). Study participants in the Resveratrol group had decreased levels of CRP, TNF-alpha and IL-6 (two major pro-inflammatory cytokines that are regulated by NF-κB.

According to the authors: “The extract induced a significant reduction in reactive oxygen species generation, the expression of p47(phox), intranuclear nuclear factor-kappaB binding, and the expression of jun-N-terminal kinase-1, inhibitor of kappaB-kinase-beta, phosphotyrosine phosphatase-1B, and suppressor of cytokine signaling-3 in mononuclear cells when compared with the baseline and the placebo. PCE intake also suppressed plasma concentrations of TNF-alpha, IL-6, and C-reactive protein.”

Whey Protein:  In a recent study, (4) the effects of supplemental dietary whey protein was observed in relation to body composition, lipids, insulin and glucose in comparison to casein and glucose (control) supplementation.  In this 12 week study, subjects were randomized to receive whey protein, casein or glucose supplementation.  Seventy men and women, mean ages of 48.4 (SEM 0.86) years and a mean BMI of 31.3 (SEM 0.8) kg/m2 completed the study. Subjects supplemented with whey protein had no significant change in body composition or serum glucose at 12 weeks compared with the control or casein group. Fasting glucose levels were significantly lowered in the whey group, as  compared with the control group at 6 weeks, and there was a significant decrease in total cholesterol and LDL cholesterol at week 12 in the whey group as compared with the casein receiving cadre. Fasting insulin levels were also significantly decreased in the whey group compared with the control group. Demonstrating that supplementation with whey proteins improves fasting lipids and insulin levels in overweight and obese individuals.

Recommendation:  Increasing scientific data support the use of Alpha Lipoic Acid and Resveratrol in the treatment of patients with type II Diabetes.  Available at reasonable cost, these two nutraceuticals are useful in the treatment of a variety of other conditions, as well, and afford the practitioner an additional modality to offer patients.

These two nutraceuticals are widely available, but should be used in conjunction with appropriate diet modification.

Alpha Lipoic Acid
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  1. Heinisch BB, Francesconi M, Mittermayer F, et al: Alpha-lipoic acid improves vascular endothelial function in patients with type 2 diabetes: a placebo-controlled randomized trial. Eur J Clin Invest 2010 Feb:40(2):148-54.
  2. Ghanim H, Sia CL, Abuayseh S, et al: An antiinflammatory and reactive oxygen species suppressive effects of an extract of Polygonum cuspidatum containing Resveratrol. J Clin Endocrinol Metab 2010 Sept;95(9):E1-8. .

3. Carbonelli MG, Di Renzo L, Bigioni M, et al:  Alpha-lipoic acid supplementation: a tool for obesity therapy? Curr Pharm Des.  2010;16(7):840-6.

  1. Pals S, Ellis V & Dhaliwal S: Effects of whey protein isolate on body composition, lipids, insulin and glucose in overweight and obese individuals. Br J Nutr. 2010 Sept; 104(5):716-23.
About David S Klein, MD 149 Articles
David S. Klein, MD, FACA, FACPM was born in Washington, DC, and was raised in Chevy Chase, Maryland. He completed his undergraduate education at the University of Maryland with degrees in Chemistry and Psychology. Medical School was completed at the University of Maryland at Baltimore, followed by Internship in General Surgery at the University of North Carolina and Residency in Anesthesiology at the Duke University, Durham, North Carolina. Dr Klein has been practicing medicine since 1983, concentrating in Pain Medicine, Minimally Invasive Medicine and Surgery, and Neuroendocrinology. Earning Board Certification in Anesthesiology, Dr. Klein was elected Fellow in the American College of Anesthesiology, and he was elected Fellow in the American College of Pain Medicine. He is currently an adjunct Associate Professor at the University of Central Florida, School of Medicine. He has focused his private practice on treating patients with hormone imbalance issues, nutritional deficiency related medical problems as well as pain related issues and impairment. With a highly-complex, CLIA licensed laboratory in-house, he has been able to provide rapid-turn around analysis efficiently and cost-effectively. Lecturing extensively nationally as well as internationally, Dr. Klein has authored many articles on topics relating to pain, injury and nutritionally modulated illness. His radio show, “Pain Free Living,” received top ratings during the 6 years it was on the air. Currently practicing in Longwood, Florida, Dr. Klein practices entirely in the office setting.