10.31.07
New research on Chromium supplemention’s potential in the prevention of Type 2 Diabetes and Coronary Artery Disease
Here’s another federally-funded study of chromium supplementation to counter insulin resistance and potentially help prevent the development of Type 2 Diabetes and Coronary Artery Disease.
Investigator: Dr. UMESH MASHARANI, Univ. of California at San Francisco
Sponsor: NCCAM/National Institutes of Health
Abstract: DESCRIPTION (provided by applicant): Background: Chromium is an essential nutrient for the maintenance of normal glucose tolerance. While studies of chromium supplementation in patients with type 2 diabetes (T2D) have indicated that this agent lowers glucose and insulin levels, its cellular mechanism of action is not welt understood. Studies both in humans and in cell culture suggest that chromium enhances the insulin signaling pathway. We propose, therefore, to study chromium’s effects on insulin-stimulated glucose uptake in a well characterized population of non-obese, non-diabetic subjects with insulin resistantance. This population is ideal for an analysis of the effects of chromium on insulin action, because they are as insulin resistant as T2D patients but do not have the important confounder of hyperglycemia. Because these insulin resistant subjects are at risk for the development of T2D, the Metabolic Syndrome, and coronary artery disease (CAD), a demonstration of the beneficial effects of chromium on insulin action could ultimately have important public health consequences. Hypotheses: (1) Chromium will improve insulin sensitivity in a general population of non-obese, insulin-resistant, non-diabetic subjects; and (2) The improvement of insulin action by chromium is due to its effects on the major components of the insulin signling pathway (insulin receptor, IRS proteins, PI 3-kinase, PKB/AKT and GLUT4); and/ or regulators of the insulin signaling pathway (PTP 1B, PC-1, IKK, NF-KappaB and PKC) Methods: The insulin sensitivity of 180 subjects will be initially estimated by homeostasis model assessment. The most insulin resistant subjects will then be randomized to 16 weeks of therapy with either chromium or placebo. To quantitate chromium-induced improvements in both in insulin sensitivity and the insulin signaling pathway, euglycemic hyperinsulinemic clamps with muscle biopsies will be performed before and after treament. Anticipated Results and Significance: We believe these studies will (1) confirm the beneficial effect of chromium on insulin sensitvity; (2) further our understanding of the molecular mechanisms of chromium action; and (3) form a basis for a larger project examining the long term efficacy of chromium in preventing the developement of T2D and CAD.
10.30.07
Novel Therapy for Glucose Intolerance in HIV Disease (Chromium picolinate)
This research is being funded by NCCAM, the federal government’s chief dietary supplement research agency. It builds on past knowledge about the role of an inexpensive dietary supplement, chromium, for management of diabetes (insulin resistance/glucose intolerance). This research study is directed especially to the case of people with HIV on multi-drug regimens, who experience insulin resistance/glucose intolerance at a high rate.
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Investigator: Dr. Marie C Gelato, State University of New York at Stony Brook
Abstract: DESCRIPTION (provided by applicant): Multi-drug regimens in HIV disease are associated with an incidence of insulin resistance of at least 50%. Insulin resistance is associated with the development of dyslipidemia, type 2 diabetes, and hypertension. This constellation of metabolic abnormalities is known to cause accelerated atherosclerosis in patients with type 2 diabetes. The current guidelines from the American Diabetes Association and the American College of Endocrinologists recommends screening for glucose intolerance and treatment for patients at high risk of diabetes. This proposal seeks to establish a treatment option for insulin resistance / glucose intolerance in HIV/AIDS prior to the transition to overt diabetes. Chromium picolinate is a dietary supplement that has been shown to improve insulin sensitivity in patients with type 2 diabetes mellitus and, in a preliminary study, in HIV+ patients. This dietary supplement has a wide margin of safety and may provide substantial therapeutic benefit without serious side-effects. This proposal will test the hypothesis that chromium picolinate improves insulin-stimulated glucose uptake by increasing the insulin receptor-mediated tyrosine phosphorylation of insulin receptor substrate-1, resulting in increased activity of phosphatidylinositol 3-kinase. The hypothesis will be addressed in two specific aims. Specific Aim 1 will assess quantitative improvements in insulin-mediated glucose disposal in a double-blind, placebo-controlled study of chromium supplementation with 1000 microgram (19.2 mu/mol) of chromium as chromium picolinate, over a two month course of therapy of subjects with glucose intolerance (defined with an oral glucose tolerance test, OGTT). Both safety and efficacy (improved glucose disposal with a hyperinsulineminc, euglycemic clamp and insulin secretion, OGTT) will be evaluated. The cellular mechanism for improved insulin sensitivity with chromium supplementation will be determined in Specific Aim 2 by assessing the effect of chromium supplementation on the insulin-stimulated activity of insulin receptor substrate-1-associated phosphatidylinositol 3-kinase in biopsies of adipose tissue. Thus, this research will document the therapeutic benefit of chromium supplementation for insulin resistance / glucose intolerance in HIV disease and will provide a mechanistic framework to explain how chromium supplementation enhances insulin action.
10.29.07
Probiotics, soluble fiber, and L-glutamine (LGN) reduce nelfinavir (NFV)- or lopinavir / ritonavir (LPV / r)-related diarrhea
Here’s an article from 2004.
Note the combination of probiotics, soluble fiber, and glutamine used:
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Carla R. Heiser, MS, RD, LD Center for Functional Nutrition, Advocate Illinois Masonic Medical Center, Chicago, Illinois, USA ; Judith A. Ernst, DMSc, RD Indiana University, Indianapolis, Indiana, USA; James Tom Barrett, MD Howard Brown Health Center, Advocate Illinois Masonic Medical Center, Chicago, Illinois, USA; Neel French, MD and Malte Schutz, MD Howard Brown Health Center, Advocate Illinois Masonic Medical Center, Chicago, Illinois, USA; Michael P. Dube, MD Indiana University, Indianapolis, Indiana, USA
Purpose: Highly active antiretroviral therapy (HAART) can be associated with diarrhea and other gastrointestinal (GI) side effects. Reducing these side effects may improve treatment durability and quality of life (QOL). This study assessed the impact of nutritional co-therapies known to reduce diarrhea in HIV-positive men treated with nelfinavir (NFV)- or lopinavir/ritonavir (LPV/r)-containing regimens. Methods: Thirty-five HIV-positive men treated with NFV (n = twenty-seven) or LPV/r (n = eight) with diarrhea (± two liquid stools/day [d]) participated in a 12-week prospective study. Twenty-eight subjects were randomly assigned supplements (S), seven received standard of care (C). Group S received probiotics (1.2g/d) and soluble fiber (11g/d). If diarrhea persisted at week 4, 30g/d L-Glutamine (GLN) was added. Diarrhea incidence, as well as supplement and antidiarrheal use, was assessed monthly. Results: Weight, CD4 count, and HIV RNA were unchanged in both groups. Diarrhea completely resolved in 10 of 28 (36 percent) S subjects. The mean (± SD) number of stools/d declined [3.40 ± 1.25 to 2.54 ± 1.34 (p < 0.01)]. Diarrhea (loose, watery stools/d) lessened in S from 2.84 ± 1.42 to 0.74 ± 1.03 (p < 0.0001). Fifteen S subjects did not obtain full relief with probiotics and fiber, but stools/d decreased from 4.08 ± 1.35 to 3.06 ± 1.68 (p < 0.05) after starting GLN. In C, stools/d, 4.14 ± 4.86 to 3.44 ± 1.68(p = 0.678) and incidence of diarrhea/d, 3.00 ± 4.82 to 1.36 ± 1.29 (p= 0.361) was unchanged. In S, loperamide use decreased from 1.69 ± 2.34 to 0.31 ± 0.69 mg/d (p < 0.01); 18 versus eight subjects used loperamide at 0 and 12 weeks, respectively. Conclusion: Probiotics, soluble fiber, and GLN significantly reduced diarrhea for subjects receiving NFV or LPV/r. Nutritional co-therapies show clinical benefit in HIV-positive men with diarrhea.
Citation: J Int Assoc Physicians AIDS Care (Chic Ill) 3: 121-129
Statins and people with HIV: overview of special concerns
This information from www.aidsmap.com provides a good overview of the special concerns involved in the prescription of cholesterol-lowering statins for people with HIV. (Note: references to the scientific literature in this piece may be retrieved by going back to the aidsmap website.)
You may want to read this information together with our posts on Niacin +statins, an emerging standard of care for cholesterol control (see under Niacin on this Blog).
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Atorvastatin (Lipitor) is a statin that can reduce the levels of low-density lipoprotein (LDL or ‘bad’) cholesterol in the blood. This can reduce the risk of cardiovascular disease, including heart attacks and strokes. Statins work by inhibiting the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, which is responsible for the production of cholesterol.
Patients with liver disease or who are pregnant should not take statins. However, they are safe drugs in most patients. The main side-effects are muscle pain, as well as headache, altered liver function, tingling sensations, abdominal pain, flatulence, constipation, diarrhoea, nausea and vomiting.
Statins, including atorvastatin, are effective in the treatment of the alterations of blood fat levels due to treatment with anti-HIV drugs, particularly protease inhibitors. However, atorvastatin is broken down by the cytochrome P450 3A4 enzyme, and interacts with all available protease inhibitors and non-nucleoside reverse transcriptase inhibitors (NNRTIs).
Protease inhibitors cause an increase in atorvastatin levels, increasing the risk of side-effects such as muscle pain and damage to the muscle fibres. Consequently, patients taking protease inhibitors should use another statin such as pravastatin sodium (Lipostat) or fluvastatin (Lescol) in place of atorvastatin, or they should use the lowest possible dose of atorvastatin with caution.
In contrast, NNRTIs reduce the levels of atorvastatin, putting patients at risk of poor anti-cholesterol effects. Patients taking an NNRTI and atorvastatin should have their dose of atorvastatin adjusted as required to keep cholesterol levels low.
Some experts believe that statins may have anti-HIV properties in their own right. However, a recent study found that atorvastatin failed to prevent CD4 cell count declines in patients interrupting anti-HIV treatment.
L-carnitine and HIV
Here’s a brief extract on “L-Carnitine and HIV,” as presented by www.aidsmap.com, the website of NAM*, the UK-based HIV/AIDS information exchange.
L-carnitine suppresses the production of tumour necrosis factor, which is responsible for wasting in HIV-positive people. Patients taking L-carnitine have reported reduced fatigue and greater energy.A six-month study of carnitine supplementation also significantly reduced the frequency of CD4 and CD8 T-cell death and produced higher CD4 cell counts. There is substantial evidence from an Italian research group that L-carnitine inhibits HIV-related cell death by targeting the immune system rather than the virus itself.
* From the www.aidsmap.com website: NAM is an award-winning, community-based organisation, which works from the UK. We deliver reliable and accurate HIV information across the world to HIV-positive people and to the professionals who treat, support and care for them. NAM is a UK registered charity number 1011220.
NAM’s publications are evidence-based and reviewed by two international medical panels and one of HIV-positive people, which ensure accuracy, balance, relevance, and accessibility.
10.26.07
Low blood levels of Vitamin D associated with higher risk of acute respiratory tract infections
A study published in the American Journal of Clinical Nutrition, September 2007, found a significant relationship between lower levels of Vitamin D and respiratory infections.
The study population was 800 young Finnish men (military conscripts), who were followed over a six-month period. Those with lower blood levels of Vitamin D had about twice as many days out due to respiratory tract infections as their counterparts with higher levels of the vitamin.
NYBC commentary: Still another demonstration of the health benefits associated with Vitamin D. Of course, this was not a study of Vitamin D supplementation, so scientifically speaking, it cannot properly yield a recommendation to take Vitamin D in order to reduce your risk of respiratory infection. But given the strength of this finding, it’s very probable that further investigations on this topic will follow, with the aim of defining any benefit that may come from taking Vitamin D supplements to ward off respiratory tract infections.
10.25.07
Massachusetts General, Butler Hospital testing SAMe for depression treatment: Promising nutritional supplement being compared with SSRI, placebo
This news release was accessed by us on the Massachusetts General Hospital website.
We noted with interest that the sponsor of this five-year study is the National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health–the principal dietary supplement research agency of the US government. NYBC has followed earlier, promising studies of SAMe as an anti-depressant, and we’re glad that there is now a significant research project underway to further investigate the properties of this molecule as a treatment for depression.
Mass. General, Butler Hospitals testing SAMe for depression treatment:
Promising nutritional supplement being compared with SSRI, placebo
BOSTON/PROVIDENCE- June 26, 2007 – Massachusetts General Hospital (MGH), in collaboration with Butler Hospital in Providence, is currently undertaking a clinical trial examining the effectiveness of the nutritional supplement S-adenosyl methionine (SAMe) as a treatment for depression.
A naturally occurring substance found in every human cell, SAMe is known to play a role in the synthesis of serotonin and other brain chemicals involved in the regulation of mood. Nutritional supplements containing SAMe have been used to treat depression, and more than 45 clinical studies have suggested that it may be as effective as the older tricyclic antidepressants for some patients. Current studies, like the MGH/Butler trial, are focused on comparing SAMe with the newer selective serotonin reputake inhibitor (SSRIs) antidepressants.
“SAMe appears to be a promising treatment for depression,” says David Mischoulon, MD, PhD, of the MGH Department of Psychiatry, one of the trial’s investigators. “It’s looking like SAMe supplementation may allow the body to maintain higher levels of critical neurotransmitters that could reverse a depressed state.” Mischoulon is an assistant professor of Psychiatry at Harvard Medical School.
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The five-year trial is designed to test the safety, effectiveness and tolerability of SAMe compared with the SSRI escitalopram (Lexapro) or a placebo…
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Note: an overview of information on SAMe, including recommendations concerning B-complex supplementation for those taking this supplement, is available on the NYBC website:
10.22.07
Fish and Omega-3 Fatty Acids: American Heart Association Recommendation
This recommendation appears on the website of the American Heart Association:
Omega-3 fatty acids benefit the heart of healthy people, and those at high risk of — or who have — cardiovascular disease. We recommend eating fish (particularly fatty fish) at least two times a week. Fish is a good source of protein and doesn’t have the high saturated fat that fatty meat products do. Fatty fish like mackerel, lake trout, herring, sardines, albacore tuna and salmon are high in two kinds of omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).To learn about omega-3 levels for different types of fish — as well as mercury levels, which can be a concern — see our Encyclopedia entry on Fish, Levels of Mercury and Omega-3 Fatty Acids.We also recommend eating tofu and other forms of soybeans, canola, walnut and flaxseed, and their oils. These contain alpha-linolenic acid (LNA), which can become omega-3 fatty acid in the body. The extent of this modification is modest and controversial, however. More studies are needed to show a cause-and-effect relationship between alpha-linolenic acid and heart disease.The table below is a good guide to use for consuming omega-3 fatty acids.Summary of Recommendations for Omega-3 Fatty Acid Intake
| Population | Recommendation |
| Patients without documented coronary heart disease (CHD) | Eat a variety of (preferably fatty) fish at least twice a week. Include oils and foods rich in alpha-linolenic acid (flaxseed, canola and soybean oils; flaxseed and walnuts). |
| Patients with documented CHD | Consume about 1 g of EPA+DHA per day, preferably from fatty fish. EPA+DHA in capsule form could be considered in consultation with the physician. |
| Patients who need to lower triglycerides | 2 to 4 grams of EPA+DHA per day provided as capsules under a physician’s care. |
Patients taking more than 3 grams of omega-3 fatty acids from capsules should do so only under a physician’s care. High intakes could cause excessive bleeding in some people.
Background
In 1996 the American Heart Association released its Science Advisory, “Fish Consumption, Fish Oil, Lipids and Coronary Heart Disease.” Since then important new findings have been reported about the benefits of omega-3 fatty acids on cardiovascular disease. These include evidence from randomized, controlled clinical trials. New information has emerged about how omega-3 fatty acids affect heart function (including antiarrhythmic effects), hemodynamics (cardiac mechanics) and arterial endothelial function. These findings are outlined in our November 2002 Scientific Statement, “Fish Consumption, Fish Oil, Omega-3 Fatty Acids and Cardiovascular Disease.”
The ways that omega-3 fatty acids reduce CVD risk are still being studied. However, research has shown that they
- decrease risk of arrhythmias, which can lead to sudden cardiac death
- decrease triglyceride levels
- decrease growth rate of atherosclerotic plaque
- lower blood pressure (slightly)
What do epidemiological and observational studies show?
Epidemiologic and clinical trials have shown that omega-3 fatty acids reduce CVD incidence. Large-scale epidemiologic studies suggest that people at risk for coronary heart disease benefit from consuming omega-3 fatty acids from plants and marine sources.
The ideal amount to take isn’t clear. Evidence from prospective secondary prevention studies suggests that taking EPA+DHA ranging from 0.5 to 1.8 grams per day (either as fatty fish or supplements) significantly reduces deaths from heart disease and all causes. For alpha-linolenic acid, a total intake of 1.5–3 grams per day seems beneficial.
Randomized clinical trials have shown that omega-3 fatty acid supplements can reduce cardiovascular events (death, non-fatal heart attacks, non-fatal strokes). They can also slow the progression of atherosclerosis in coronary patients. However, more studies are needed to confirm and further define the health benefits of omega-3 fatty acid supplements for preventing a first or subsequent cardiovascular event. For example, placebo-controlled, double-blind, randomized clinical trials are needed to document the safety and efficacy of omega-3 fatty acid supplements in high-risk patients (those with type 2 diabetes, dyslipidemia, hypertension and smokers) and coronary patients on drug therapy. Mechanistic studies on their apparent effects on sudden death also are needed.
Increasing omega-3 fatty acid intake through foods is preferable. However, coronary artery disease patients may not be able to get enough omega-3 by diet alone. These people may want to talk to their doctor about taking a supplement. Supplements also could help people with high triglycerides, who need even larger doses. The availability of high-quality omega-3 fatty acid supplements, free of contaminants, is an important prerequisite to their use.
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For NYBC’s fish oil supplement, see the product description for Jarrow’s Max DHA.
And we add some general dietary advice about fat:
Remember that the balance of fats you eat is the first, most important step to consider. Dump the hydrogenated fats (found in cookies, margarine and lots of things; read labels!), limit saturated fat intake (dairy, red meat, fried stuff) and increase good fat intake (deep sea fish like salmon, tuna; olive oil, hemp oil, etc.) Lastly: in controlling cholesterol through modifications in diet, it’s not always emphasized enough that sugar intake will also influence your cholesterol levels!
NYBC Offers a Low-Cost Alternative to K-PAX
K-PAX, a multi-supplement pack, was developed following Dr. Jon Kaiser’s study that found an increase in CD4 count among HIV+ individuals using this mix of a potent multivitamin and antioxidants. (Dr. Kaiser was hardly new to the field of nutritional supplementation for people with HIV/AIDS—see his book Healing HIV: How To Rebuild Your Immune System, which was based on many years of clinical experience with hundreds of patients and still, in our judgment, has many valuable insights about everything from assessing and managing gastrointestinal problems, to exercise and diet for people with HIV.)
At this point, the Medicaid or ADAP formularies of many states include the K-PAX formula. Unfortunately, some people may not have access to these programs and for them, cost can become an issue. For example, the price for the double strength K-PAX formula is about $140 per month, not an insignificant amount for anyone on a budget and dealing with the usual extra healthcare-related costs. That’s why NYBC has designed an alternative to the double-strength K-PAX formula, based on products and prices currently available through our nonprofit purchasing coop. Here’s our suggestion, which is not a precise, 100% match of the K-PAX, but does, we feel, provide a close equivalent–and at a much lower cost:
Acetylcarnitine – 3/day – one month supply = $15.50 (one bottle; 500mg/90)
Lipoic – one/day – one month supply = $7.50 half a bottle; 300mg/60)
NAC – 3/day – one month supply = $11.25 (one bottle; 500mg/90)
Vit B6 (pyridoxal-5’-phosphate/P5P) – 3/day – one month supply = $7.85 (one bottle; 50mg/100)
Vit B12 (methylcobalamin) – 2/day – one month supply = $3.75 (actually, les than half a bottle; 1000mg/100)
Added Protection (or Ultra Preventive Beta) – 6/day – one month supply = $14.00 ($17.00 for UPB) (one bottle; 180)
Total monthly cost of the NYBC multivitamin-antioxidant package is $59.85. (The intial cost, since you use only half a bottle to make a monthly supply of some items, is $71.10.) This is HALF THE PRICE of the double-strength K-PAX. Notes: 1) The NYBC package actually has MORE acetylcarnitine than the double-strength K-PAX—not a bad idea, especially if you believe, as we do, that acetylcarnitine is probably one of the key elements in the multivitamin-antioxidant combination. (Two a day is probably sufficient if you’re just interested in matching the K-PAX formula, but three or more can help if you’re dealing with neuropathy.)
2) The multivitamins available through NYBC have somewhat different formulas than the K-PAX (see product labels available on the NYBC website for details). Taking an extra vitamin C tab along with the regular multi would make up for one significant difference. And some might wish to take a bit more calcium and vitamin D3 than Added Protection offers, as bone loss remains a concern among people with HIV.
3) K-PAX only comes with iron; for those with liver trouble, this might NOT be a good idea. With the multivitamin Added Protection, you can choose whether to take iron or not. And Ultra Preventive Beta, another Douglas Labs multi, offers in addition to a standard multivitamin formula a variety of food-based nutrients, for an additional $3 per month. If you’d like more information on NYBC’s low-cost alternative to K-PAX, or if you’d like help in ordering the alternative package, please email us at contact@newyorkbuyersclub.org and we’d be glad to assist.
10.18.07
Niacin and cholesterol control: National Library of Medicine/NIH Review
Here’s the review of Niacin for cholesterol control from Medline Plus, a service of the National Library of Medicine/National Institutes of Health. Note the caution for those with Type 2 diabetes.
Niacin is a well-accepted treatment for high cholesterol. Multiple studies show that niacin (not niacinamide) has significant benefits on levels of high-density cholesterol (HDL or “good cholesterol”), with better results than prescription drugs such as “statins” like atorvastatin (Lipitor®). There are also benefits on levels of low-density cholesterol (LDL or “bad cholesterol”), although these effects are less dramatic. Adding niacin to a second drug such as a statin may increase the effects on low-density lipoproteins.The use of niacin for the treatment of dyslipidemia associated with type 2 diabetes has been controversial because of the possibility of worsening glycemic control. Patients should check with a physician and pharmacist before starting niacin.
Reference: http://www.nlm.nih.gov/medlineplus/druginfo/natural/patient-niacin.html
See also NYBC’s description of Niacin 100mg and Niacin 400mg. These are timed-release formulas; also provided are guides for minimizing the “flushing” that can accompany niacin use.
NAC (N-acetylcysteine) as antidote to acetaminophen toxicity
Here’s more information on NAC as an antidote to acetaminophen overdose (best-known tradename is Tylenol, but note that acetaminophen is often paired with other drugs).
emedicine work-up on “acetaminophen toxicity”, including the role of NAC as antidote:
Frequency:
• In the US: Acetaminophen is the drug most commonly ingested in overdoses and is a common co-ingestant. Acetaminophen-induced hepatic failure is the second leading cause of liver transplantation.
Mortality/Morbidity:
• Since the introduction of NAC, the mortality rate from APAP toxicity is low.However, in its Nov. 29, 2005 edition, The New York Times reported alarm among some in the healthcare community about a rise in acetaminophen poisoning in the US. NYBC replied in a letter to the Editor:
[We were] surprised that your article “Poisonings From a Popular Pain Reliever Are on the Rise” (Nov. 29, 2005) did not mention a readily available antidote for acute acetaminophen poisoning: N-acetylcysteine (NAC), a dietary supplement that costs just a few dollars. NAC has been studied and used as an antidote to acetaminophen overdose in Europe, and more recently in the US as well. It would be too bad if your article alerted people to the dangers of overdosing on this pain reliever without mentioning the wide availability and effectiveness of the antidote.
To conclude: we fear that this may be still another case of the prevalent bias in the US healthcare community against dietary supplements, dictated frequently by pharmaceutical companies’ lack of interest in promoting low-cost, low-margin supplements (as opposed to patentable and thus highly lucrative medications). The result: while in Europe acetaminophen poisoning risk is decreased by its usual pairing with NAC in drugs, in the US this pairing is less common, with the disastrous consequences outlined in The New York Times article.
See additional NAC information on the NYBC website: NAC -Pharmaceutical Grade.
