Water and Blueberries - but not B vitamins - for Risk Reduction
Another summer has past, and the days here in the Pacific NW are getting shorter and wetter. This season is excellent for writing, hunkered down in a warm sweater with a good cup of tea! Over the last six months, several clinical trials have been published relevant to integrative approaches to diabetes care and/or cardiovascular disease risk reduction that I would like to share with you in this article. Included are summaries of several new studies suggesting select B vitamins may not be helpful in serious kidney disease - and may actually increase the development of diabetic kidney disease! However, several food-derived natural products performed very well in recent clinical trials including dried blueberry powder. Finally I'll finish by summarizing a recent clinical trial of water (yes, water) for weight loss! I hope that you or a friend finds this article helpful in a path toward optimal health.
B Vitamins in Kidney Disease - Two Strikes
About three years ago I wrote a two articles reviewing the available clinical trials of B vitamins in diabetes and vascular concerns related to diabetes (See here and here). Much of the research at that time focused on clinical trials that studied B vitamins folic acid, vitamin B12 and vitamin B6 for homocysteine-lowering. As mentioned then, although this combination of B vitamins was effective at lowering homocysteine in the blood, this lowering did not reduce the risk for having a significant vascular event, including unstable angina, heart attack and death (the jury is still our on whether these B vitamins reduce risk for stroke). However because homocysteine and other biomarkers of impaired vascular function are very elevated in patients with kidney disease, additional clinical trials were performed evaluating the promise of B vitamin supplementation in this particular subgroup of patients, i.e. patients with kidney disease and homocysteine elevations. Unfortunately the results are not promising.
Dr. Andrew House, MD et al. recently published a clinical trial performed in five hospitals in Canada evaluating folic acid, vitamin B12, and vitamin B6 to reduce diabetic kidney disease.1 238 patients with diabetes and proteinuria (protein in the urine, a hallmark of diabetic kidney disease) were randomized to receive 2.5 mg/day of folic acid, 25 mg/day of vitamin B6, and 1 mg/day of vitamin B12 or matching placebo. To evaluate the change in kidney function and overall effect on cardiovascular risk, the investigators measured the filtration rate of the kidneys (called glomerular filtration rate, or GFR), new cases requiring dialysis and composite risk of heart attack, stroke, number of revascularization procedures and all causes of death. Following nearly three years of treatment with folic acid, vitamin B12, and vitamin B6, the participants in the B vitamin group had greater reductions in their filtration rate, i.e. a worsening of kidney function, than did the placebo group! Also alarming is that although new cases of dialysis were not different between the groups, the B vitamin group also had a higher risk of heart attack, stroke, revascularization, or death than did the placebo group. Although it wasn't crystal clear which element(s) of this composite outcome was responsible for this difference, the greatest difference was in the incidence of stroke, in which six participants in the B vitamin group had a stroke, compared to only one participant in the placebo group.
Also published within the past few months was a much larger clinical trial by Heinz et al. performed in 650 patients with end-stage kidney disease undergoing dialysis in 33 dialysis centers across Germany2. This study evaluated high-dose B vitamins (5 mg folic acid, 50 micrograms of B12, and 20 mg of B6) compared to a very low dose of B vitamins considered "placebo" treatment (0.2 mg folic acid, 4 micrograms B12, and 1.0 mg of B6) for differences in death and cardiovascular events between the groups. In this study, the B vitamins were given to each patient three times per week, at the dialysis center immediately following dialysis treatment. Although this trial did not show any increase in death or significant cardiovascular event, it did not demonstrate any reduction using high-dose B vitamin treatment.
The combined impact of these recent clinical trials of B vitamins in renal disease, along with past clinical trials demonstrating no reduction of significant events from homocysteine lowering, has led me to reconsider routine supplementation with folic acid, vitamin B12 and/or vitamin B6. Although I have never prescribed B vitamins to all patients, I was once a believer in the homocysteine hypothesis, and now I typically no longer order this blood test. Additionally, based on the results of the study of House et al. I now recommend that patients stop supplementation with folic acid, vitamin B12 and vitamin B6 if they have any suggestion of kidney disease (i.e. borderline GFR or protein in their urine).
Although these recent studies have impacted my practice, and my overall perception of the safety and efficacy of B vitamin supplementation, I still maintain that not all B vitamins are treated equally and it is important to not make sweeping generalizations about B vitamin supplementation in all people. For example, vitamin B12 has substantial evidence suggesting benefit for diabetic neuropathy and thiamine (and thiamine derivatives) has preliminary evidence suggesting benefits in kidney disease, as well as in neuropathy. More research is certainly needed to inform providers and patients alike about the safety and effectiveness of these approaches. In the meantime, if you take B vitamin supplements, including a B complex, I encourage each of you to discuss this choice with your physician, especially if you have any suggestion of kidney disease.
Go Blue! Blueberries Lower Cardiometabolic Risk
In other exciting research news, blueberries are getting the attention they deserve! One of my teachers, and co-founder of Bastyr University in Seattle, WA, Dr. Bill Mitchell, ND used to tell our class that the first thing he would tell his patients with diabetes is to eat a cup of frozen blueberries every morning (then again he was also known for consuming large spoonfuls of bright yellow quercetin powder and grinning like he just ate a canary!). Although he explained that the blue pigmented compounds in the berry skin were particularly helpful to the blood vessels in diabetes, little else was offered in terms of the mechanism of this action, or the overall effects of this "treatment" suggestion for patients. Well, now many old naturopathic recommendations are receiving the research they deserve, and so is the case for blueberries.
Two recent clinical trials have evaluated freeze-dried blueberries for effect on cardiometabolic risk parameters, including blood pressure, insulin sensitivity and oxidative stress biomarkers. The first by Basu et al. randomized forty-eight patients with metabolic syndrome to either a 50g-dried blueberry beverage or placebo beverage per day.4 Following 8 weeks of supplementation, both systolic and diastolic blood pressure, oxidized LDL cholesterol, and biomarkers of fat oxidation were substantially lower in the blueberry group compared to the control group!
The second clinical trial of blueberries is even more exciting. Stull et al. performed a randomized clinical trial to determine if dried blueberry powder mixed into a smoothie would alter insulin sensitivity in thirty-two obese patients without diabetes, but with established insulin resistance.5 The blueberry powder used was the same as the product used by Basu et al, and the daily dose is equivalent to 2 cups of fresh blueberries per day. Following just six weeks of supplementation, insulin sensitivity was substantially improved in the blueberry group compared to the placebo group. However, despite this improvement in insulin sensitivity, there were no changes in blood sugar, blood cholesterol, or inflammatory biomarkers.
Although these studies were not performed in patients with diabetes, insulin resistance and high blood pressure are hallmark features of diabetes, and given no detrimental effects were observed from the blueberry powder, I think these results could be extrapolated to patients with diabetes. One important consideration is the sugar content of blueberries, however. 1 cup of blueberries contains about 14grams of sugar, or less than one medium-sized apple which is about 19 grams of sugar. Substituting one or two servings of blueberries per day in place of refined carbohydrates like breads, pastas, or rice will not only provide more fiber and other healthful vitamins and minerals, but also important polyphenol compounds that may help lower your blood pressure, reduce oxidative stress, and improve your sensitivity to insulin!
Water: The Elixir of Life
Now on to more promising news, including the most essential element of life: water. There are lots of beliefs out there about water, and few of them supported by science- except the science of common sense! I think it is a pretty safe assumption that if you don't drink water - which comprises 40-60% of your body's total weight - bad things will happen. Given that most laboratory measures are reported as a concentration, it also seems obvious that by increasing your blood volume, you are likely to reduce this concentration, according to the old chemistry tenant "dilution is the solution to pollution" whether the "pollution" is blood glucose or some detoxification product (but then, I am also a believer in the tenant "You either use a water filter or you are a water filter"). However, it is also important to give patients accurate advice regarding water, and not over - or under - state the benefits of water intake, or type of water to drink etc.
Interestingly we are starting to see water and water intake as a subject of medical research. Recently, Dennis et al. published a clinical trial of water intake for weight loss.3 Specifically they randomized overweight and obese patients to a reduced calorie diet or a reduced calorie diet plus approximately two 8 ounce glasses of water before each daily meal. Outcome measures included weight loss as well as total caloric intake for each meal. After 12 weeks, the water group had lost 2 kilograms (~2.2 pounds) more on average and ate fewer calories during each meal. So next time you sit down to a large family meal, start with a glass of water or two...you might find the experience, well, re-hydrating!
The plight continues to find effective therapies to reduce risk for diabetes and the complications of diabetes. Although the rate of research is slow, and (in my opinion) a disproportionate amount of research funding still goes to drug development and high-tech interventions compared to health promotion and public health improvements, occasionally research gets performed on more deserving, yet less conventional, health practices. Although the results from recent studies of folic acid, vitamin B12 and vitamin B6 are not promising for routine use of these supplements (especially for kidney disease and for those at risk of kidney disease), promising results occasionally emerge for other health practices that do not require drugs and expensive tests. So this month, instead of refilling your B vitamin supplement, invest instead in blueberries, dried or otherwise, and before you eat them, have a glass of water!
In health- Ryan Bradley, ND, MPH
Ryan Bradley, ND, MPH is a naturopathic doctor, clinical researcher and epidemiologist in San Diego, CA. He is an Associate Professor and Assistant Director of Research at the National University of Natural Medicine in Portland, OR and an Assistant Professor in the Department of Family Medicine and Public Health at the University of California, San Diego.
- House AA, Eliasziw M, Cattran DC, et al. Effect of B-vitamin therapy on progression of diabetic nephropathy: a randomized controlled trial. JAMA;303:1603-9.
- Heinz J, Kropf S, Domrose U, et al. B vitamins and the risk of total mortality and cardiovascular disease in end-stage renal disease: results of a randomized controlled trial. Circulation;121:1432-8.
- Dennis EA, Dengo AL, Comber DL, et al. Water consumption increases weight loss during a hypocaloric diet intervention in middle-aged and older adults. Obesity (Silver Spring);18:300-7.
- Basu A MD, Leyva MJ, Sanchez K, Betts, NM, Wu M, Aston CE, Lyons TJ. Blueberries Decrease Cardiovascular Risk in Obsese Men and Women with Metabolic Syndrome. The Journal of Nutrition 2010;140:1582-7.
- Stull AJ CK, Johnson WD, Champagne CM, Cefalu WT. . Bioactives in Blueberries Improve Insuln Sensitivity in Obsese, Insulin-Resistant Men and Women. The Journal of Nutrition 2010;140:1764-8.