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Dietary macronutrient composition for weight loss and weight maintenance

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Summary: When designing a dietary strategy for weight loss and maintenance the individual patient’s functional and genetic constitution must be carefully considered, but there is an accumulation of evidence indicating that a high protein, low carbohydrate regimen is a good starting point.

There is a large body of evidence that can instruct us in how to fashion an eating plan to promote both short and long-term success in weight loss and healthy body composition. As a paper published in the journal Obesity demonstrates, the way many Americans eat—referred to as a ‘cafeteria diet’ (CF)—is worse than a diet high in lard. The authors note:

“Obesity has reached epidemic proportions worldwide and reports estimate that American children consume up to 25% of calories from snacks. Several animal models of obesity exist, but studies are lacking that compare high-fat diets (HFD) traditionally used in rodent models of diet-induced obesity (DIO) to diets consisting of food regularly consumed by humans, including high-salt, high-fat, low-fiber, energy dense foods such as cookies, chips, and processed meats.”

They investigated the effects on weight gain and inflammation of a cafeteria diet (CAF) compared to a lard-based 45% HFD by feeding their rodent models either HFD, CAF or a chow control for 15 weeks. Their data clearly show that even consuming almost half the diet in lard is better than the lethal mix that many now consume:

“Body weight increased dramatically and remained significantly elevated in CAF-fed rats compared to all other diets. Glucose- and insulin-tolerance tests revealed that hyperinsulinemia, hyperglycemia, and glucose intolerance were exaggerated in the CAF-fed rats compared to controls and HFD-fed rats.”

Moreover, the cafeteria diet was markedly worse in promoting inflammation:

“It is well-established that macrophages infiltrate metabolic tissues at the onset of weight gain and directly contribute to inflammation, insulin resistance, and obesity. Although both high fat diets resulted in increased adiposity and hepatosteatosis, CAF-fed rats displayed remarkable inflammation in white fat, brown fat and liver compared to HFD and controls. In sum, the CAF provided a robust model of human metabolic syndrome compared to traditional lard-based HFD, creating a phenotype of exaggerated obesity with glucose intolerance and inflammation.”

A study published in The New England Journal of Medicine examined specific dietary factors that stand out in their contribution to obesity noting that they…

“…may affect the success of the straightforward-sounding strategy “eat less and exercise more” for preventing long-term weight gain.”

They performed investigations involving 120,877 U.S. women and men who were free of chronic diseases and not obese at baseline for as long as twenty years. Relationships between changes in lifestyle factors and weight change were evaluated every four years. There were several factors that stood out:

“Within each 4-year period, participants gained an average of 3.35 lb. On the basis of increased daily servings of individual dietary components, 4-year weight change was most strongly associated with the intake of potato chips (1.69 lb), potatoes (1.28 lb), sugar-sweetened beverages (1.00 lb), unprocessed red meats (0.95 lb), and processed meats (0.93 lb) and was inversely associated with the intake of vegetables (−0.22 lb), whole grains (−0.37 lb), fruits (−0.49 lb), nuts (−0.57 lb), and yogurt (−0.82 lb)…Other lifestyle factors were also independently associated with weight change, including physical activity (−1.76 lb across quintiles); alcohol use (0.41 lb per drink per day), smoking (new quitters, 5.17 lb; former smokers, 0.14 lb), sleep (more weight gain with <6 or >8 hours of sleep), and television watching (0.31 lb per hour per day).”

Potatoes are clearly ‘sugar grenades’, but in my opinion further studies are required to examine the difference between red meat from animals treated with hormones and fed a grain diet versus those that are free of growth-stimulating medications and eat mainly grass.

With the most egregious insults to a metabolically healthy diet out of the way, we can proceed to the roles of glycemic index and glycemic load on weight loss as examined in a study published recently in the Journal of Nutrition:

“This study assessed the effect of changes in glycemic index (GI) and load (GL) on weight loss and glycated hemoglobin (HbA1c) among individuals with type 2 diabetes beginning a vegan diet or diet following the 2003 American Diabetes Association (ADA) recommendations.”

99 subjects with type 2 diabetes were randomized to follow 1 of 2 diet treatments for 22 weeks. Glycemic index and glycemic load changes were assessed and their relationships with changes in weight and HbA1C were calculated. (Glycemic index is a metric for rate which a food will cause blood sugar to rise. Glycemic load is determined by multiplying the glycemic index by the amount of carbohydrate in grams provided by a food and dividing the total by 100; this amounts to the sum of the glycemic loads for all foods consumed in the diet.) Interestingly, glycemic index predicted weight gain while glycemic load did not:

“…the vegan group reduced GI to a greater extent than the ADA group, but GL was reduced further in the ADA than the vegan group. GI predicted changes in weight, adjusting for changes in fiber, carbohydrate, fat, alcohol, energy intake, steps per day, group, and demographics, such that for every point decrease in GI, participants lost ~0.2 kg (0.44 lb)…Weight loss was a predictor of changes in HbA1C. GL was not related to weight loss or changes in HbA1C.”

Thus glycemic index takes precedence over glycemic load in choosing foods for weight loss and blood sugar regulation. Also notable was the finding regarding GI and HbA1C:

“GI was not a predictor for changes in HbA1C after controlling for weight loss.”

Every wonder why a patient’s HbA1C didn’t go down even though they were eating a low GI diet? This shows that if they don’t lose weight as a result, the the HbA1C will tend to stay the same. The authors conclude:

“A low-GI diet appears to be one of the determinants of success of a vegan or ADA diet in reducing body weight among people with type 2 diabetes. The reduction of body weight, in turn, was predictive of decreasing HbA1C.”

The interesting difference between the effects of glycemic index and glycemic load revealed here help to explain the inconsistency noted in a review published earlier in journal IUBMB (International Union of Biochemistry and Molecular Biology) Life:

“Recently, due to its possible link to appetite control and metabolism, several clinical studies have assessed the effect of low glycemic index (GI) and glycemic load (GL) diets on weight loss. To determine the application of GI/GL in the prevention and treatment of obesity, we searched several databases and identified 23 clinical trials that examined low GI/GL diets and weight loss as the primary outcome measure.”

Here the pooling of GI and GL seems to have obfuscated the issue. The authors conclude:

“Over the past decade, the body of research that links low GI/GL diets to weight loss has grown rapidly and significantly. While there is a significant amount of inconsistency in the current findings, the majority of studies found a trend that favored low GI/GL diets in weight loss.”

Moreover…

“…the benefits of low GI and GL diets extend beyond weight loss and have favorable effects on obesity-related risk factors such as heart disease and diabetes by mechanisms that are independent of weight loss.”

What about protein versus carbohydrate for weight loss? A number of investigators have examined this question, but an interesting study published recently in the Nutrition Journal corrects some important limitations in earlier work:

“Studies have suggested that moderately high protein diets may be more appropriate than conventional low-fat high carbohydrate diets for individuals at risk of developing the metabolic syndrome and type 2 diabetes. However in most such studies sources of dietary carbohydrate may not have been appropriate and protein intakes may have been excessively high. Thus, in a proof-of-concept study we compared two relatively low-fat weight loss diets – one high in protein and the other high in fiber-rich, minimally processed cereals and legumes – to determine whether a relatively high protein diet has the potential to confer greater benefits.”

They eighty-three overweight or obese women to either a moderately high protein (30% protein, 40% carbohydrate) diet (HP) or to a high fiber, relatively high carbohydrate (50% carbohydrate, > 35 g total dietary fiber, 20% protein) diet (HFib) for 8 weeks. During that time their energy intakes were reduced by 478 to 955 calories per day to achieve weight loss of between 0.5 and 1 kg per week. Which diet resulted in better weight loss?

“Participants on both diets lost weight (HP: -4.5 kg and HFib: -3.3 kg), and reduced total body fat (HP: -4.0 kg and HFib: -2.5 kg, and waist circumference (HP: -5.4 cm and HFib: -4.7 cm), as well as total and LDL cholesterol, triglycerides, fasting plasma glucose and blood pressure. However participants on HP lost more body weight (-1.3 kg) and total body fat (-1.3 kg). Diastolic blood pressure decreased more on HP (-3.7 mm Hg).”

High protein wins out over high carbohydrate, even when the carbohydrate is high fiber. The authors conclude:

“A realistic high protein weight-reducing diet was associated with greater fat loss and lower blood pressure when compared with a high carbohydrate, high fiber diet in high risk overweight and obese women.”

Importantly, the benefits of a high protein to carbohydrate ratio diet include the slowing of tumor growth and prevention of cancer initiation as described in an excellent paper (you may wish to read it in its entirety) published recently in the journal Cancer Research. It includes a significant consideration for reducing carbohydrate by increasing protein rather than fat. The authors state:

“Since cancer cells depend on glucose more than normal cells, we compared the effects of low carbohydrate (CHO) diets to a Western diet on the growth rate of tumors in mice. To avoid caloric restriction–induced effects, we designed the low CHO diets isocaloric with the Western diet by increasing protein rather than fat levels because of the reported tumor-promoting effects of high fat and the immune-stimulating effects of high protein.”

They were able to formulate diets that demonstrated that the tumor inhibiting effects were due to factors other than weight loss from calorie restriction (CR):

“To exploit the fact that cancer cells rely more heavily on glycolysis than normal cells, we designed low CHO, high protein diets to see if we could limit BG and tumor growth. In designing our diets, we wanted to avoid NCKDs [no calorie ketogenic diets] because of the difficulty in achieving long-term compliance with no CHO diets in potential future human studies and because Masko and colleagues recently reported that a 10% or 20% CHO diet slows tumor growth as effectively as NCKDs. Following early studies with 8% CHO diets, using 10% and 15% CHO, high protein diets in which 70% of the CHO was in the form of amylose, we found that, compared with a Western diet, they were indeed capable of reducing BG, insulin, and lactate levels and, importantly, in slowing the growth of implanted murine and human tumors, with little or no effects on mouse weight.”

There is good reason to apply these finding to human case management:

“Consistent with the notion that reducing BG in humans can be beneficial, there is a wealth of epidemiologic evidence showing a clear association between BG and/or insulin levels (which are determined by BG levels) and the incidence of human cancers. Thus, although our studies were conducted, out of necessity, with mice, the fact that human BG can be significantly reduced with low CHO diets and the association of many cancers with high BG levels suggest that our findings are very likely relevant to human cancers as well, particularly in cancers that have been associated with higher baseline BG and/or insulin levels, such as pancreatic, breast, colorectal, endometrial, and esophageal cancers.”

This also has application to prostate cancers:

“In addition to these cancers, a low CHO diet may also be beneficial in early-stage prostate cancer, even though it is not typically detectable by PET. This is because the metastases of these tumors kill the patients and, given the pivotal role of lactate in promoting metastasis, our low CHO diets could significantly reduce metastasis by reducing tumor-associated lactate levels.”

Regarding concerns about the impact on kidney function…

“In terms of macronutrient composition, even though high protein has been shown to promote satiety—thus reducing obesity, BG, and insulin levels—and enhance both antitumor immunity, through amino acid supplementation, and life span, we were concerned, based on the literature, that high protein levels might cause kidney damage. More recent data, however, suggest that this may only occur in individuals with existing chronic kidney disease and that in normal people, the increase in glomerular filtration rate and kidney cellularity that occur with long-term high protein consumption may be a normal response.”

Incidentally, amylose starch prevents DNA damage in the colon that may otherwise be caused by red meat:

“Interestingly, colonic cancer-inducing damage caused by red meats may be avoided with high amylose, low CHO diets. These studies suggest that macronutrient sources and combinations are very important…”

The authors conclude:

“Our study, herein, shows that a high amylose containing low CHO, high protein diet reduces BG, insulin, and glycolysis, slows tumor growth, reduces tumor incidence, and works additively with existing therapies without weight loss or kidney failure. Such a diet, therefore, has the potential of being both a novel cancer prophylactic and treatment, warranting further investigation of its applicability in the clinic, especially in combination with existing therapies.”

Regarding weight loss, what if exercise is added to the program? Will high protein still beat high carbohydrate. A study published in the journal The Physician and Sports Medicine studies this question as the authors set out to…

“…determine whether sedentary obese women with elevated levels of homeostatic model assessment (HOMA) insulin resistance (ie, > 3.5) experience greater benefits from an exercise + higher-carbohydrate (HC) or carbohydrate-restricted weight loss program than women with lower HOMA levels.”

221 women who participated in a 10-week supervised exercise and weight loss program were assigned low-fat (30%) diets that consisted of 1200 kcals per day for 1 week (phase 1) and 1600 kcals per day for 9 weeks (phase 2) with either high carbohydrate (HC) or higher protein (HP). Fasting blood samples, body composition, anthropometry, resting energy expenditure, and fitness measurements were obtained at the beginning and end. Again we see high protein win out over high carbohydrate:

“Subjects in the HP group experienced greater weight loss (−4.4 ± 3.6 kg vs −2.6 ± 2.9 kg), fat loss (−3.4 ± 2.7 kg vs −1.7 ± 2.0 kg), reductions in serum glucose (3% vs 2%), and decreases in serum leptin levels (−30.8% vs −10.8%) than those in the HC group.”

The authors conclude:

“A carbohydrate-restricted diet promoted more favorable changes in weight loss, fat loss, and markers of health in obese women who initiated an exercise program compared with a diet higher in carbohydrate. Additionally, obese women who initiated training and dieting with higher HOMA levels experienced greater reductions in blood glucose following an HP diet.”

Regarding the use of vegetable or fruit juices in programs designed for weight loss, a study published in the journal Obesity demonstrates that this is counter-productive:

“Beverage consumption has been implicated in weight gain, but questions remain about the veracity of the association, whether the relationship is causal and what property of beverages is responsible. It was hypothesized that food form is the most salient attribute. Thus, a randomized controlled trial of food form was conducted. Energy-matched beverage or solid forms of fruits and vegetables were provided to 34, lean or overweight/obese adults for two 8-week periods with a 3-week washout interspersed.”

During the solid food arm of the study the lean group had no significant weight change while the overweight/obese group had weight gain, but during the juice phase…

“In contrast, incomplete dietary compensation and weight gain occurred in both the lean (43%) and overweight/obese (61%) groups during the beverage arm…These data demonstrate energy consumed as beverages may be especially problematic for weight gain.”

And for the carbohydrates that are consumed, a curious study also published in Obesity offers evidence that eating them mainly at dinner further aids in weight loss, satiety and more:

“This study was designed to investigate the effect of a low-calorie diet with carbohydrates eaten mostly at dinner on anthropometric, hunger/satiety, biochemical, and inflammatory parameters. Hormonal secretions were also evaluated. Seventy-eight police officers (BMI >30) were randomly assigned to experimental (carbohydrates eaten mostly at dinner) or control weight loss diets for 6 months. On day 0, 7, 90, and 180 blood samples and hunger scores were collected every 4 h from 0800 to 2000 hours. Anthropometric measurements were collected throughout the study.”

Amazingly…

“Greater weight loss, abdominal circumference, and body fat mass reductions were observed in the experimental diet in comparison to controls. Hunger scores were lower and greater improvements in fasting glucose, average daily insulin concentrations, and homeostasis model assessment for insulin resistance (HOMAIR), T-cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels were observed in comparison to controls. The experimental diet modified daily leptin and adiponectin concentrations compared to those observed at baseline and to a control diet.”

Wow…all that just from shifting carbohydrates to dinner. The authors conclude:

“A simple dietary manipulation of carbohydrate distribution appears to have additional benefits when compared to a conventional weight loss diet in individuals suffering from obesity. It might also be beneficial for individuals suffering from insulin resistance and the metabolic syndrome.”

The scientific data addressing various aspects of dietary fat is treated in a separate post, but it’s suitable here to consider a study published in The Journal of Clinical Endocrinology & Metabolism offering evidence that a low carbohydrate diet is equivalent to a low fat diet for weight loss:

“Overweight and obese men and women (24–61 yr of age) were recruited into a randomized trial to compare the effects of a low-fat (LF) vs. a low-carbohydrate (LC) diet on weight loss…Subjects on the LF diet consumed an average of 17.8% of energy from fat, compared with their habitual intake of 36.4%, and had a resulting energy restriction of 2540 kJ/d [585 calories]. Subjects on the LC diet consumed an average of 15.4% carbohydrate, compared with habitual intakes of about 50% carbohydrate, and had a resulting energy restriction of 3195 kJ/d [763 calories].”

At the end of the study period the LC group lost as much weight and had better insulin regulation:

“Both groups of subjects had significant weight loss over the 10 wk of diet intervention and nearly identical improvements in body weight and fat mass. LF subjects lost an average of 6.8 kg and had a decrease in body mass index of 2.2 kg/m2, compared with a loss of 7.0 kg and decrease in body mass index of 2.1 kg/m2 in the LC subjects. The LF group better preserved lean body mass when compared with the LC group; however, only the LC group had a significant decrease in circulating insulin concentrations.”

The authors conclude:

“”These data suggest that energy restriction achieved by a very LC diet is equally effective as a LF diet strategy for weight loss and decreasing body fat in overweight and obese adults.”

Bottom line: When designing a dietary strategy for weight loss and maintenance the individual patient’s functional and genetic constitution must be carefully considered (inflammation, immune regulation, insulin sensitivity, allergy, intestinal permeability, sleep disordered breathing and hormonal function are fundamentals); but there is an accumulation of evidence suggesting that a high protein, low carbohydrate regimen is a good starting point.

The advantages of intermittent versus continuous calorie restriction for long term weight loss

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There is an accumulation of fascinating scientific evidence that intermittent calorie restriction (ICR) offers a number of advantages over continuous calorie restriction (CCR) for successful long term weight loss and the ‘turning on’ of genes that favor longevity. Consider a study published recently in the International Journal of Obesity in which the investigators compared ICR and CCR for weight loss and metabolic disease risk markers in overweight women. The authors state:

“Excess weight and weight gain during adult life increases the risk of several diseases including diabetes, cardiovascular disease (CVD), dementia, certain forms of cancer including breast cancer, and can contribute to premature death. Observational and some randomised trials indicate that modest weight reduction (>5% of body weight) reduces the incidence and progression of many of these diseases. Although weight control is beneficial, the problem of poor compliance in weight loss programmes is well known.”

Moreover…

“Even where reduced weights are maintained, many of the benefits achieved during weight loss, including improvements in insulin sensitivity, may be attenuated due to non-compliance or adaptation. Sustainable and effective energy restriction strategies are thus required.”

In other words, a method that can be comfortable enough to be accepted into daily life for the long that also avoids loss of improvements due to adaption is required.

“One possible approach may be intermittent energy restriction (IER), with short spells of severe restriction between longer periods of habitual energy intake. For some subjects such an approach may be easier to follow than a daily or continuous energy restriction (CER) and may overcome adaption to the weight reduced state by repeated rapid improvements in metabolic control with each spell of energy restriction.”

So the authors set out to…

“…compare the feasibility and effectiveness of IER with CER for weight loss, insulin sensitivity and other metabolic disease risk markers…This is the largest randomised comparison of an isocalorific intermittent vs. continuous energy restriction to date in free living humans..”

They designed a randomised comparison of a 25% energy restriction as IER (~2266 kJ/day which equals 541 calories per day for 2 days/week) or CER (~6276 kJ/day equaling 1499 calories each day for 7 days/week) in 107 overweight or obese premenopausal women for a 6 month study period. They measured an extensive list of biomarkers at baseline and after 1, 3 and 6 months: weight, anthropometry (size, weight and proportions), biomarkers for breast cancer, diabetes, cardiovascular disease and dementia risk; insulin resistance (HOMA), oxidative stress markers, leptin, adiponectin, IGF-1 and IGF binding proteins 1 and 2, androgens, prolactin, inflammatory markers (high sensitivity C-reactive protein and sialic acid), lipids, blood pressure and brain derived neurotrophic factor. What did the data show?

“Last observation carried forward analysis showed IER and CER are equally effective for weight loss, mean weight change for IER was −6.4 kg vs. −5.6 kg for CER. Both groups experienced comparable reductions in leptin, free androgen index, high sensitivity C-reactive protein, total and LDL cholesterol, triglycerides, blood pressure and increases in sex hormone binding globulin, IGF binding proteins 1 and 2. Reductions in fasting insulin and insulin resistance were modest in both groups, but greater with IER than CER; difference between groups for fasting insulin −1.2 μU/ml, and insulin resistance −1.2 μU/mmol/L.”

Regarding concerns about tolerance…

“A recent blinded trial of a 2 day VLCD [very low calorie diet] (1311 kJ/day [313 calories per day!]) reported no adverse effects on cognition, energy levels, sleep or mood, suggesting symptoms are expected with VLCD and therefore experienced and could potentially be overcome with appropriate counselling. Importantly IER did not lead to overeating on non-VLCD days.”

The authors briefly summarize the results of their comparison of IER and CER by concluding:

“IER is as effective as CER in regards to weight loss, insulin sensitivity and other health biomarkers and may be offered as an alternative equivalent to CER for weight loss and reducing disease risk.”

That’s not all though. The authors additionally note an extremely interesting observation with profound implications and potential for benefit regarding additional benefits of an intermittent very low calorie method:

“Recent reviews speculate that IER may be associated with greater disease prevention than CER due to increased cellular stress resistance, in particular increased resistance to oxidative stress. This is thought to be mediated by ‘hormesis’ whereby the moderate stress of energy restriction increases the production of cytoprotective, restorative proteins, antioxidant enzymes and protein chaperones. Alternate day fasting has been linked to increased SIRT-1 gene expression in muscle, and to greater neuronal resistance to injury compared to CER in C57BL/6 mice. The tendency for greater improvements in oxidative stress markers in our IER than in the CER group may support these assertions. Declines in long term protein oxidation product aggregates suggest IER as a possible activator of catabolism and autophagy.”

In other words, intermittent calorie restriction can be as effective as continuous calorie restriction for weight loss, but have the added advantage of ‘turning on’ genes beneficial for health and longevity and preventing adaptation that would result in regaining weight.

Other investigators also have compared intermittent with continuous calorie (daily) calorie restriction as in a study published recently in the journal Obesity Reviews. The authors set out to…

“…evaluate and compare the effects of daily CR versus intermittent CR on weight loss, fat mass loss, lean mass retention and visceral fat mass reduction, in overweight and obese adults.”

They undertook a review of studies that were randomized control trials, had a primary endpoint of weight loss and/or body composition changes, used daily CR or intermittent CR as the primary focus of the intervention; had a study duration of 4–24 weeks, and involved adult populations who were overweight or obese subjects but not diabetic. These included 11 daily continuous calorie restriction trials and five intermittent CR trials published between 2000 and 2010, along with two unpublished trials of intermittent CR from their own lab. What did all these studies add up to?

“Results reveal similar weight loss and fat mass loss with 3 to 12 weeks’ intermittent CR (4–8%, 11–16%, respectively) and daily CR (5–8%, 10–20%, respectively). In contrast, less fat free mass was lost in response to intermittent CR versus daily CR.”

This is a significant advantage of ICR over CCR (continuous = daily calorie restriction). The authors conclude by stating:

“In sum, intermittent CR and daily CR diets appear to be equally as effective in decreasing body weight, fat mass, and potentially, visceral fat mass. However, intermittent restriction regimens may be superior to daily restriction regimens in that they help conserve lean mass at the expense of fat mass. These findings add to the growing body of evidence showing that intermittent CR may be implemented as another viable option for weight loss in overweight and obese populations.”

Numerous other studies have examined the distinctive benefits of intermittent calorie restriction. A paper published recently in the journal Oncogene investigates the positive effects of brief ICR compared to CCR for cancer patients. The authors state:

“The dietary recommendation for cancer patients receiving chemotherapy, as described by the American Cancer Society, is to increase calorie and protein intake. Yet, in simple organisms, mice, and humans, fasting—no calorie intake—induces a wide range of changes associated with cellular protection, which would be difficult to achieve even with a cocktail of potent drugs. In mammals, the protective effect of fasting is mediated, in part, by an over 50% reduction in glucose and insulin-like growth factor 1 (IGF-I) levels.”

They point out that cancer cells are unable to respond to the positive stimuli of calorie restriction:

“Because proto-oncogenes function as key negative regulators of the protective changes induced by fasting, cells expressing oncogenes, and therefore the great majority of cancer cells, should not respond to the protective signals generated by fasting, promoting the differential protection (differential stress resistance) of normal and cancer cells.”

Moreover…

“Preliminary reports indicate that fasting for up to 5 days followed by a normal diet, may also protect patients against chemotherapy without causing chronic weight loss. By contrast, the long-term 20 to 40% restriction in calorie intake (dietary restriction, DR), whose effects on cancer progression have been studied extensively for decades, requires weeks–months to be effective, causes much more modest changes in glucose and/or IGF-I levels, and promotes chronic weight loss in both rodents and humans.”

They go on to review studies on fasting, cellular protection and chemotherapy resistance, and futher compare them to those on continuous calorie restriction and cancer treatment. The authors conclude:

“Although additional pre-clinical and clinical studies are necessary, fasting has the potential to be translated into effective clinical interventions for the protection of patients and the improvement of therapeutic index.”

A study published in the Journal of Molecular and Cellular Cardiology offers evidence that intermittent calorie restriction activates genes that help in the recovery from heart damage. The authors state:

“Chronic heart failure (CHF) is the major cause of death in the developed countries. Calorie restriction is known to improve the recovery in these patients; however, the exact mechanism behind this protective effect is unknown. Here we demonstrate the activation of cell survival PI3kinase/Akt and VEGF pathway as the mechanism behind the protection induced by intermittent fasting in a rat model of established chronic myocardial ischemia (MI).“

Two weeks after myocardial ischemia was induced in their study animals, they were randomly assigned to a normal feeding group (MI-NF) and an alternate-day feeding group (MI-IF). After 6 weeks the authors evaluated the effect of intermittent fasting on cellular and ventricular remodeling and long-term survival. The results were truly striking:

“Compared with the normally fed group, intermittent fasting markedly improved the survival of rats with CHF (88.5% versus 23% survival). The heart weight body weight ratio was significantly less in the MI-IF group compared to the MI-NF group (3.4 ± 0.17 versus 3.9 ± 0.18. Isolated heart perfusion studies exhibited well preserved cardiac functions in the MI-IF group compared to the MI-NF group. Molecular studies revealed the upregulation of angiogenic factors such asHIF-1-α (3010 ± 350% versus 650 ± 151%), BDNF (523 ± 32% versus 110 ± 12%), and VEGF (450 ± 21% versus 170 ± 30%) in the fasted hearts. Immunohistochemical studies confirmed increased capillary density in the border area of the ischemic myocardium and synthesis VEGF by cardiomyocytes. Moreover fasting also upregulated the expression of other anti-apoptotic factors such as Akt and Bcl-2 and reduced the TUNEL positive apoptotic nuclei in the border zone.”

This is a dramatic indication that intermittent calorie restriction can be used to protect and repair heart tissue. The authors conclude:

“Chronic intermittent fasting markedly improves the long-term survival after CHF by activation through its pro-angiogenic, anti-apoptotic and anti-remodeling effects.”

Another fascinating study published recently in the journal Cancer Prevention Research demonstrates that intermittent calorie restriction is clearly superior to both continuous calorie restriction and an unrestricted diet for breast cancer prevention. Specifically, the authors studied…

“The effect of chronic (CCR) and intermittent (ICR) caloric restriction on serum adiponectin and leptin levels…in relation to mammary tumorigenesis.”

Their subjects were assigned to ad libitum fed, ICR (3-week 50% caloric restriction followed by 3-wks 100% AL consumption), and CCR groups.

“Mammary tumor incidence was 71.0%, 35.4%, and 9.1% for AL, CCR, and ICR mice, respectively. Serum adiponectin levels were similar among groups with no impact of either CCR or ICR. Serum leptin level rose in AL mice with increasing age but was significantly reduced by long-term CCR and ICR. The ICR protocol was also associated with an elevated adiponectin/leptin ratio. In addition, ICR-restricted mice had increased mammary tissue AdipoR1 expression and decreased leptin and ObRb expression compared with AL mice. Mammary fat pads from tumor-free ICR-mice had higher adiponectin expression than AL and CCR mice whereas all tumor-bearing mice had weak adiponectin signal in mammary fat pad.”

This amounts to an impressive ‘turning on’ of genes that protect against breast cancer for ICR. In conclusion…

“…we did find that reduced serum leptin and elevated adiponectin/leptin ratio were associated with the protective effect of intermittent calorie restriction.”

A paper published in the journal Nutrition and Cancer demonstrates that ICR offers a greater protective effect than CCR for prostate cancer. The authors state:

“Prostate cancer is the most frequently diagnosed cancer in men. Whereas chronic calorie restriction (CCR) delays prostate tumorigenesis in some rodent models, the impact of intermittent caloric restriction (ICR) has not been determined. Here, transgenic adenocarcinoma of the mouse prostate (TRAMP) mice were used to compare how ICR and CCR affected prostate cancer development.”

Their animal models for prostate cancer were assigned to ad libitum (AL), ICR, and CCR groups. There were distinctive differences according to the manner of calorie restriction that dramatically favored the ICR over both the AL and CCR cohorts:

“ICR mice were older at tumor detection than AL and CCR mice. There was no difference for age of tumor detection between AL and CCR mice. Similar results were found for survival. Serum leptin, adiponectin, insulin, and IGF-I were all significantly different among the groups.”

Not only did the subjects on CCR live longer with healthier biomarkers than the ones on either the free diet or CCR, there was no difference between the AL and CCR groups for age of tumor detection or survival. The implication is exciting: the benefits were due not to the weight loss component but to the way in which ICR affects gene expression. The authors conclude:

“These results indicate that the way in which calories are restricted impacts both time to tumor detection and survival in TRAMP mice, with ICR providing greater protective effect compared to CCR.”

A paper published in the The Journal of Nutritional Biochemistry also offers evidence that intermittent calorie restriction protects heart tissue:

“It has been reported that dietary energy restriction, including intermittent fasting (IF), can protect heart and brain cells against injury and improve functional outcome in animal models of myocardial infarction (MI) and stroke. Here we report that IF improves glycemic control and protects the myocardium against ischemia-induced cell damage and inflammation in rats.”

The authors showed by echocardiographic analysis of heart structur and function that intermittent fasting attenuates the disease related increase in heart thickness, end systolic and diastolic volumes, and ejection fraction. Additionally…

“The size of the ischemic infarct 24 h following permanent ligation of a coronary artery was significantly smaller, and markers of inflammation (infiltration of leukocytes in the area at risk and plasma IL-6 levels) were less, in IF rats compared to rats on the control diet. IF resulted in increased levels of circulating adiponectin prior to and after MI.”

There is now a large body of evidence showing that ICR increases the protective hormone adiponectin much more than CCR. The authors conclude:

“Because recent studies have shown that adiponectin can protect the heart against ischemic injury, our findings suggest a potential role for adiponectin as a mediator of the cardioprotective effect of IF.”

A paper published in the journal Ageing Research Reviews discusses how IFR and CCR can protect the brain from accelerated neurodegeneration associated with aging. The authors note:

“The vulnerability of the nervous system to advancing age is all too often manifest in neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. In this review article we describe evidence suggesting that two dietary interventions, caloric restriction (CR) and intermittent fasting (IF), can prolong the health-span of the nervous system by impinging upon fundamental metabolic and cellular signaling pathways that regulate life-span.”

As we’ve seen regarding cardioprotection and tumorigenesis…

“CR and IF affect energy and oxygen radical metabolism, and cellular stress response systems, in ways that protect neurons against genetic and environmental factors to which they would otherwise succumb during aging. There are multiple interactive pathways and molecular mechanisms by which CR and IF benefit neurons including those involving insulin-like signaling, FoxO transcription factors, sirtuins and peroxisome proliferator-activated receptors. These pathways stimulate the production of protein chaperones, neurotrophic factors and antioxidant enzymes, all of which help cells cope with stress and resist disease.”

These studies comprise the first post that illustrates the scientific basis for the Lapis Light Weight Loss & Gene Modulation Program that customizes intermittent calorie restriction according to the individual’s weight management and other health needs. Subsequent posts will offer additional scientific evidence important for other aspects of the program.

What risk is there with airport full-body screening?

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A paper just published in the Archives of Internal Medicine puts the matter in perspective with a review of the science involved in analyzing risk associated with airport full-body scanners. The authors state:

“There are 2 types of full-body scanners in use. Each generates a detailed outline of the human body for the purpose of identifying contraband hidden under clothing. The millimeter-wave scanners emit extremely low-energy waves—each scan delivers a small fraction of the energy of a cell phone—and the scanners capture the reflected energy. The backscatter x-ray scanner, the type used more commonly in the United States, uses very low dose x-rays, similar to those used in medical imaging.”

The backscatter x-ray scanner is the type that has elicited the most concern. However…

“In contrast to x-rays used for medical imaging in which variation in the transmission of x-rays through the body is used to generate an image, backscatter scanners detect radiation that reflects off of the person imaged. When radiation passes through air, it deposits energy into the tissue that absorbs it, and with the backscatter technology, all of the energy of the scan is absorbed by the most superficial tissues of the body, such as the skin.”

In respect to the two linked but factors of dose and risk there is relevant evidence to consider:

“According to a recent report from the National Council on Radiation Protection and Measurements, individuals in the United States are exposed to an average of 6.2 millisieverts of ionizing radiation annually, or approximately 0.01 microsievert (µSv)/min. The 2 most common sources of exposure are medical procedures and ubiquitous background radiation, sometimes described as natural sources of radiation, including radiation from the sun and cosmic rays, and radiation from radon that is released from the earth. The backscatter x-ray scanners expose individuals to 0.03 to 0.1 µSv per scan or the equivalent to 3 to 9 minutes of radiation received from sources naturally occurring as part of daily living…The radiation associated with a flight will vary with altitude and latitude, but overall, air travel is associated with an exposure of approximately 0.04 µSv/min of flight time. The backscatter x-ray scans deliver radiation equivalent to around 1 to 3 minutes of flight time.“

Moreover…

“Put into context of the entire flight, if a woman embarks on a 6-hour flight, she will be exposed to approximately 14.3 µSv of radiation from the flight and 0.03 to 0.1 µSv from passing through the scanner at the airport. Thus, the scan will increase her exposure by less than 1%.”

To put this in further perspective:

“An individual would have to undergo more than 50 airport scans to equal the exposure of a single dental radiograph, 1000 airport scans to equal the exposure of a chest radiograph, 4000 airport scans to equal the exposure of a mammogram, and 200 000 airport scans to equal the exposure of a single abdominal and pelvic computed tomographic scan.”

Regarding the cancer risk posed by the use of airport full-body scanners…

“Estimating the risk associated with these extremely low dose exposures is more difficult than quantifying the exposure. Published studies that have demonstrated an association between radiation exposure and cancer risk have been performed at doses that are much higher than the levels emitted by the scans. To estimate the risk of these scans we must rely on extrapolation from these higher-dose studies, yet extrapolation of cancer risks from high doses to the exceedingly small doses of these scans is questionable and may be inappropriate.”

The authors selected 5 year old girls as a cohort to focus on for their analysis. They were chosen because…

“……children are more sensitive than adults to the effects of radiation, and we can use existing models to accurately estimate the risk of breast cancer from these scans…Several groups have developed models to allow estimation of the risk of cancer following exposure to ionizing radiation, and we used their estimate of an increase of approximately 0.08 cancers per sievert of exposure…”

When the data on 5 year old girls is entered into the equation here’s how it comes out:

“The breast dose for the backscatter scans is 0.049 µSv per scan, and the risk of breast cancer increases by 9140 cases per 100 000 five-year-old girls exposed to a sievert of radiation. We estimate that for every 2 million girls who travel 1 round trip per week, 1 additional breast cancer could occur from these scans over their lifetime. This increase of 1 cancer per 2 million young girls needs to be put in the context of the 250 000 breast cancers that will occur in these girls over the course of their lifetimes owing to the 12% lifetime incidence of breast cancer.”

The authors thus conclude:

“Based on what is known about the scanners, passengers should not fear going through the scans for health reasons, as the risks are truly trivial. If individuals feel vulnerable and are worried about the radiation emitted by the scans, they might reconsider flying altogether since most of the small, but real, radiation risk they will receive will come from the flight and not from the exceedingly small exposures from the scans.”

There is, however, a caveat associated with maintenance of the equipment:

“…if the machines do not function as provided, or if the settings are changed by employees after the machines are installed, or if they undergo software or mechanical errors or malfunctions, unknown effects could result…It would seem prudent for the TSA to permit additional testing to verify the safety of the devices.”

Pro-aging signaling, cancer and diabetes are reduced with LESS growth hormone effect

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Research just published in the journal Science Translational Medicine is a further reminder of the critical need  for caution and sound physiological thinking when considering the use of growth hormone. The authors note in their introduction:

“Reduced activity of growth hormone (GH) and insulin-like growth factor–1 (IGF-1) signaling proteins or of their orthologs in nonhuman organisms…contribute to extended life span and protection against age-dependent damage or diseases…”

Pursuant to these earlier observations they formulated an important investigative objective:

“Mutations in growth signaling pathways [that diminish the GH effect] extend life span, as well as protect against age-dependent DNA damage in yeast and decrease insulin resistance and cancer in mice. To test their effect in humans, we monitored for 22 years Ecuadorian individuals who carry mutations in the growth hormone receptor (GHR) gene that lead to severe GHR and IGF-1 (insulin-like growth factor–1) deficiencies.”

Combining this information with surveys that identified the cause and age of death for their subjects who died before this period, the data paint a compelling picture:

“The individuals with GHR deficiency exhibited only one nonlethal malignancy and no cases of diabetes, in contrast to a prevalence of 17% for cancer and 5% for diabetes in control subjects.“

They describe earlier studies that help explain the very low incidence of cancer. In one, serum from subjects with GHR deficiency had reduced DNA breakage yet increased apoptosis in human mammary epithelial cells treated with hydrogen peroxide. In others, serum from GHR-deficient subjects caused reduced expression of RAS, PKA (protein kinase A), and TOR (target of rapamycin) and up-regulation of SOD2 (superoxide dismutase 2) in treated cells. These changes in signaling promote cellular protection and life-span extension in model organisms.

Importantly, in their present study the authors also observed:

“……reduced insulin concentrations and a very low HOMA-IR (homeostatic model assessment–insulin resistance) index in individuals with GHR deficiency, indicating higher insulin sensitivity, which could explain the absence of diabetes in these subjects.”

These comments, along with an earlier post on growth hormone research, are a plea for caution along with sound thinking. There seem to be good reasons why we have evolved to reduce growth hormone activity with age. The authors advance the idea that blocking growth hormone receptor function may…

“…prevent or reduce the incidence of cancer, diabetes, and other age-related diseases, including inflammatory disorders, stroke, and neurodegenerative diseases.”

Clinicians and individuals tempted to experiment with growth hormone therapy should consider the authors’ conclusion:

“Our finding that human GHRD [growth hormone receptor deficient] subjects are protected against age-related pathologies is consistent with the elevated cellular protection in both yeast and human cells with reduced expression of specific pro-growth genes and with the effect of serum from GHRD subjects in lowering their expression. The results from the human cohort also show similarities with those from GHRD- and GH-deficient mice, which display lower incidence (49%) or delayed occurrence of fatal neoplasms and increased insulin sensitivity… These results provide evidence for a role of evolutionarily conserved pathways in the control of aging and disease burden in humans.”

Low cholesterol associated with higher mortality

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Most readers here are aware that cholesterol is the substrate for all steroid hormones and a component of all cell membranes, so that when too low it is a contributing factor to a range of disorders. A study just published in the Journal of Epidemiology provides more evidence for the association between low cholesterol and death from all causes. The authors state:

“We investigated the relationship between low cholesterol and mortality and examined whether that relationship differs with respect to cause of death.”

They conducted their study using 12,334 healthy adults from 12 rural areas in Japan. They correlated serum total cholesterol with total mortality, noting sex and cause of death. The average follow-up period was 11.9 years. What did their data show?

“As compared with a moderate cholesterol level (4.14-5.17 mmol/L)[161.5-201.5 mg/dL], the age-adjusted hazard ratio (HR) [risk] of low cholesterol (<4.14 mmol/L)[161.5 mg/dL] for mortality was 1.49 [50% increase in mortality]… High cholesterol (≥6.21 mmol/L)[≥242 mg/dL] was not a risk factor. This association was unchanged in analyses that excluded deaths due to liver disease… The multivariate-adjusted HRs [hazard ratios = risks]…of the lowest cholesterol group for hemorrhagic stroke, heart failure (excluding myocardial infarction), and cancer mortality [were] significantly higher than those of the moderate cholesterol group, for each cause of death.”

Numerous lines of reasoning, documented in a broad accumulation of scientific evidence (of which a small ‘taste’ is reported in this venue) converge on the assertion that inflammation, rather than cholesterol per se, is the primary villain in cardiovascular disease. Clinicians and patients alike should bear in mind the authors’ conclusion:

“Low cholesterol was related to high mortality even after excluding deaths due to liver disease from the analysis. High cholesterol was not a risk factor for mortality.“

Bioelectrical phase angle predicts quality of life and mortality with cancer

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Bioelectrical phase angle, which we easily and non-invasively measure in the clinic by bioelectrical impedance analysis, has been validated by numerous studies as a prognostic indicator for a variety of medical conditions. A study recently published in The American Journal of Clinical Nutrition offers evidence for its accuracy in predicting life quality, nutritional status and mortality for patients with cancer. The authors state:

“The bioelectrical phase angle has shown predictive potential in various diseases…This study evaluated the prognostic value of the fifth percentile of sex-, age-, and body mass index–stratified phase angle reference values in patients with cancer with respect to nutritional and functional status, quality of life, and 6-mo mortality.“

They then examined how the standardized phase angle and its deviation from population averages (‘z score’) on these life and mortality variables. They tested phase angle with bioelectical impedance analysis, muscle strength by handgrip and peak expiratory flow, employed assessments for quality of life and nutritional status, and documented survival after 6 months for 399 patients. What did the data show?

“Patients with a phase angle of less than the fifth reference percentile had significantly lower nutritional and functional status, impaired quality of life, and increased mortality. The standardized phase angle emerged as a significant predictor for malnutrition and impaired functional status in generalized linear model regression analyses. It was also a stronger indicator of 6-mo survival than were malnutrition and disease severity in the Cox regression model…”

Having an accurate, easy and inexpensive instrument to objectively evaluate the effectiveness of therapeutic case management in cancer in respect to mortality, function, quality of life and nutritional status is a resource that should not be overlooked by clinicians. The authors conclude:

“The standardized phase angle is an independent predictor for impaired nutritional and functional status and survival. The fifth phase angle reference percentile is a simple and prognostically relevant cutoff for detection of patients with cancer at risk for these factors.”

Note: This refers to bioelectrical impedance analysis measured by a professional clinical-grade instrument.

Cannabis suppresses the immune system

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A study just published in the European Journal of Immunology resolves how Cannabis sativa (marijuana) suppresses the immune system. The authors state:

“Cannabinoid receptor activation by agents such as Δ9-tetrahydrocannabinol (THC) is known to trigger immune suppression. Here, we show that administration of THC in mice leads to rapid and massive expansion of CD11b+Gr-1+ myeloid-derived suppressor cells (MDSC) expressing functional arginase and exhibiting potent immunosuppressive properties both in vitro and in vivo.”

Myeloid-derived suppressor cells (MDSC) are a class of white blood cells that act to regulate the immune system by suppressing immune activity. While their expansion can help to reduce the inflammation and pain of autoimmunity, in cancer they suppress immune system activity in the environment of a tumor. The authors further state:

“Use of selective antagonists SR141716A and SR144528 against cannabinoid receptors 1 and 2, respectively, as well as receptor-deficient mice showed that induction of MDSC was mediated through activation of both cannabinoid receptors 1 and 2. These studies demonstrate that cannabinoid receptor signaling may play a crucial role in immune regulation via the induction of MDSC.”

In other words, THC stimulates cannabinoid receptors 1 and 2 which triggered the proliferation of the immune suppressing MDSC. This is also likely to be at least part of the mechanism by which THC can cause an increase in susceptibility to opportunistic infections. Although this may be a rational therapy for organ transplantation where immune suppression is called for, it makes the use of marijuana worrisome for conditions where a deficient immune response needs support such as most cancers.

Most US doctors are still not paying proper attention to blood sugar

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It’s disturbing and worrisome to see how few doctors seem to be alert to the blood sugar dysregulation that precedes type 2 diabetes and many other chronic diseases in their patients as evidenced by a study just published in the journal Diabetes Care. The authors conducted their investigation to…

“…estimate the rates of prevalence, diagnosis, and treatment of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT).”

They examined a representative sample of the U.S. population that included 1,547 nondiabetic adults without a history of heart attack to determine the proportion who met the criteria for IFG/IGT, and the proportion of them who: 1) received a diagnosis from their physicians; 2) were prescribed lifestyle modification or medication for blood sugar; or 3) were currently on therapy. Their data painted a dismal picture:

“Of the 1,547 subjects, 34.6% had pre-diabetes; 19.4% had IFG only; 5.4% had IGT only, and 9.8% had both IFG and IGT. Only 4.8% of those with pre-diabetes reported having received a formal diagnosis from their physicians. No subjects with pre-diabetes received oral antihyperglycemics, and the rates of recommendation for exercise or diet were 31.7% and 33.5%, respectively.”

Yikes. It’s really up to the patient to be informed (one of the purposes of this blog) and seek proper care. Blood sugar dysregulation wrecks almost everything that clinicians practicing according to the functional model try to do to correct brain, hormone and immune dysregulation. It’s importance as a clinical focus is hard to over-emphasize. The authors’ disappointment is almost palpable in their conclusion:

“Three years after a major clinical trial demonstrated that interventions could greatly reduce progression from IFG/IGT to type 2 diabetes, the majority of the U.S. population with IFG/IGT was undiagnosed and untreated with interventions. Whether this is due to physicians being unaware of the evidence, unconvinced by the evidence, or clinical inertia is unclear.”

Perhaps this says something about why the scientists who authored another paper in the same issue of Diabetes Care saw fit to ask whether sugar-sweetened beverages would contribute to the risk of metabolic syndrome and type 2 diabetes (!):

“Consumption of sugar-sweetened beverages (SSBs), which include soft drinks, fruit drinks, iced tea, and energy and vitamin water drinks has risen across the globe. Regular consumption of SSBs has been associated with weight gain and risk of overweight and obesity, but the role of SSBs in the development of related chronic metabolic diseases, such as metabolic syndrome and type 2 diabetes, has not been quantitatively reviewed.”

Their meta-analysis included 310,819 participants from 11 acceptable studies. It’s troubling to allow that there may be physicians who might not anticipate the conclusion that their data defined:

“In addition to weight gain, higher consumption of SSBs is associated with development of metabolic syndrome and type 2 diabetes. These data provide empirical evidence that intake of SSBs should be limited to reduce obesity-related risk of chronic metabolic diseases.”

It seems that even fewer physicians and their patients are aware of the role of glucose in ‘feeding’ cancer and the research being done to block the metabolism of sugar by tumor cells as described in a paper just published in the journal Oncogene. The authors state:

“Tumors show an increased rate of glucose uptake and utilization. For this reason, glucose analogs are used to visualize tumors by the positron emission tomography technique, and inhibitors of glycolytic metabolism are being tested in clinical trials.”

While research investigates possible interventions to aggressively interrupt the glycolytic metabolism of tumor cells, doctors should assist their patients in controlling blood sugar and insulin (another tumor promoter) with the appropriate tools:

“Upregulation of glycolysis confers several advantages to tumor cells: it promotes tumor growth and has also been shown to interfere with cell death at multiple levels…Moreover, inhibition of glucose metabolism sensitizes cells to death ligands. Glucose deprivation and antiglycolytic drugs induce tumor cell death…”

Blood sugar dysregulation contributes to most chronic diseases including cardiovascular, autoimmune, neurodegenerative and malignant conditions. Supporting healthy blood sugar and insulin regulation is one of the most important things that practitioners and their patients can do together.

Elevated blood sugar increases risk of cancer

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A research article just published in PLoS (Public Library of Science) Medicine adds more evidence to the association between elevated blood sugar and cancer. The authors begin by stating:

“Prospective studies have indicated that elevated blood glucose levels may be linked with increased cancer risk…The aim of this study was to investigate the association between blood glucose and risk of incident and fatal cancer overall and at specific sites, as well as all-cause mortality, in a large study of six European cohorts including correction for random error in glucose levels..”

The Metabolic Syndrome and Cancer project (Me-Can) includes 274,126 men and 275,818 women from Norway, Austria and Sweden whose average age at the beginning of observation was 44.8 years. Over an average follow-up time of 10.4 years 18,621 men and 11,664 women were diagnosed with cancer, and 6,973 men and 3,088 women died of cancer. When the authors calculated the relative risk for glucose levels (adjusting for BMI and smoking), the data made a strong statement:

“Significant increases in risk among men were found for incident and fatal cancer of the liver, gallbladder, and respiratory tract, for incident thyroid cancer and multiple myeloma, and for fatal rectal cancer. In women, significant associations were found for incident and fatal cancer of the pancreas, for incident urinary bladder cancer, and for fatal cancer of the uterine corpus, cervix uteri, and stomach.”

The authors discuss the possible mechanisms:

“Insulin and bioavailable insulin-like growth factor-I (IGF-I) are possible links between glucose and cancer; hyperglycaemia induces elevation of these hormones that stimulate tumour growth. Glucose may also have a direct tumour-promoting effect as glucose is used as an energy substrate in tumour cells, particularly in fast-growing, highly proliferative tumour cells.”

They boil down their findings in this closing summary:

“In conclusion, abnormal glucose metabolism, independent of BMI, is associated with increases in risk of cancer and cancer death overall and at many specific sites. Furthermore, our data showed a linear and somewhat stronger association among women than among men, and the association was stronger for fatal compared to incident cancer.”

Angiotensin-receptor blockers for blood pressure linked to cancer

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If you are taking an angiotensin-receptor blocker (ARB) such as telmisartan (Micardis) or ramipril (Altace) it would be good to discuss changing to another medication in light of a serious risk factor for cancer brought to light in research published in the The Lancet Oncology. ARBs affect the renin-angiotensin system that regulates tension in the circulatory system; as the authors note:

“Experimental studies implicate the renin-angiotensin system, particularly angiotensin II type-1 and type-2 receptors, in the regulation of cell proliferation, angiogenesis, and tumour progression. We assessed whether ARBs affect cancer occurrence with a meta-analysis of randomised controlled trials of these drugs.”

They analyzed data from a number of trials involving tens of thousands of patients and came to this conclusion:

“This meta-analysis of randomised controlled trials suggests that ARBs are associated with a modestly increased risk of new cancer diagnosis.”

An accompanying editorial in the same issue expresses the gravity of this matter:

“The meta-analysis…is disturbing and provocative, raising crucial drug safety questions for practitioners and the regulatory community.”

Why use this class of medications when there is no evidence that they are more effective than others? A functional approach obviating the need for side-effect producing drugs is often successful if instituted early enough. While research data continues to accumulate about ARBs the author exhorts us to take this finding into serious and cautious consideration when determining the best approach to blood pressure for each person:

“In the interim, we should use ARBs, particularly telmisartan, with greater caution. These drugs are often overprescribed, as a result of aggressive marketing and in the absence of evidence that they are better than angiotensin-converting enzyme (ACE) inhibitors.”